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HypertensionHypertensionAn OverviewAn Overview
Dr. Devendra Khandke MDDr. Devendra Khandke MD
Head- Medical ServicesHead- Medical Services
Alembic LimitedAlembic Limited
What Is Blood Pressure ?What Is Blood Pressure ?
Blood pressure is the amount of Blood pressure is the amount of force on the walls of the arteries as force on the walls of the arteries as the blood circulates around the the blood circulates around the body.body.
BLOOD PRESSUREBLOOD PRESSURE
Systolic Blood pressure:Systolic Blood pressure:
- Pressure during systole- Pressure during systole
- The reading is higher- The reading is higher
Diastolic Blood pressure: Diastolic Blood pressure:
- Pressure during diastole- Pressure during diastole
- The reading is lower- The reading is lower
Blood PressureBlood Pressure
BP = pressure exerted on the vessel wall by BP = pressure exerted on the vessel wall by bloodblood
BP = BP = cardiac output ( CO)cardiac output ( CO) x x PVR PVR
where CO iswhere CO is
CO = stroke volume x Heart rateCO = stroke volume x Heart rate
BP = ( BP = ( SVSV X X HRHR ) X ) X PVRPVR
BLOOD PRESSUREBLOOD PRESSURE Peripheral Vascular Resistance depends on :Peripheral Vascular Resistance depends on :
- Lumen diameter of peripheral - Lumen diameter of peripheral arteriolesarterioles
- - dilatation of peripheral arterioles dilatation of peripheral arterioles decreases PVR & lowers BPdecreases PVR & lowers BP
- - Contraction of peripheral arterioles Contraction of peripheral arterioles increases PVR & BPincreases PVR & BP
BP:Diurnal variation
Blood PressureBlood Pressure
Two physiological systems which mainly controlTwo physiological systems which mainly control
blood pressure :blood pressure :
Sympathetic (SNS)Sympathetic (SNS) Autonomic Nervous SystemAutonomic Nervous System
(ANS)(ANS)
ParasympatheticParasympathetic
Renin-Angiotensin – Aldosterone – System Renin-Angiotensin – Aldosterone – System
(RAAS)(RAAS)
ANS:NeurotransmittersANS:Neurotransmitters
Sympathetic nervous sys:Sympathetic nervous sys:– NorepinephrineNorepinephrine– Epinephrine-released from adrenal Epinephrine-released from adrenal
medullamedulla
Parasympathetic nervous sys:Parasympathetic nervous sys:– AcetylcholineAcetylcholine
Blood PressureBlood PressureRole of SNS :Role of SNS : Neurotransmitters - Epinephrine Neurotransmitters - Epinephrine
(adrenaline) (adrenaline) Norepinephrine Norepinephrine (nor-adrenaline)(nor-adrenaline)
Adrenoceptors/ Adrenergic receptors - Adrenoceptors/ Adrenergic receptors - 11 (alpha) (alpha) 22
ββ11
ββ (Beta) (Beta)
ββ22
Main effect of Main effect of -adrenoceptors-adrenoceptors
OrganOrgan ReceptorReceptor Effect of Effect of stimulationstimulation
Blood vessels Blood vessels arterioles :arterioles :
1 Constriction – Constriction – increase in increase in PVRPVR
Main response mediated by Main response mediated by ββ-adrenoceptors-adrenoceptors
OrganOrgan β-ADRENOCEPTORSUBTYPE
RESPONSE TO STIMULATION
Heart β1 Increase in heart rate, and force of contraction
Kidney β1 Stimulation of renin release
Blood Vessels β2 Dilatation
Lung β2 Bronchodilatation
Glycogenolysis β1 (heart)β2 (skeletalmuscle, liver)
Promotes Glycogenolysis
Lipolysis (adipocytes)
β1 > β2 Promotes lipolysis
Sympathetic Nervous SystemSympathetic Nervous System SNS stimulation Release of neurotransmitters SNS stimulation Release of neurotransmitters
(Norepinephrine & (Norepinephrine & epinephrine)epinephrine)
They Combine with receptors (alpha & beta)They Combine with receptors (alpha & beta)
• Alpha receptors of blood vesselsAlpha receptors of blood vessels : :
vasoconstriction PVRvasoconstriction PVR
• Beta receptors of heartBeta receptors of heart : :
increase in heart rate, increase in force ofincrease in heart rate, increase in force of contraction contraction
Effect of SNS stimulationEffect of SNS stimulation
Heart rate (HR) Heart rate (HR) Cardiac Cardiac Force of contractionForce of contraction output output
Vasoconstriction - PVRVasoconstriction - PVR
Increase in BP
RAASRAAS
RENINAngiotensinogen Angiotensin I (Liver)
Angiotensin Converting
Enzyme Angiotensin II ( Active )
Major Actions: Major Actions: seen after combing with seen after combing with AT1 receptorsAT1 receptors
Most potent Vasoconstrictor-Most potent Vasoconstrictor-
- - Increase in PVRIncrease in PVR
Stimulates release of Aldosterone Stimulates release of Aldosterone
- - Sodium & Water retentionSodium & Water retention
Stimulates sympathetic Nervous Stimulates sympathetic Nervous
systemsystem
Angiotensin IIAngiotensin II
HypertensionHypertension
JNC-7JNC-7
Causes of HypertensionCauses of Hypertension Primary / Essential hypertension:Primary / Essential hypertension:
- No- No identifiable causeidentifiable cause– Most common causeMost common cause– Accounts for 93 % of cases Accounts for 93 % of cases
Secondary Hypertension:Secondary Hypertension:
(Due to other diseases)(Due to other diseases)– Renal HypertensionRenal Hypertension– Endocrine Hypertension etc.Endocrine Hypertension etc.
Harmful effects of High Blood PressureHarmful effects of High Blood Pressure
Hardening of the arteries-Hardening of the arteries-atherosclerosisatherosclerosis
StrokeStroke
Heart attackHeart attack
Kidney damage-kidney failureKidney damage-kidney failure
BlindnessBlindness
Target Organ Damage:Target Organ Damage:
HeartHeart - - CHF, MI CHF, MI
BrainBrain -- Stroke, Stroke,
Kidney - Renal failureKidney - Renal failure
Eyes -Eyes - Hypertensive RetinopathyHypertensive Retinopathy
Blood vessels Blood vessels - Atherosclerosis- Atherosclerosis
Complications of uncontrolled hypertensionComplications of uncontrolled hypertension
HypertensionHypertension
Important risk factor:Important risk factor:
- Myocardial infarction- Myocardial infarction
- Heart failure- Heart failure
- Stroke- Stroke
- Renal failure- Renal failure
Hypertension: MortalityHypertension: Mortality
HypertensionHypertension
A. Uncomplicated hypertension :A. Uncomplicated hypertension :
– Usually no symptomsUsually no symptoms
B. Complicated hypertension : B. Complicated hypertension :
Target organ damageTarget organ damageHeadacheHeadacheConfusionConfusionSevere shortness of breath etc.Severe shortness of breath etc.
Benefits of lowering BPBenefits of lowering BP
Condition Percent reductionStroke 34-40%
MI 20-25 %Heart Failure 50%
Goals of therapyGoals of therapy
BP < 140/90 mmHgBP < 140/90 mmHg
In diabetics or in patients with In diabetics or in patients with chronic renal disease:chronic renal disease:
<130/80 mmHg<130/80 mmHg
ISH : SBP in persons>50 years:ISH : SBP in persons>50 years: <140 mmHg<140 mmHg
Hypertension - ManagementHypertension - Management
Non- drug therapyNon- drug therapy
Drug therapyDrug therapy
Lifestyle modifications for Lifestyle modifications for hypertension controlhypertension control
Used as definitive or adjunctive therapy.Used as definitive or adjunctive therapy. Manage weight.Manage weight. Limit daily alcohol intake to Limit daily alcohol intake to 1 ounce of 1 ounce of
ethanol.ethanol. Engage in physical activity regularly.Engage in physical activity regularly. Reduce daily sodium intake to <2.3 grams of Reduce daily sodium intake to <2.3 grams of
sodium or <6 grams of sodium chloride.sodium or <6 grams of sodium chloride. Maintain adequate potassium, calcium, and Maintain adequate potassium, calcium, and
magnesium intake.magnesium intake. Stop smoking. Stop smoking. Reduce saturated fat and cholesterol intake.Reduce saturated fat and cholesterol intake.
Hypertension - ManagementHypertension - Management
Non - Pharmacological approach :Non - Pharmacological approach :
1. Relaxation techniques :1. Relaxation techniques :
Yoga, Meditation etcYoga, Meditation etc
2. 2. Regular ExerciseRegular Exercise
Lifestyle ModificationLifestyle Modification
ModificationModification Approximate SBP Approximate SBP reductionreduction(range)(range)
Weight reductionWeight reduction 5–20 mmHg/10 kg weight loss5–20 mmHg/10 kg weight loss
Adopt DASH eating planAdopt DASH eating plan 8–14 mmHg8–14 mmHg
Dietary sodium reductionDietary sodium reduction 2–8 mmHg2–8 mmHg
Physical activityPhysical activity 4–9 mmHg4–9 mmHg
Moderation of alcohol Moderation of alcohol consumptionconsumption
2–4 mmHg2–4 mmHg
Ideal Antihypertensive drugIdeal Antihypertensive drug
Good efficacy-should provide Good efficacy-should provide 24-hr control24-hr control
of BP with once daily doseof BP with once daily dose
Minimal or no serum glucose imbalanceMinimal or no serum glucose imbalance
Minimal or no electrolyte imbalanceMinimal or no electrolyte imbalance
Minimal or no lipid profile imbalanceMinimal or no lipid profile imbalance
Improve quality of life Improve quality of life
- Physical activity, sleep, sexual - Physical activity, sleep, sexual
functions.functions.
Dosage complianceDosage compliance
Major AntihypertensivesMajor Antihypertensives
1. Diuretics: Hydrochlorothiazide1. Diuretics: Hydrochlorothiazide
2. Beta blockers : Atenolol,nebivolol,metoprolol2. Beta blockers : Atenolol,nebivolol,metoprolol
3.3. ACE inhibitors :ACE inhibitors :
- Enalapril, Lisinopril, Ramipril etc- Enalapril, Lisinopril, Ramipril etc
4. AT1 receptor antagonists:4. AT1 receptor antagonists:
- Losartan,valsartan,telmisartan etc- Losartan,valsartan,telmisartan etc
5.5. Calcium antagonists : Calcium antagonists :
- Amlodipine, Nifedipine, Diltiazem- Amlodipine, Nifedipine, Diltiazem
6.6. Alpha blockers :Alpha blockers :
- - Prazosin,terazosin,doxazosinPrazosin,terazosin,doxazosin
DiureticsDiuretics Act onAct on kidneyskidneys-Increase excretion of -Increase excretion of
sodium & watersodium & water
Reduce Blood Volume Reduce Blood Volume [ Preload ][ Preload ]
• Reduce BP
Thiazide DiureticsThiazide Diuretics
First-line treatment in mildFirst-line treatment in mild
( Stage 1 ) hypertension( Stage 1 ) hypertension
Often used in combination with other Often used in combination with other
antihypertensive agents -antihypertensive agents -
e.g. ACEIs, ATe.g. ACEIs, AT11 lockers, lockers,
beta blockersbeta blockers
DiureticsDiuretics
IndicationsIndications
HypertensionHypertension
Heart failureHeart failure
Beta BlockersBeta Blockers Mode of actionMode of action
Block Beta receptors present in heart :Block Beta receptors present in heart :
Decrease CO-decrease heart rate & force of Decrease CO-decrease heart rate & force of
contraction-contraction-negative chronotropic & negative chronotropic &
negative inotropic effectsnegative inotropic effects
Decrease in Renin release from the KidneysDecrease in Renin release from the Kidneys
Central action - reduction in Sympathetic Central action - reduction in Sympathetic
tonetone
Beta blockersBeta blockersClassification :Classification :
1.1.Non-selective:Non-selective:
Block both Block both beta1beta1 & & beta2beta2 receptors receptors
(Propranolol )(Propranolol )
2.2.Cardio-selectiveCardio-selective::
Block only beta1 receptors Block only beta1 receptors (Atenolol,Metoprolol,Nebivolol )(Atenolol,Metoprolol,Nebivolol )
3. 3. Combined beta & alpha blockerCombined beta & alpha blocker::
Block both beta1 & beta2 + alpha1 receptors Block both beta1 & beta2 + alpha1 receptors
( ( carvedilolcarvedilol ) )
Beta BlockersBeta Blockers IndicationsIndications
HypertensionHypertension AnginaAngina Post-MIPost-MI
Beta BlockersBeta Blockers
Side effectsSide effectsBradycardiaBradycardiaAV block- not safe in heart blockAV block- not safe in heart blockFatigueFatigueBronchospasm- not safe in Bronchospasm- not safe in asthmaasthma
Loss of LibidoLoss of LibidoImpotenceImpotenceDyslipidemiaDyslipidemia
Calcium AntagonistsCalcium Antagonists Also called calcium channel blockers-Dialate Also called calcium channel blockers-Dialate
arterioles- decrease PVR & BParterioles- decrease PVR & BP 3 groups:3 groups:
1.1.Dihydropyridine derivatives:Dihydropyridine derivatives: Nifedipine,felodipine,amlodipine etcNifedipine,felodipine,amlodipine etc
22.Benzothiazepines: Diltiazem.Benzothiazepines: Diltiazem
3.3.Phenylalkylamines:Phenylalkylamines: VerapamilVerapamil
CCBsCCBs block the L type calcium channels block the L type calcium channels present within blood vessels- present within blood vessels- prevent entry prevent entry of calcium ions into vascular smooth muscle of calcium ions into vascular smooth muscle fibersfibers
– relaxing large and small arteries and relaxing large and small arteries and
reducing peripheral resistancereducing peripheral resistance( PVR )( PVR )
– Reduce force of contraction of Reduce force of contraction of myocardiummyocardium
Calcium Antagonists
Calcium Channel BlockersCalcium Channel Blockers
IndicationsIndications
– HypertensionHypertension
– AnginaAngina
CCBs are commonly used to treat hypertension CCBs are commonly used to treat hypertension because:because:
– Very well tolerated,compliance is high, Very well tolerated,compliance is high,
– They don’t have any adverse effect on quality They don’t have any adverse effect on quality of lifeof life
– Do not alter carbohydrate or lipid MetabolismDo not alter carbohydrate or lipid Metabolism
– often used in combination with beta-blocker often used in combination with beta-blocker therapy therapy
Calcium antagonists
Contraindications:Contraindications:– Acute MIAcute MI– Heart failureHeart failure
Averse Drug Reactions:Averse Drug Reactions:– FlushingFlushing– HeadacheHeadache– Ankle oedemaAnkle oedema– Reflex tachycardiaReflex tachycardia
Calcium antagonists
ACE InhibitorsACE Inhibitors Inhibit Angiotensin Converting Inhibit Angiotensin Converting
EnzymeEnzyme
Decrease formation of angiotensin IIDecrease formation of angiotensin II
- - decrease afterload & preloaddecrease afterload & preload
Lower BPLower BP
Examples:Examples: CaptoprilCaptoprilEnalaprilEnalaprilLisinoprilLisinoprilBenazeprilBenazeprilPerindoprilPerindoprilRamiprilRamipril
ACE InhibitorsACE Inhibitors
Indications:Indications:
HypertensionHypertension
Heart failureHeart failure
Post MIPost MI
Diabetic NephropathyDiabetic Nephropathy
ACE InhibitorsACE Inhibitors
Adverse effects:Adverse effects:
HyperkalemiaHyperkalemia Dry coughDry cough
Less common:Less common: RashRash
ACE InhibitorsACE Inhibitors
Contraindications :Contraindications :
Bilateral renal artery Bilateral renal artery
stenosisstenosis
Severe renal failureSevere renal failure
PregnancyPregnancy
lactationlactation
ACE InhibitorsACE Inhibitors
Block the ATBlock the AT1 1 receptors receptors
Reduce afterload & preloadReduce afterload & preload
e.g. Losartan, candesartan, valsartan,e.g. Losartan, candesartan, valsartan,
telmisartan etctelmisartan etc
Better tolerated than ACE inhibitors-Better tolerated than ACE inhibitors-
- do not produce dry cough- do not produce dry cough
Angiotensin-II Receptor BlockersAngiotensin-II Receptor Blockers
Diabetic hypertensiveDiabetic hypertensive
70 % of Type 2 diabetics have hypertension70 % of Type 2 diabetics have hypertension
Co-existing diabetes & hypertension Co-existing diabetes & hypertension increases risk of renal diseaseincreases risk of renal disease Target BP : <130/80 mmHgTarget BP : <130/80 mmHg Drugs of choiceDrugs of choice: ACEIs,ARBs,CCBs: ACEIs,ARBs,CCBs
Benefits : Benefits : Greater reduction in cardiovascular Greater reduction in cardiovascular events e.g. MI, deathevents e.g. MI, death Slower decline in renal functionSlower decline in renal function
Hypertension with heart failureHypertension with heart failure
ACE-I or ARBACE-I or ARB
Add diuretic if- not controlled or water retentionAdd diuretic if- not controlled or water retention
Additional therapy: carvedilol or MetoprololAdditional therapy: carvedilol or Metoprolol
Smoking Beta-blocker
The benefits of treatingsmokers with beta-blockers
remain uncertainin the absence
of a specific indicationlike angina or post-MI
Treatment of Hypertension With Treatment of Hypertension With Associated Risk Factors Associated Risk Factors
Drug of choice : CCB
Treatment of Hypertension Treatment of Hypertension
with Airways Diseases*with Airways Diseases*
Airway disease*
Standard HTN treatment.If thiazide, add
potassium-sparing diuretic
Beta-blocker
Calcium channel blocker
All Beta-blockers arecontraindicated if asthma
or bronchial hyperreactivity
* Asthma, COPD
Hypertension with IHD/ CADHypertension with IHD/ CAD
Stable angina
Post - MI
Beta blocker or CCB
Beta blocker or ACE-I
Isolated Systolic Hypertension :Isolated Systolic Hypertension :
Most common type of hypertension seen in the Most common type of hypertension seen in the
elderlyelderly
Prevalence:Prevalence: 5% in populations aged 60-69yrs 5% in populations aged 60-69yrs
10% in populations aged 70-79 yr.10% in populations aged 70-79 yr.
Cause:Cause: Rigidity & loss of elasticity of large Rigidity & loss of elasticity of large
arteries.arteries.
Isolated Systolic hypertension ( ISH)Isolated Systolic hypertension ( ISH)
Systolic BP > 140 mm HgSystolic BP > 140 mm Hg
Diastolic BP < 90 mm HgDiastolic BP < 90 mm Hg
Common in elderlyCommon in elderly
Increased risk of MI,stroke & Increased risk of MI,stroke &
cardiovascular mortalitycardiovascular mortality
Treatment:Treatment: Calcium channel blockers Calcium channel blockers
DiureticsDiuretics
Initial Drug Choices
Without Compelling indication: Thiazide-Type Diuretics (or ACEI, ARB, BB, CCB)
Treatment ofTreatment ofHypertensionHypertension
Not at Goal Blood Pressure (<140/90 mmHg) (<130/80 mmHg for those with diabetes or chronic kidney disease)
Initial Drug Choices
Drug(s) for the compelling indications
Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB)
as needed.
With Compelling Indications
Lifestyle Modifications
Stage 2 Hypertension (SBP >160 or DBP >100 mmHg)
2-drug combination for most (usually thiazide-type diuretic and
ACEI, or ARB, or BB, or CCB)
Stage 1 Hypertension(SBP 140–159 or DBP 90–99
mmHg) Thiazide-type diuretics for most.
May consider ACEI, ARB, BB, CCB,
or combination.
Without Compelling Indications
Not at Goal Blood Pressure
Optimize dosages or add additional drugs until goal blood pressure is achieved.
Algorithm for Treatment of HypertensionAlgorithm for Treatment of Hypertension
Stage 2 Hypertension (SBP >160 or DBP >100 mmHg)
2-drug combination for most (usually thiazide-type diuretic and
ACEI, or ARB, or BB, or CCB)
Stage 2 Hypertension (SBP >160 or DBP >100 mmHg)
2-drug combination for most
(usually thiazide-type diuretic and ACEI, or ARB, or BB, or CCB)
Guidelines: Hypertension Prevention Guidelines: Hypertension Prevention and Management -- JNC 7and Management -- JNC 7
For patients 50 and older, elevated systolic BP is a For patients 50 and older, elevated systolic BP is a better indicator of cardiovascular risk than elevated better indicator of cardiovascular risk than elevated diastolic BPdiastolic BP
Normal BP is defined as SBP <120 mm Hg and DBP <80 Normal BP is defined as SBP <120 mm Hg and DBP <80 mm Hgmm Hg
Within the BP range of 115/75 to 185/115 mm Hg, each Within the BP range of 115/75 to 185/115 mm Hg, each increment of 20/10 mm Hg doubles cardiovascular riskincrement of 20/10 mm Hg doubles cardiovascular risk
Lifestyle modification for all patients with Lifestyle modification for all patients with prehypertension and drug therapy only for prehypertension and drug therapy only for prehypertensive patients with "compelling indications" prehypertensive patients with "compelling indications" (heart failure, prior MI, high CHD risk, diabetes, chronic (heart failure, prior MI, high CHD risk, diabetes, chronic kidney disease, prevention of recurrent stroke)kidney disease, prevention of recurrent stroke)
Guidelines: Hypertension Prevention Guidelines: Hypertension Prevention and Management -- JNC 7and Management -- JNC 7
BP-control target is <140/<90 mm Hg, except in BP-control target is <140/<90 mm Hg, except in patients with diabetes or renal disease, whose target patients with diabetes or renal disease, whose target is <130/<80 mm Hgis <130/<80 mm Hg
Prevention and treatment should begin with multiple Prevention and treatment should begin with multiple lifestyle modificationslifestyle modifications
Thiazide-type diuretics -- either alone or in Thiazide-type diuretics -- either alone or in combination with ACE inhibitors, angiotensin-receptor combination with ACE inhibitors, angiotensin-receptor blockers, beta-blockers, or calcium-channel blockers -- blockers, beta-blockers, or calcium-channel blockers -- should be initial drug therapy for most patients with should be initial drug therapy for most patients with uncomplicated hypertension uncomplicated hypertension
Hypertensive patients with compelling indications start Hypertensive patients with compelling indications start with another drug class, specific to the compelling with another drug class, specific to the compelling conditioncondition
Guidelines: Hypertension Prevention Guidelines: Hypertension Prevention and Management -- JNC 7and Management -- JNC 7
Most hypertensive patients will require at least 2 BP-Most hypertensive patients will require at least 2 BP-lowering medications to achieve BP goals. lowering medications to achieve BP goals.
If a patient is more than 20/10 mm Hg above goal, the If a patient is more than 20/10 mm Hg above goal, the authors recommend that clinicians consider initiating authors recommend that clinicians consider initiating therapy with 2 drugs.therapy with 2 drugs.
Because adherence to antihypertensive treatment is Because adherence to antihypertensive treatment is generally poor, a clearly articulated, patient-centered generally poor, a clearly articulated, patient-centered BP-control approach with diligent monitoring is BP-control approach with diligent monitoring is importantimportant
Renin –Angiotensin – Aldosterone Renin –Angiotensin – Aldosterone System (RAAS)System (RAAS)
Plays an essential role in regulation of Plays an essential role in regulation of
blood pressure, blood volume, blood pressure, blood volume,
electrolyte balance and glomerular electrolyte balance and glomerular
filtration rate (GFR)filtration rate (GFR)
RAASRAASAngiotensinogenAngiotensinogen
Renin(kidney)Renin(kidney)
Angiotensin IAngiotensin I
Non ACE ACENon ACE ACE PathwayPathway
Angiotensin IIAngiotensin II
ATAT11 receptors AT receptors AT22 receptors receptors
Vasoconstriction Aldosterone Stimulation Cell Vasoconstriction Aldosterone Stimulation Cell growthgrowth
(PVR)(PVR) release of SNS release of SNS salt & watersalt & water retention retention (preload)(preload)
RAASRAAS
RAASRAAS Renin Renin
– An enzyme synthesized and released by the An enzyme synthesized and released by the
juxtaglomerular cells of the kidneysjuxtaglomerular cells of the kidneys
– Acts on Acts on AngiotensinogenAngiotensinogen
– Converts angiotensinogen to Angiotensin IConverts angiotensinogen to Angiotensin I
AngiotensinogenAngiotensinogen Angiotensin - I Renin
RAASRAAS
Angiotensin IAngiotensin I Angiotensin II (A II) ACE
Functions of ACE:
Conversion of Angiotensin I to Angiotensin II
Degradation of bradykinin
Bradykinin Inactive ingredientsACE
RAASRAAS
Angiotensin II is highly active Angiotensin II is highly active
Produces a number of effects in different Produces a number of effects in different
parts of the body after combining with parts of the body after combining with
Angiotensin II receptorAngiotensin II receptor
ATAT11 and AT and AT22 receptors receptors
RAASRAAS
ATAT11 receptors: receptors:
– Responsible for virtually all the known Responsible for virtually all the known
actions of Angiotensin II actions of Angiotensin II
ATAT11 receptors are present in the receptors are present in the
– blood vesselsblood vessels
– adrenal glandadrenal gland
– heartheart
– kidney kidney
– brain & brain &
– liverliver
RAASRAAS Vasoconstriction:Vasoconstriction:
– Angiotensin II is the most potent Angiotensin II is the most potent
vasoconstrictor in the body vasoconstrictor in the body
– Produces constriction of arterioles as Produces constriction of arterioles as
well as veinswell as veins
– Constriction of peripheral arterioles Constriction of peripheral arterioles
results in increased Peripheral results in increased Peripheral
Vascular Resistance (PVR)Vascular Resistance (PVR)
RAASRAAS Aldosterone releaseAldosterone release
Angiotensin IIAngiotensin II
Aldosterone release from adrenal glandAldosterone release from adrenal gland
Retention of sodium & waterRetention of sodium & water
Increase in blood volume (Preload)Increase in blood volume (Preload)
RAASRAAS
– Stimulation of sympathetic nervous Stimulation of sympathetic nervous system, which leads to increased release system, which leads to increased release of norepinephrineof norepinephrine
– Stimulates the release of antidiuretic Stimulates the release of antidiuretic hormone, ADH from the posterior pituitary, hormone, ADH from the posterior pituitary, which increases fluid retention by the which increases fluid retention by the kidneyskidneys
– Stimulates thirst centers within the brain Stimulates thirst centers within the brain
Aldosterone release
RAASRAAS
Trophic action (Proliferative action):Trophic action (Proliferative action):
– Angiotensin II leads to proliferation of Angiotensin II leads to proliferation of
cardiac myocytes cardiac hypertrophy cardiac myocytes cardiac hypertrophy
vascular smooth muscle cells vascular vascular smooth muscle cells vascular
hypertrophyhypertrophy
RAASRAAS
RAASRAAS Inappropriately elevated levels of angiotensin II have Inappropriately elevated levels of angiotensin II have
following adverse effects:following adverse effects:
– Constriction of peripheral arterioles leads to Constriction of peripheral arterioles leads to increased PVR (afterload)increased PVR (afterload)
– Angiotensin II leads to aldosterone secretion from Angiotensin II leads to aldosterone secretion from adrenal cortexadrenal cortex
– Aldosterone causes sodium & water retention in the Aldosterone causes sodium & water retention in the body, thus increasing blood volume (preload)body, thus increasing blood volume (preload)
RAASRAAS Inappropriately elevated levels of angiotensin II have Inappropriately elevated levels of angiotensin II have
following adverse effects:following adverse effects:
– Angiotensin II stimulates sympathetic nervous Angiotensin II stimulates sympathetic nervous system results in increased blood levels of system results in increased blood levels of norepinephrine & epinephrinenorepinephrine & epinephrine
– Angiotensin II has trophic action on the heart, Angiotensin II has trophic action on the heart, kidneys & blood vesselskidneys & blood vessels
RAASRAAS
Excessive activation of the RAAS Excessive activation of the RAAS
plays an important role in the plays an important role in the
pathophysiology of hypertension, pathophysiology of hypertension,
heart failure & diabetic heart failure & diabetic
nephropathynephropathy
RAASRAAS
All these actions of angiotensin II All these actions of angiotensin II
are seen after it has combined are seen after it has combined
with ATwith AT11 receptors receptors
RAASRAAS
Harmful effects of angiotensin II can be Harmful effects of angiotensin II can be
prevented by two different ways :prevented by two different ways :
– By decreasing formation of angiotensin II By decreasing formation of angiotensin II
from angiotensin I- through inhibition of ACE from angiotensin I- through inhibition of ACE
– By blocking the ATBy blocking the AT11 receptors - As a result receptors - As a result
angiotensin II is not in a position to combine angiotensin II is not in a position to combine
with ATwith AT11 receptors receptors
RAAS - InhibitionRAAS - Inhibition
Two different groups of drugs that Two different groups of drugs that
inhibit the RAAS are:inhibit the RAAS are:
– ACE inhibitors e.g. Enalapril, Lisinopril, ACE inhibitors e.g. Enalapril, Lisinopril,
Ramipril Ramipril
– ATAT11 receptor blockers (ARBs) e.g. receptor blockers (ARBs) e.g.
Losartan, Valsartan, Telmisartan Losartan, Valsartan, Telmisartan
RAAS - InhibitionRAAS - Inhibition
PARAMETERPARAMETER ACE INHIBITORSACE INHIBITORS AT1RECEPTOR BLOCKERSAT1RECEPTOR BLOCKERS
Inhibition of RAASInhibition of RAAS Incomplete ( Partial)Incomplete ( Partial) CompleteComplete
Effect on blood levels of Effect on blood levels of AIIAII
DecreasedDecreased No changeNo change
Effect on blood levels of Effect on blood levels of bradykininbradykinin
IncreasedIncreased No changeNo change
TolerabilityTolerability PoorPoor(Dry cough, (Dry cough, angioedema)angioedema)
BetterBetter( No dry cough)( No dry cough)
Tellzy Tellzy (Telmisartan 20, 40, 80 mg (Telmisartan 20, 40, 80 mg
tablets)tablets)
Novel ATNovel AT11 receptor receptor antagonistantagonist
Tellzy Tellzy
DescriptionDescription
TELLZY (telmisartan) is an TELLZY (telmisartan) is an
angiotensin II receptor antagonist angiotensin II receptor antagonist
that is highly selective for Type1 that is highly selective for Type1
angiotensin II receptorsangiotensin II receptors
TelmisartanTelmisartan
Mechanism Of actionMechanism Of action
Telmisartan prevents the effects of angiotensin II by Telmisartan prevents the effects of angiotensin II by selectively blocking the binding of angiotensin II to the ATselectively blocking the binding of angiotensin II to the AT11 receptors in many tissues, such as receptors in many tissues, such as – vascular smooth musclevascular smooth muscle– adrenal glandadrenal gland
Its action is therefore independent of the pathways for Its action is therefore independent of the pathways for angiotensin II synthesisangiotensin II synthesis
Telmisartan produces more complete inhibition of RAAS as Telmisartan produces more complete inhibition of RAAS as compared to ACE inhibitorscompared to ACE inhibitors
TelmisartanTelmisartan
Mechanism Of actionMechanism Of action
Highly selective ATHighly selective AT11 receptor blocker receptor blocker
High affinity for ATHigh affinity for AT11 receptors receptors
Prevents binding of Angiotensin II with ATPrevents binding of Angiotensin II with AT11 receptors receptors
Blocks action of angiotensin II
Lowers PVR and preload- lowering of BP
TelmisartanTelmisartan Anti-hypertensive action: Anti-hypertensive action:
– Following once daily administration of telmisartan, Following once daily administration of telmisartan,
the magnitude of blood pressure reduction from the magnitude of blood pressure reduction from
baseline was approximately (SBP/DBP) baseline was approximately (SBP/DBP)
– 6-8/6 mmHg for 20 mg6-8/6 mmHg for 20 mg
– 9-13/6-8 mmHg for 40 mg9-13/6-8 mmHg for 40 mg
– 12-13/7-8 mmHg for 80 mg12-13/7-8 mmHg for 80 mg
TelmisartanTelmisartan
There were no changes in the heart rate of There were no changes in the heart rate of
patients treated with telmisartanpatients treated with telmisartan
Unlike dihydropyridine CCBs, telmisartan Unlike dihydropyridine CCBs, telmisartan
doesn’t produce reflex tachycardia doesn’t produce reflex tachycardia
TelmisartanTelmisartan
Additional Beneficial Metabolic effects: Additional Beneficial Metabolic effects:
– Telmisartan is a partial agonist of PPAR – γ (perioxisome Telmisartan is a partial agonist of PPAR – γ (perioxisome
proliferators activated receptor γ), that plays a role in the proliferators activated receptor γ), that plays a role in the
regulation of carbohydrate and lipid metabolismregulation of carbohydrate and lipid metabolism
Improves insulin sensitivityImproves insulin sensitivity
Decreases adipocyte cell sizeDecreases adipocyte cell size
Decrease hepatic fat storageDecrease hepatic fat storage
TelmisartanTelmisartan
Telmisartan treatment results in improvements in Telmisartan treatment results in improvements in
lipid profiles and insulin sensitivity in lipid profiles and insulin sensitivity in
hypertensive patients with co-existing type 2 hypertensive patients with co-existing type 2
diabetesdiabetes
TelmisartanTelmisartan
PharmacokineticsPharmacokinetics
– Rapidly absorbed ( TRapidly absorbed ( Tmaxmax :1hr) :1hr)
– Bioavailability : 50%Bioavailability : 50%
– Steady state achieved within : 5-7 daysSteady state achieved within : 5-7 days
– Metabolized in liver- inactive metabolitesMetabolized in liver- inactive metabolites
– Mean elimination half life: 24 hrsMean elimination half life: 24 hrs
– Main route of excretion: feaces ( > 90 %)Main route of excretion: feaces ( > 90 %)
Long Terminal Half LifeLong Terminal Half Life
Pharmacokinetic evaluation of telmisartan in mild Pharmacokinetic evaluation of telmisartan in mild to-moderate hypertensive patients showed a to-moderate hypertensive patients showed a terminal half life of ~ 24 hterminal half life of ~ 24 h
Long terminal half-life supports a once-daily Long terminal half-life supports a once-daily dosing regimen and suggests that drug dosing regimen and suggests that drug concentrations do not decline below therapeutic concentrations do not decline below therapeutic levels even if a dose is delayedlevels even if a dose is delayed
Expert Opin. Pharmacother. (2008) 9(8):1397-1406
9
5-9
11-15
2.5-910-15
24
9
0 5 10 15 20 25
Telmisartan has long half life : 24 hours
Valsartan
Telmisartan
Olmesartan
Losartan
Irbesartan
Eprosartan
Candesartan
Goodman & Gilman p 812-813 11th edition
Telmisartan- Unique propertiesTelmisartan- Unique properties
Greater affinity (>3,000 fold) for the ATGreater affinity (>3,000 fold) for the AT11
receptors than for the ATreceptors than for the AT22 receptors receptors
Highly lipophilic in nature therefore it has Highly lipophilic in nature therefore it has
better tissue penetration & it provides greater better tissue penetration & it provides greater
inhibition of tissue RAASinhibition of tissue RAAS
Telmisartan- Unique propertiesTelmisartan- Unique properties
Longer elimination half lifeLonger elimination half life
After binding with ATAfter binding with AT11 receptors, it dissociates very slowly receptors, it dissociates very slowly
[dissociation half-life 5.9 hours] ensures prolonged [dissociation half-life 5.9 hours] ensures prolonged
antihypertensive action of telmisartanantihypertensive action of telmisartan
As a result once daily dose of telmisartan provides 24 hrs As a result once daily dose of telmisartan provides 24 hrs
control of blood pressurecontrol of blood pressure
BP control is sustained through out the 24 hour dosage BP control is sustained through out the 24 hour dosage
interval, including during the last 6 hours of the periodinterval, including during the last 6 hours of the period
Telmisartan- Unique propertiesTelmisartan- Unique properties
Highly lipophilic- better tissue penetration- Highly lipophilic- better tissue penetration-
better inhibition of tissue RAS.better inhibition of tissue RAS.
Slow dissociation from ATSlow dissociation from AT11 receptors receptors
Long elimination half life :24 hrsLong elimination half life :24 hrs
24 hrs blood pressure lowering effect
Telmisartan- Unique propertiesTelmisartan- Unique properties
ADDITIONAL BENEFICIAL METABOLIC EFFECTS:ADDITIONAL BENEFICIAL METABOLIC EFFECTS:
Majority of the patients with hypertension have other Majority of the patients with hypertension have other features of the metabolic syndrome like:features of the metabolic syndrome like:
– Abdominal ObesityAbdominal Obesity– DyslipidemiaDyslipidemia– Insulin resistanceInsulin resistance
Telmisartan treatment results in improvements in lipid Telmisartan treatment results in improvements in lipid profiles and insulin sensitivity in hypertensive patients with profiles and insulin sensitivity in hypertensive patients with co-existing type 2 diabetesco-existing type 2 diabetes
Telmisartan- Unique propertiesTelmisartan- Unique properties
High Trough to Peak Ratio – better control of BPHigh Trough to Peak Ratio – better control of BP
The patients on telmisartan experienced greater The patients on telmisartan experienced greater
regression of LVHregression of LVH
Mean treatment compliance rate was 98.6 to 99.9 %Mean treatment compliance rate was 98.6 to 99.9 %
Telmisartan- AdvantagesTelmisartan- Advantages
Longer elimination half-life of 24 hrsLonger elimination half-life of 24 hrs
High affinity towards ATHigh affinity towards AT11 receptor (telmisartan > receptor (telmisartan >
olmesartan > candesartan olmesartan > candesartan >> valsaratan valsaratan >> losartan) losartan)
Very slow dissociation rateVery slow dissociation rate
These unique properties of Telmisartan ensure
improved 24- hr control of blood pressure as
compared to other ARBs
Telmisartan- AdvantagesTelmisartan- Advantages
Unlike other once a day ARBs, which fall short of
providing good antihypertensive action for 4 to 6
hours before the next morning dose is
administrated, Telmisartan has demonstrated better
BP lowering effect in predosing hours
24-hour action of Telmisartan covers the early
morning risk- hours, when the need for the BP
control is the greatest
TellzyTellzy INDICATIONSINDICATIONS
– TELLZY (telmisartan) is indicated for the treatment of TELLZY (telmisartan) is indicated for the treatment of hypertensionhypertension
– US FDA has approved it for the reduction of the risk US FDA has approved it for the reduction of the risk of myocardial infarction (heart attack), stroke, or of myocardial infarction (heart attack), stroke, or death from cardiovascular (CV) causes in patients 55 death from cardiovascular (CV) causes in patients 55 years of age or older at high risk of developing major years of age or older at high risk of developing major CV events who are unable to take ACE inhibitorsCV events who are unable to take ACE inhibitors
– European Commission has approved telmisartan for European Commission has approved telmisartan for the reduction of cardiovascular morbidity in patients the reduction of cardiovascular morbidity in patients with: with: I. manifest atherothrombotic cardiovascular disease I. manifest atherothrombotic cardiovascular disease (history of coronary heart disease, stroke, or (history of coronary heart disease, stroke, or peripheral arterial disease) or, peripheral arterial disease) or, II. type 2 diabetes mellitus with documented target II. type 2 diabetes mellitus with documented target organ damage.organ damage.
Telmisartan is the first treatment in its class to be approved for this indication.
TellzyTellzy
DOSAGE AND ADMINISTRATIONDOSAGE AND ADMINISTRATION
– Usual starting dose of Telmisartan tablets is 20 mg once a dayUsual starting dose of Telmisartan tablets is 20 mg once a day
– If required, its dose may be increased to 40mg after 2-4 wksIf required, its dose may be increased to 40mg after 2-4 wks
– Maximum antihypertensive effect is generally attained 4 to 8 Maximum antihypertensive effect is generally attained 4 to 8
weeks after the start of therapyweeks after the start of therapy
– Maximum recommended dose is 80mg/ dayMaximum recommended dose is 80mg/ day
– When additional blood pressure reduction beyond that achieved When additional blood pressure reduction beyond that achieved
with 80 mg Telmisartan is required, a diuretic with 80 mg Telmisartan is required, a diuretic
(Hydrochlorothiazide) may be added(Hydrochlorothiazide) may be added
TellzyTellzy
DOSAGE AND ADMINISTRATIONDOSAGE AND ADMINISTRATION
– No dose adjustment required in elderly or in renal No dose adjustment required in elderly or in renal
impairmentimpairment
– Use with caution in hepatic dysfunction- dose Use with caution in hepatic dysfunction- dose
should not exceed 40 mg /dayshould not exceed 40 mg /day
– Safety and efficacy not proven in childrenSafety and efficacy not proven in children
TellzyTellzy SAFETY PROFILESAFETY PROFILE
– Tolerability profile similar to placeboTolerability profile similar to placebo
– Mild and transient side effects- Mild and transient side effects-
headache,giddiness and fatigueheadache,giddiness and fatigue
– Better tolerated than ACE inhibitorsBetter tolerated than ACE inhibitors
lower incidence of coughlower incidence of cough
– Better tolerated than Amlodipine-Better tolerated than Amlodipine-
No Edema,flushing or reflex tachycardia.No Edema,flushing or reflex tachycardia.
TellzyTellzyDRUG INTERACTIONSDRUG INTERACTIONS
Not metabolized by cytochrome PNot metabolized by cytochrome P450 450 enzymes - Very low enzymes - Very low
potential for drug interactionspotential for drug interactions
Telmisartan does not alter kinetics of:Telmisartan does not alter kinetics of:
– AmlodipineAmlodipine
– GlibenclamideGlibenclamide
– WarfarinWarfarin
– HydrochlorothaizideHydrochlorothaizide
– SimvastatinSimvastatin
May increase serum digoxin levelsMay increase serum digoxin levels
TellzyTellzyPRECAUTIONSPRECAUTIONS
Similar to other ATSimilar to other AT11 blockers & ACE inhibitors: blockers & ACE inhibitors:
Use with caution in patients with-Use with caution in patients with-
Liver dysfunctionLiver dysfunction
Dehydration (Hypovolemia)Dehydration (Hypovolemia)
TellzyTellzy
CONTRA-INDICATIONSCONTRA-INDICATIONS
HypersensitivityHypersensitivity
PregnancyPregnancy
Bilateral renal artery stenosis- may lead to acute Bilateral renal artery stenosis- may lead to acute
renal failurerenal failure
Cardiovascular End Cardiovascular End Organ ProtectionOrgan Protection
MethodsMethods– Patients underwent double-blind randomizationPatients underwent double-blind randomization
8576 assigned to 10 mg of ramipril per day8576 assigned to 10 mg of ramipril per day 8542 assigned to 80 mg of telmisartan per day8542 assigned to 80 mg of telmisartan per day 8502 assigned to both drugs (combination therapy)8502 assigned to both drugs (combination therapy)
– Primary composite outcome –Primary composite outcome – death from cardiovascular causesdeath from cardiovascular causes myocardial infarctionmyocardial infarction StrokeStroke hospitalization for heart failure.hospitalization for heart failure.
ONTARGET ONTARGET TrialTrial
ONTARGETONTARGET
Blood Pressure Control:Blood Pressure Control:
Mean blood pressure was lower in both the Mean blood pressure was lower in both the
telmisartan group (a 0.9/0.6 mm Hg greater telmisartan group (a 0.9/0.6 mm Hg greater
reduction) and the combination-therapy group (a reduction) and the combination-therapy group (a
2.4/1.4 mm Hg greater reduction) than in the ramipril 2.4/1.4 mm Hg greater reduction) than in the ramipril
group. group.
N Engl J Med 2008;358:1547-59
ONTARGETONTARGET
1.1%
4.2%
0.1% 0.3%
0
1
2
3
4
5
% o
f P
atie
nt s
uffe
ring
from
adv
erse
eff
ect
Cough Angioedema
Telmisartan Good Safety Profile :Incidence of Cough & Angioedema is Low
Telmisartan
Ramipril
As compared with the ramipril group,the telmisartan group had lower rates of cough (1.1% vs. 4.2%, P<0.001) and angioedema(0.1% vs. 0.3%, P = 0.01)
N Engl J Med 2008;358:1547-59
ONTARGETONTARGET
Conclusion:Conclusion:
Telmisartan was equivalent to ramipril in patients Telmisartan was equivalent to ramipril in patients with vascular disease or highrisk diabetes and with vascular disease or highrisk diabetes and was associated was associated with less angioedema. with less angioedema.
N Engl J Med 2008;358:1547-59
The Telmisartan Randomised Assessment The Telmisartan Randomised Assessment Study in ACE iNtolerant subjects with Study in ACE iNtolerant subjects with
cardiovascular Disease (TRANSCEND) 1cardiovascular Disease (TRANSCEND) 1
BackgroundBackground ACE inhibitors reduce major cardiovascular ACE inhibitors reduce major cardiovascular
events but intolerant in 20% patientsevents but intolerant in 20% patients
Study assessed Telmisartan effectiveness Study assessed Telmisartan effectiveness in patients intolerant to ACE inhibitors with in patients intolerant to ACE inhibitors with cardiovascular disease or diabetes with cardiovascular disease or diabetes with end-organ damage end-organ damage
Lancet 2008; 372: 1174-1183
The Telmisartan Randomised Assessment The Telmisartan Randomised Assessment Study in ACE intolerant subjects with Study in ACE intolerant subjects with
cardiovascular Disease (TRANSCEND) 1cardiovascular Disease (TRANSCEND) 1
Evaluation of patients:Evaluation of patients:
The primary outcome was the composite of The primary outcome was the composite of
cardiovascular death, myocardial infarction, cardiovascular death, myocardial infarction,
stroke, or hospitalisation for heart failure. stroke, or hospitalisation for heart failure.
Lancet 2008; 372: 1174-1183
The Telmisartan Randomised Assessment The Telmisartan Randomised Assessment Study in ACE intolerant subjects with Study in ACE intolerant subjects with
cardiovascular Disease (TRANSCEND) 1cardiovascular Disease (TRANSCEND) 1
Patients: 5926 patients intolerant to ACE Patients: 5926 patients intolerant to ACE inhibitors were enrolled if they had inhibitors were enrolled if they had – Established coronary arteryEstablished coronary artery– Peripheral vascular or cerebrovascular diseasePeripheral vascular or cerebrovascular disease– Diabetes with end-organ damage. Diabetes with end-organ damage.
Treatment: Telmisartan 80 mg/day or placebo Treatment: Telmisartan 80 mg/day or placebo
Duration: 56 months. Duration: 56 months. Lancet 2008; 372: 1174-1183
ResultsResults
Mean blood pressure in Mean blood pressure in Telmisartan group lowerTelmisartan group lower than placebo through out the study period than placebo through out the study period
Primary Outcome:Primary Outcome:Fewer patients in the telmisartan Fewer patients in the telmisartan group experienced the primary composite outcomegroup experienced the primary composite outcome of cardiovascular death,myocardial infarction, stroke, of cardiovascular death,myocardial infarction, stroke, or hospitalisation for heart failure than did patients in or hospitalisation for heart failure than did patients in the placebo group( 15.7% vs 17% ) the placebo group( 15.7% vs 17% )
The Telmisartan Randomised Assessment The Telmisartan Randomised Assessment Study in ACE intolerant subjects with Study in ACE intolerant subjects with cardiovascular Disease (TRANSCEND)cardiovascular Disease (TRANSCEND)
Lancet 2008; 372: 1174-1183
The Telmisartan Randomised Assessment The Telmisartan Randomised Assessment Study in ACE intolerant subjects with Study in ACE intolerant subjects with cardiovascular Disease (TRANSCEND)cardiovascular Disease (TRANSCEND)
Hospitalized cardiovascular reason: Fewer patients Hospitalized cardiovascular reason: Fewer patients were hospitalised for cardiovascular reasons in the were hospitalised for cardiovascular reasons in the telmisartan group than in the placebo group ( 30.3% telmisartan group than in the placebo group ( 30.3% vs 33%, p =0.025)vs 33%, p =0.025)
Fewer permanent discontinuations in Telmisartan Fewer permanent discontinuations in Telmisartan group than in placebo group (21·6%group than in placebo group (21·6%vsvs 23·8% 23·8% p=0·055)p=0·055)
Lancet 2008; 372: 1174-1183
ConclusionConclusion– Telmisartan well tolerated in patients unable to Telmisartan well tolerated in patients unable to
tolerate ACE inhibitorstolerate ACE inhibitors
– Modestly reduced risk of composite outcome of Modestly reduced risk of composite outcome of cardiovascular death, myocardial infarction, or cardiovascular death, myocardial infarction, or strokestroke
The Telmisartan Randomised The Telmisartan Randomised Assessment Study in ACE intolerant Assessment Study in ACE intolerant subjects with cardiovascular Disease subjects with cardiovascular Disease
(TRANSCEND)(TRANSCEND)
1 Lancet 2008; 372: 1174-1183
TELMISARTAN TELMISARTAN VS. VS.
OTHER ANTI-HYPERTENSIVESOTHER ANTI-HYPERTENSIVES
Comparative Clinical Comparative Clinical TrialsTrials
Comparison with other ARBsComparison with other ARBs
Versus Losartan :Telmisartan monotherapy (40 or Versus Losartan :Telmisartan monotherapy (40 or 80mg OD) demonstrated superior anti-hypertensive 80mg OD) demonstrated superior anti-hypertensive efficacy to Losartan monotherapy (50mg or 100mg efficacy to Losartan monotherapy (50mg or 100mg OD)OD)
Versus Valsartan:Telmisartan monotherapy (40–Versus Valsartan:Telmisartan monotherapy (40–80mg OD) demonstrated better anti-hypertensive 80mg OD) demonstrated better anti-hypertensive efficacy than Valsartan monotherapy (80–160mg efficacy than Valsartan monotherapy (80–160mg once daily)once daily)
Drugs 2006;66(1) 51-83
ABPM comparison of telmisartan & ABPM comparison of telmisartan & losartan in mild to moderate losartan in mild to moderate
hypertensiveshypertensives
Aim: Anti-hypertensive efficacy & tolerability of Aim: Anti-hypertensive efficacy & tolerability of Telmisartan and Losartan compared with placebo Telmisartan and Losartan compared with placebo in a in a
6-week study6-week study
Patients: 223 patients with mild-to moderate Patients: 223 patients with mild-to moderate HypertensionHypertension
Treatment: Telmisartan 40 mg, telmisartan 80 Treatment: Telmisartan 40 mg, telmisartan 80 mg, losartan 50 mg, or placebomg, losartan 50 mg, or placebo
J Hum Hypertens. 1999 Oct;13(10):657-64.
Results: Results: – Ambulatory blood pressure monitoring (ABPM) after 6 Ambulatory blood pressure monitoring (ABPM) after 6
weeks showed all active treatments produced weeks showed all active treatments produced significant (P < 0.01) reductions from baseline in 24-significant (P < 0.01) reductions from baseline in 24-h mean SBP and DBP compared with placeboh mean SBP and DBP compared with placebo
– Reductions in SBP/DBP with Telmisartan 40 mg Reductions in SBP/DBP with Telmisartan 40 mg (10.7/6.8 mm Hg) and 80 mg (12.2/7. 1 mm Hg) were (10.7/6.8 mm Hg) and 80 mg (12.2/7. 1 mm Hg) were each significantly (P <0.05) greater than those each significantly (P <0.05) greater than those observed for Losartan 50 mg (6.0/3.7 mm Hg)observed for Losartan 50 mg (6.0/3.7 mm Hg)
– 24-h mean blood pressure control: Telmisartan 40 24-h mean blood pressure control: Telmisartan 40 mg and 80 mg were significantly (P< 0.05) better mg and 80 mg were significantly (P< 0.05) better than Losartan 50 mgthan Losartan 50 mg
J Hum Hypertens. 1999 Oct;13(10):657-64.
ABPM comparison of telmisartan & ABPM comparison of telmisartan & losartan in mild to moderate losartan in mild to moderate
hypertensiveshypertensives
-10.7/6.8mm Hg
-12.2/7.1 mm Hg
-6/3.7 mm Hg
-14
-12
-10
-8
-6
-4
-2
0
Re
du
ctio
n in
Blo
od
Pre
ssu
re
Telmisartan more effective anti-hypertensive during 18-24 hour peroid after dosing( P<0.05)
Telmisartan 40mg
Telmisartan 80mg
Losartan 50mg
J Hum Hypertens. 1999 Oct;13(10):657-64
ABPM comparison of telmisartan & ABPM comparison of telmisartan & losartan in mild to moderate losartan in mild to moderate
hypertensiveshypertensives
ABPM comparison of telmisartan & ABPM comparison of telmisartan & losartan in mild to moderate losartan in mild to moderate
hypertensiveshypertensives
Conclusion: Conclusion: – Telmisartan 40 mg and 80 mg once Telmisartan 40 mg and 80 mg once
daily were effective and well tolerated in daily were effective and well tolerated in the treatment of mild-to-moderate the treatment of mild-to-moderate hypertension, producing sustained 24-h hypertension, producing sustained 24-h blood pressure control which compared blood pressure control which compared favorably with Losartan.favorably with Losartan.
Comparison of Telmisartan vs. Valsartan Comparison of Telmisartan vs. Valsartan in mild to moderate hypertension usingin mild to moderate hypertension usingambulatory blood pressure monitoringambulatory blood pressure monitoring
AIM: Efficacy for 24-hour control of blood pressure AIM: Efficacy for 24-hour control of blood pressure assessed using ambulatory blood pressure assessed using ambulatory blood pressure monitoring monitoring
Results : Mean changes in diastolic blood pressure Results : Mean changes in diastolic blood pressure for the last 6 hours before dosing and the nighttime for the last 6 hours before dosing and the nighttime period were significantly greater with Telmisartan period were significantly greater with Telmisartan than with Valsartan (p<0.01 for the last 6 hours than with Valsartan (p<0.01 for the last 6 hours before dosing; p<0.05 for the nighttime period)before dosing; p<0.05 for the nighttime period)
J Clin Hypertens (Greenwich). 2002 Jul-Aug;4(4 Suppl 1):26-3
Comparison of Telmisartan vs. Valsartan Comparison of Telmisartan vs. Valsartan in mild to moderate hypertension usingin mild to moderate hypertension usingambulatory blood pressure monitoringambulatory blood pressure monitoring
Results :Results : Mean changes in systolic and diastolic blood Mean changes in systolic and diastolic blood
pressures for the 24-hour interval, the morning, and pressures for the 24-hour interval, the morning, and the daytime periods were significantly greater with the daytime periods were significantly greater with Telmisartan than with Valsartan (p<0.01)Telmisartan than with Valsartan (p<0.01)
The incidence of all adverse events and the most The incidence of all adverse events and the most common adverse events were comparable for common adverse events were comparable for patients receiving Telmisartan and patients patients receiving Telmisartan and patients receiving Valsartanreceiving Valsartan
Neither treatment was associated with coughNeither treatment was associated with coughJ Clin Hypertens (Greenwich). 2002 Jul-Aug;4(4 Suppl 1):26-31
Conclusion: Conclusion:
– Greater efficacy for Telmisartan than Valsartan Greater efficacy for Telmisartan than Valsartan in controlling blood pressure throughout the in controlling blood pressure throughout the 24-hour dosing interval,including the last 6 24-hour dosing interval,including the last 6 hours before dosinghours before dosing
– Two agents had similarly tolerabilityTwo agents had similarly tolerability
J Clin Hypertens (Greenwich). 2002 Jul-Aug;4(4 Suppl 1):26-31.
Comparison of Telmisartan vs. Valsartan Comparison of Telmisartan vs. Valsartan in mild to moderate hypertension usingin mild to moderate hypertension usingambulatory blood pressure monitoringambulatory blood pressure monitoring
ParametersParameters TelmisartanTelmisartan OlmesartanOlmesartan
24 hr control of BP*24 hr control of BP* Complete 24 hr control of Complete 24 hr control of BP BP Covers early morning hourCovers early morning hour
Incomplete 24 hr control Incomplete 24 hr control of BPof BP
Trough Peak RatioTrough Peak Ratio 66 -100 %66 -100 % 60 -80%60 -80%
PPAR – γ Agonistic PPAR – γ Agonistic activityactivity
Present therefore Improves Present therefore Improves insulin sensitivity and lipid insulin sensitivity and lipid profileprofile
AbsentAbsent
LipophilicityLipophilicity More Lipophilic so better More Lipophilic so better tissue penetration and hence tissue penetration and hence better inhibition of tissue better inhibition of tissue RAAS RAAS
Less lipophilic so less Less lipophilic so less inhibition of tissue inhibition of tissue RAAS.RAAS.
Renal Insufficiency Renal Insufficiency No dosage adjustmentNo dosage adjustment 20 mg maximum in 20 mg maximum in severe diseasesevere disease
Telmisartan vs. OlmesartanTelmisartan vs. Olmesartan
Telmisartan vs. LosartanTelmisartan vs. LosartanParametersParameters TelmisartanTelmisartan LosartanLosartan
24 hr control of BP covers early 24 hr control of BP covers early morning hourmorning hour
Complete 24 hr control of BP Complete 24 hr control of BP Cover early morning hourCover early morning hour
Incomplete 24 hr control of Incomplete 24 hr control of BPBPMay not cover early morning May not cover early morning hourhour
Trough Peak RatioTrough Peak Ratio 66 -100 %66 -100 % 65%65%
PPAR – γ Agonistic activityPPAR – γ Agonistic activity Present therefore Improves Present therefore Improves insulin sensitivity and lipid insulin sensitivity and lipid profileprofile
AbsentAbsent
LipophilicityLipophilicity More Lipophilic so better More Lipophilic so better tissue penetration and hence tissue penetration and hence better inhibition of tissue better inhibition of tissue RAAS RAAS
Less lipophilic so less Less lipophilic so less inhibition of tissue RAAS.inhibition of tissue RAAS.
Drug InteractionsDrug Interactions LessLess MoreMore
IndicationsIndications HypertensionHypertension Hypertension, Diabetic Hypertension, Diabetic nephropathy in type 2 nephropathy in type 2 diabetes mellitus with diabetes mellitus with hypertension, stroke hypertension, stroke reduction with hypertension reduction with hypertension and left ventricular and left ventricular hypertrophy hypertrophy
Comparison vs ACE InhibitorsComparison vs ACE Inhibitors
Telmisartan has better tolerability profile as Telmisartan has better tolerability profile as compared to ACE inhibitorscompared to ACE inhibitors
Due to better Tolerability profile the patient Due to better Tolerability profile the patient compliance is bettercompliance is better
Therefore, Telmisartan may provide better long Therefore, Telmisartan may provide better long term blood pressure control than ACE inhibitors.term blood pressure control than ACE inhibitors.
J Int Med Res. 2002 Nov-Dec;30(6):543-52.
ABPM comparison of Telmisartan and ABPM comparison of Telmisartan and Enalapril in patients with mild-to-moderate Enalapril in patients with mild-to-moderate
hypertension (PROBE study)hypertension (PROBE study)
Patients: 522 patients with mild-to moderate Patients: 522 patients with mild-to moderate hypertensionhypertension
Treatment: Telmisartan 40/ 80 mg vs Enalapril Treatment: Telmisartan 40/ 80 mg vs Enalapril 10-20 mg once-daily 10-20 mg once-daily
Duration: Twelve week study in which Duration: Twelve week study in which ambulatory blood pressure monitoring (ABPM)ambulatory blood pressure monitoring (ABPM)
ABPM comparison of Telmisartan and ABPM comparison of Telmisartan and Enalapril in patients with mild-to-Enalapril in patients with mild-to-
moderate hypertension (PROBE study)moderate hypertension (PROBE study) Significantly greater proportion of patients achieved Significantly greater proportion of patients achieved
seated diastolic response with telmisartan than enalapril seated diastolic response with telmisartan than enalapril (59% versus 50%; P < 0.05)(59% versus 50%; P < 0.05)
J Int Med Res. 2002 Nov-Dec;30(6):543-52.
59%
50%
44
46
48
50
52
54
56
58
60
% o
f P
atient show
ing D
iasto
lic
response
Telmisartan more effective in achieving Patient response in controlling Diastolic Blood Pressure(p<0.05)
Telmisartan
Enalapril
Results:Results:
Tolerability Profile:Compared with telmisartan, Tolerability Profile:Compared with telmisartan, enalapril was associated with a enalapril was associated with a higher incidence of higher incidence of coughcough (8.9% versus 0.8%) and (8.9% versus 0.8%) and hypotensionhypotension (3.9% (3.9% versus 1.1%)versus 1.1%)
Conclusion: Conclusion:
Telmisartan may provide better long-term Telmisartan may provide better long-term compliance and consequently, better blood compliance and consequently, better blood pressure control than enalaprilpressure control than enalapril
J Int Med Res. 2002 Nov-Dec;30(6):543-52.
ABPM comparison of Telmisartan and ABPM comparison of Telmisartan and Enalapril in patients with mild-to-moderate Enalapril in patients with mild-to-moderate
hypertension (PROBE study)hypertension (PROBE study)
Telmisartan vs. ACE inhibitorsTelmisartan vs. ACE inhibitors
Telmisartan produces more complete inhibition of Telmisartan produces more complete inhibition of
the RAASthe RAAS
Telmisartan therapy does not produce the side Telmisartan therapy does not produce the side
effect of dry cough ( 20-30% of patients develop effect of dry cough ( 20-30% of patients develop
dry cough with ACE inhibitors)dry cough with ACE inhibitors)
Telmisartan therapy provides better 24-hr control Telmisartan therapy provides better 24-hr control
of blood pressure than Enalaprilof blood pressure than Enalapril
Telmisartan is better tolerated than ACE inhibitorsTelmisartan is better tolerated than ACE inhibitors
Improved patient complianceImproved patient compliance
Versus Calcium Channel Blockers:Versus Calcium Channel Blockers:Comparison of efficacies & duration of Comparison of efficacies & duration of action of Telmisartan and Amlodipineaction of Telmisartan and Amlodipine
Patients: 234 patients with hypertensionPatients: 234 patients with hypertensionTreatment:Treatment:
40 mg Telmisartan increased to 80 and 120 mg as 40 mg Telmisartan increased to 80 and 120 mg as necessary for patients necessary for patients
5 mg Amlodipine titrated to 10 mg as necessary 5 mg Amlodipine titrated to 10 mg as necessary for patients for patients
Placebo (n = 81)Placebo (n = 81) 12 weeks of double-blind treatment12 weeks of double-blind treatment
Both drugs also significantly reduced 24 h mean Both drugs also significantly reduced 24 h mean systolic blood pressures and DBP compared with systolic blood pressures and DBP compared with placebo (P < 0.0001)placebo (P < 0.0001)
Blood Press Monit. 1998 Oct;3(5):295-302.
71%
55%
0
10
20
30
40
50
60
70
80
% p
atie
nts
with
Tw
enty
four
-hou
r m
ean
AB
PM
DB
P <
85
mm
Hg
Telmisartan effective in controlling Diastolic Blood pressure
Telmisartan
Amlodipine
Blood Press Monit. 1998 Oct;3(5):295-302.
Comparison of efficacies & duration of Comparison of efficacies & duration of action of Telmisartan and Amlodipineaction of Telmisartan and Amlodipine
Twenty four-hour mean ABPM DBP < 85 mmHg were observed in 71% of telmisartan patients and in 55% of patients administered amlodipine
Reductions in DBP with telmisartan greater (P < Reductions in DBP with telmisartan greater (P < 0.05) than with amlodipine during the night-time 0.05) than with amlodipine during the night-time interval and the last 4 h of the dosing periodinterval and the last 4 h of the dosing period
Both telmisartan and amlodipine well toleratedBoth telmisartan and amlodipine well tolerated– Drug-related edema occurred significantly more Drug-related edema occurred significantly more
commonly (P < 0.05) among the patients commonly (P < 0.05) among the patients administered amlodipine than it did among administered amlodipine than it did among patients administered either telmisartan or patients administered either telmisartan or placeboplacebo
Blood Press Monit. 1998 Oct;3(5):295-302.
Comparison of efficacies & duration of Comparison of efficacies & duration of action of Telmisartan and Amlodipineaction of Telmisartan and Amlodipine
Telmisartan vs. AmlodipineTelmisartan vs. Amlodipine
Telmisartan provides better control of blood pressure Telmisartan provides better control of blood pressure
than Amlodipine during the pre-dose interval ( 4-6 hrs than Amlodipine during the pre-dose interval ( 4-6 hrs
before the next morning dose)before the next morning dose)
Telmisartan is better tolerated than Amlodipine: Side Telmisartan is better tolerated than Amlodipine: Side
effect of pedal edema is seen frequently with effect of pedal edema is seen frequently with
AmlodipineAmlodipine
Telmisartan is preferred over Amlodipine in Telmisartan is preferred over Amlodipine in
hypertensive patients with diabetic nephropathy hypertensive patients with diabetic nephropathy
(proteinuria) & in patients with heart failure(proteinuria) & in patients with heart failure
Comparison of 26-week efficacy and Comparison of 26-week efficacy and tolerability of Telmisartan and Atenololtolerability of Telmisartan and Atenolol
Patients:Patients: 533 patients with mild- moderate 533 patients with mild- moderate hypertension hypertension
Duration:Duration: 26-week 26-week
Treatment :Treatment : - Telmisartan (40 mg titrated to 80 mg titrated - Telmisartan (40 mg titrated to 80 mg titrated to 120 mg) to 120 mg) - Atenolol (50 mg titrated to 100 mg) - Atenolol (50 mg titrated to 100 mg) - Hydrochlorothiazide (HCTZ) 12.5 or 25 mg was - Hydrochlorothiazide (HCTZ) 12.5 or 25 mg was added if neededadded if needed
Clin Ther. 2001 Jan;23(1):108-23.
80%
68%
60
65
70
75
80
% o
f Pat
ient
sho
wing
Re
duct
ion
of S
BP >
or
= 10
mm
Hg
Telmisartan more effective than Atenolol in Controlling Systolic Blood Pressure(p=0.003)
Telmisartan
Atenolol
Clin Ther. 2001 Jan;23(1):108-23.
Comparison of 26-week efficacy and Comparison of 26-week efficacy and tolerability of Telmisartan and Atenololtolerability of Telmisartan and Atenolol
Reduction from baseline in SBP of > or = 10 mm Hg achieved by 80% of Telmisartan-treated and 68% of Atenolol-treated patients (P = 0.003)
Comparison of 26-week efficacy and Comparison of 26-week efficacy and tolerability of Telmisartan and Atenololtolerability of Telmisartan and Atenolol
ResultResult
Final SBP/DBP reductions of 20.9/14.4 mm Hg for Final SBP/DBP reductions of 20.9/14.4 mm Hg for Telmisartan versus 16.7/13.3 mm Hg for AtenololTelmisartan versus 16.7/13.3 mm Hg for Atenolol
Difference in SBP was significant (P = 0.005)Difference in SBP was significant (P = 0.005)
Clin Ther. 2001 Jan;23(1):108-23.
Comparison of 26-week efficacy and Comparison of 26-week efficacy and tolerability of Telmisartan and Atenololtolerability of Telmisartan and Atenolol
Safety Profile:Safety Profile: Mild to moderate adverse events reported by 52.7% Mild to moderate adverse events reported by 52.7%
of patients given Telmisartan and 61.2% of patients of patients given Telmisartan and 61.2% of patients given Atenolol difference not statistically significantgiven Atenolol difference not statistically significant
Fatigue and male impotence more common in Fatigue and male impotence more common in atenolol-treated patients (3.4% and 4.0% resp)atenolol-treated patients (3.4% and 4.0% resp)
Conclusions: Conclusions: Telmisartan appears to be at least as effective as Telmisartan appears to be at least as effective as
Atenolol in the treatment of mild to moderate Atenolol in the treatment of mild to moderate hypertension and may be better tolerated. hypertension and may be better tolerated.
Clin Ther. 2001 Jan;23(1):108-23.
Telmisartan vs. AtenololTelmisartan vs. Atenolol
No adverse effect on lipid or carbohydrate metabolismNo adverse effect on lipid or carbohydrate metabolism
Safe in Bronchial asthma, heart block, bradycardiaSafe in Bronchial asthma, heart block, bradycardia
Better tolerated- No rebound hypertension, cold Better tolerated- No rebound hypertension, cold
extremities, fatigue, impotenceextremities, fatigue, impotence
Telmisartan in isolated systolic Telmisartan in isolated systolic hypertension (ARAMIS) Studyhypertension (ARAMIS) Study
Aim: Efficacy and safety of Telmisartan 20, 40 or Aim: Efficacy and safety of Telmisartan 20, 40 or 80 mg versus hydrochlorothiazide 12.5 mg or 80 mg versus hydrochlorothiazide 12.5 mg or placeboplacebo
Patients:1039 patients (age 36-84 years) with Patients:1039 patients (age 36-84 years) with isolated systolic hypertension (ISH) [seated SBP isolated systolic hypertension (ISH) [seated SBP 150-179 mmHg and seated diastolic blood 150-179 mmHg and seated diastolic blood pressure (DBP) < 90 mmHg] pressure (DBP) < 90 mmHg]
J Hypertens. 2004 May;22(5):1033-7.
Telmisartan in isolated systolic Telmisartan in isolated systolic hypertension (ARAMIS) Studyhypertension (ARAMIS) Study
Treatment :Once-daily treatment with Telmisartan 20, Treatment :Once-daily treatment with Telmisartan 20, 40 or 80 mg, hydrochlorothiazide 12.5 mg, or placebo40 or 80 mg, hydrochlorothiazide 12.5 mg, or placebo
Conclusion: Conclusion: – All doses of Telmisartan (20-80 mg) significantly All doses of Telmisartan (20-80 mg) significantly
superior to placebo in reducing SBP in patients with superior to placebo in reducing SBP in patients with ISH and clinically comparable to HCTZ 12.5 mgISH and clinically comparable to HCTZ 12.5 mg
– Tolerability of Telmisartan similar to placeboTolerability of Telmisartan similar to placebo
J Hypertens. 2004 May;22(5):1033-7.
In Combination with Other In Combination with Other Antihypertensive AgentsAntihypertensive Agents
Adjunctive therapy with Telmisartan Adjunctive therapy with Telmisartan calcium channel antagonistcalcium channel antagonist a β-blockera β-blocker a diuretic agenta diuretic agent
Was effective in controlling Blood PressureWas effective in controlling Blood Pressure
Drugs 2006; 66 (1)
Salient FeaturesSalient Features Once daily dose of Telmisartan provides better 24-hr Once daily dose of Telmisartan provides better 24-hr
control of blood pressure, even in the crucial early morning control of blood pressure, even in the crucial early morning
hours hours
Telmisartan provides better 24 hr control of blood pressure Telmisartan provides better 24 hr control of blood pressure
than Enalapril, Amlodipine, Losartan & Valsartanthan Enalapril, Amlodipine, Losartan & Valsartan
Adverse event rates are significantly lower than with other Adverse event rates are significantly lower than with other
classes of antihypertensive drugs including ACE inhibitorsclasses of antihypertensive drugs including ACE inhibitors
No dosage adjustment is required in renal insufficiency No dosage adjustment is required in renal insufficiency
patientspatients
Salient FeaturesSalient Features Telmisartan has very low potential for drug interactions Telmisartan has very low potential for drug interactions
Telmisartan displays favorable effects on Left ventricular Telmisartan displays favorable effects on Left ventricular hypertrophy and renal functionhypertrophy and renal function
Telmisartan improves the insulin sensitivity and lipid profile.Telmisartan improves the insulin sensitivity and lipid profile.
Telmisartan is particularly useful in following groups of Telmisartan is particularly useful in following groups of hypertensive patients:hypertensive patients:– A. Intolerance to ACE inhibitorA. Intolerance to ACE inhibitor– B. DiabeticsB. Diabetics– C. Patients with heart failureC. Patients with heart failure– D. ElderlyD. Elderly– E. Renal impairmentE. Renal impairment
Improved patient compliance due to once daily dosage & Improved patient compliance due to once daily dosage & excellent tolerabilityexcellent tolerability
Indications: HypertensionIndications: Hypertension Telmisartan is recommended for the treatment of Telmisartan is recommended for the treatment of
hypertension in adults, either as monotherapy or in hypertension in adults, either as monotherapy or in combination with other antihypertensive agentscombination with other antihypertensive agents
The dosage regimen of Telmisartan should be The dosage regimen of Telmisartan should be individualized for the patient, with the usual starting individualized for the patient, with the usual starting dose being 40mg once daily.dose being 40mg once daily.
If additional BP lowering beyond that achieved with If additional BP lowering beyond that achieved with Telmisartan 80mg once daily is required, then the Telmisartan 80mg once daily is required, then the addition of another antihypertensive agent may be addition of another antihypertensive agent may be considered. considered.
Telmisartan may be administered without regard to foodTelmisartan may be administered without regard to food
Drugs 2006; 66 (1)
Temisartan FDA IndicationsTemisartan FDA Indications
HypertensionHypertension– Indicated for treatment of hypertensionIndicated for treatment of hypertension
– May be used alone or in combination with May be used alone or in combination with other antihypertensive agentsother antihypertensive agents
Temisartan FDA IndicationsTemisartan FDA Indications
Cardiovascular Risk ReductionCardiovascular Risk Reduction– Indicated for risk reduction of myocardial Indicated for risk reduction of myocardial
infarction, stroke, or death from cardiovascular infarction, stroke, or death from cardiovascular causes in patients 55 years of age or older at causes in patients 55 years of age or older at high risk of developing major cardiovascular high risk of developing major cardiovascular events events who are unable to take ACE inhibitors.who are unable to take ACE inhibitors.
– High risk for cardiovascular events can be High risk for cardiovascular events can be evidenced by a history of coronary artery evidenced by a history of coronary artery disease, peripheral arterial disease, stroke, disease, peripheral arterial disease, stroke, transient ischemic attack, or high-risk diabetes transient ischemic attack, or high-risk diabetes (insulin-dependent or non-insulin dependent) with (insulin-dependent or non-insulin dependent) with evidence of end-organ damageevidence of end-organ damage
– Use of telmisartan with an ACE inhibitor is not Use of telmisartan with an ACE inhibitor is not recommendedrecommended
Place of Telmisartan in thePlace of Telmisartan in theManagement of HypertensionManagement of Hypertension
European Society of Hypertension/European European Society of Hypertension/European Society of Cardiology guidelines recommend the Society of Cardiology guidelines recommend the use of agents that provide 24-hour efficacy with a use of agents that provide 24-hour efficacy with a once-daily dose.once-daily dose.
Long acting drugs may offer advantages to short-Long acting drugs may offer advantages to short-acting agents for a number of reasons, including acting agents for a number of reasons, including greater compliance, sustained BP control, greater compliance, sustained BP control, maintenance of control regardless of missing a maintenance of control regardless of missing a dose and a reduced risk of cardiovascular events dose and a reduced risk of cardiovascular events during the early morning hours.during the early morning hours.
Drugs 2006; 66 (1)
Place of Telmisartan in thePlace of Telmisartan in theManagement of HypertensionManagement of Hypertension
Telmisartan is an AII receptor antagonist with a Telmisartan is an AII receptor antagonist with a long duration of action and shows no evidence of long duration of action and shows no evidence of drug accumulation after repeated administrationdrug accumulation after repeated administration
A T A T 1/21/2 of approximately 24 hours for Telmisartan of approximately 24 hours for Telmisartan considerably longer than that observed with other considerably longer than that observed with other agents in this class (all ≤15 hours), ensures that agents in this class (all ≤15 hours), ensures that it will provide consistent and sustained reductions it will provide consistent and sustained reductions in BP over 24 hoursin BP over 24 hours
Drugs 2006; 66 (1)
Place of Telmisartan in Management Place of Telmisartan in Management of Hypertensionof Hypertension
Clinical trials and the clinical practice setting indicates Clinical trials and the clinical practice setting indicates that Telmisartan, either as monotherapy or in that Telmisartan, either as monotherapy or in combination with other antihypertensive agents, is combination with other antihypertensive agents, is effective in a broad spectrum of hypertensive patients:effective in a broad spectrum of hypertensive patients:
– Including the elderly Including the elderly – Those with coexisting type 2 diabetesThose with coexisting type 2 diabetes– Metabolic syndrome Metabolic syndrome – Renal impairment. Renal impairment.
Drugs 2006; 66 (1)
Place of Telmisartan in thePlace of Telmisartan in theManagement of HypertensionManagement of Hypertension
Consistent antihypertensive efficacy during the Consistent antihypertensive efficacy during the entire 24-hour dosage interval and sustained BP-entire 24-hour dosage interval and sustained BP-lowering effect in the long term combined with its lowering effect in the long term combined with its favorable tolerability profilefavorable tolerability profile
Telmisartan is a valuable first-line treatment Telmisartan is a valuable first-line treatment option for the management of essential option for the management of essential hypertensionhypertension
Drugs 2006; 66 (1)
Tellzy-HTellzy-H
COMPOSITION:COMPOSITION:
Telmisartan…………..…… 40 mgTelmisartan…………..…… 40 mg
Hydrochlorothiazide …….. 12.5 mgHydrochlorothiazide …….. 12.5 mg
Extra- Cardiac Extra- Cardiac EffectsEffects
INNOVATION StudyINNOVATION StudyIncipient to Overt: Incipient to Overt:
Angiotensin IIAngiotensin II
Blocker, Telmisartan, Blocker, Telmisartan, Investigation onInvestigation on
Type 2 Diabetic NephropathyType 2 Diabetic Nephropathy
DIABETES CARE, VOLUME 30, NUMBER 6, JUNE 2007
Prevention of Transition From Incipient Prevention of Transition From Incipient to Overt Nephropathy With Telmisartan to Overt Nephropathy With Telmisartan
in Patients With Type 2 Diabetesin Patients With Type 2 Diabetes
INNOVATION Study :INNOVATION Study :
First large-scale clinical study to investigate First large-scale clinical study to investigate
prevention of overt diabetic nephropathy using an prevention of overt diabetic nephropathy using an
ARB in normotensive and ARB in normotensive and hypertensive Japanese hypertensive Japanese
patients with type 2 diabetespatients with type 2 diabetes
Objective : Evaluate efficacy of Telmisartan in Objective : Evaluate efficacy of Telmisartan in
preventing transition from microalbuminuria to overt preventing transition from microalbuminuria to overt
nephropathy in Japanese patients nephropathy in Japanese patients
DIABETES CARE, VOLUME 30, NUMBER 6, JUNE 2007
Prevention of Transition From Prevention of Transition From Incipient to Overt Nephropathy With Incipient to Overt Nephropathy With Telmisartan in Patients With Type 2 Telmisartan in Patients With Type 2
DiabetesDiabetesPatients: Patients: A total of 527 type 2 diabetes patients and A total of 527 type 2 diabetes patients and
urinary albumin-to-creatinine ratio (UACR) 100–urinary albumin-to-creatinine ratio (UACR) 100–
300mg/g and serum creatinine <1.5 mg/dl (men) and 300mg/g and serum creatinine <1.5 mg/dl (men) and
<1.3mg/dl (women) <1.3mg/dl (women)
Treatment :Treatment :
80 or 40 mg Telmisartan or placebo80 or 40 mg Telmisartan or placebo
The starting dose was 20 mg, titrated to 40 mg after 2 The starting dose was 20 mg, titrated to 40 mg after 2
weeks or to 80 mg after a further 2 weeksweeks or to 80 mg after a further 2 weeks
DIABETES CARE, VOLUME 30, NUMBER 6, JUNE 2007
INNOVATION StudyINNOVATION Study
Evaluation:Evaluation: Primary efficacy end point: transition rate from Primary efficacy end point: transition rate from
incipient to overt nephropathy (UACR >300 mg/g incipient to overt nephropathy (UACR >300 mg/g and increase ≥30% from baseline at two and increase ≥30% from baseline at two consecutive 4-week visits)consecutive 4-week visits)
Secondary end point: microalbuminuria remission Secondary end point: microalbuminuria remission (UACR < 30 mg/g)(UACR < 30 mg/g)
Mean duration of follow-up was 1.3 yearsMean duration of follow-up was 1.3 years
DIABETES CARE, VOLUME 30, NUMBER 6, JUNE 2007
INNOVATION StudyINNOVATION Study
16.7%22.6%
49.9%
0
10
20
30
40
50
% o
f In
cip
ien
t N
ep
hro
pa
thy
pa
tien
ts
con
vert
ed
to O
vert
Ne
ph
rop
ath
y
Telmisartan Prevents Transition from Incipient Nephropathy to Overt Nephropathy ( p <0.0001)
Telmisartan 80mg
Telmisartan 40mg
Placebo
Diabetes care, Volume 30, Number 6, June 2007
Transition rates to overt nephropathy: Telmisartan 80mg (n = 168) 16.7%, Telmisartan 40 mg (n= 172) 22.6%, and placebo (n . 174) 49.9% (both Telmisartan doses vs. placebo, P < 0.0001)
INNOVATION StudyINNOVATION Study
21.2%
12.8%
1.2%
0
5
10
15
20
25
% P
atie
nts
with
M
icro
alb
um
inu
ria
re
mm
isio
n
Telmisartan effective in Promoting Microalbuminuria remmision (p< 0.001)
Telmisartan 80mg
Telmisartan 40mg
Placebo
DIABETES CARE, VOLUME 30, NUMBER 6, JUNE 2007
INNOVATION StudyINNOVATION Study
Conclusion: Conclusion:
Patients with type 2 diabetes and microalbuminuria Patients with type 2 diabetes and microalbuminuria receiving 80 or 40 mg telmisartanreceiving 80 or 40 mg telmisartan– Superior renoprotection, demonstrated by lower Superior renoprotection, demonstrated by lower
transition rates to overt nephropathy, compared with transition rates to overt nephropathy, compared with placeboplacebo
Achievement of microalbuminuria remission was Achievement of microalbuminuria remission was superior with 80 or 40 mg telmisartan than with placebosuperior with 80 or 40 mg telmisartan than with placebo
Telmisartan reduced transition from incipient to overt Telmisartan reduced transition from incipient to overt nephropathy and induced remission of albuminuria in nephropathy and induced remission of albuminuria in Japanese type 2 diabetic patientsJapanese type 2 diabetic patients
DIABETES CARE, VOLUME 30, NUMBER 6, JUNE 2007
Effects on Glucose Effects on Glucose MetabolismMetabolism
Effects on glucose metabolismEffects on glucose metabolism
Overactivity of the renin–angiotensin system is Overactivity of the renin–angiotensin system is likely to impair insulin signaling and contribute to likely to impair insulin signaling and contribute to insulin resistanceinsulin resistance
Inhibition of the renin–angiotensin system by Inhibition of the renin–angiotensin system by ARBs might be expected to reduce insulin ARBs might be expected to reduce insulin resistance, thereby improving glucose resistance, thereby improving glucose metabolism and metabolic syndrome metabolism and metabolic syndrome
Expert Opin. Pharmacother. (2008) 9(8):1397-1406
Effects on glucose metabolismEffects on glucose metabolism
Effect on Glucose metabolism is proposed to be Effect on Glucose metabolism is proposed to be mediated through mediated through PPAR- γ activityPPAR- γ activity
Among ARBs, Telmisartan has the strongest Among ARBs, Telmisartan has the strongest ability to activate PPAR- γ in vitroability to activate PPAR- γ in vitro
PPAR- γ activation by Telmisartan occurs at PPAR- γ activation by Telmisartan occurs at clinically relevant concentrations of the drug clinically relevant concentrations of the drug
Expert Opin. Pharmacother. (2008) 9(8):1397-1406
Metabolic effect of Telmisartan and Metabolic effect of Telmisartan and Losartan in hypertensiveLosartan in hypertensive
patients with metabolic syndromepatients with metabolic syndrome Background: Metabolic syndrome is a cluster of Background: Metabolic syndrome is a cluster of
common cardiovascular risk factors that includes common cardiovascular risk factors that includes hypertension, hypertriglyceredemia and insulin hypertension, hypertriglyceredemia and insulin resistance resistance
Hypertension and diabetes mellitus are frequent co-Hypertension and diabetes mellitus are frequent co-morbidities and, like metabolic syndrome, increase the morbidities and, like metabolic syndrome, increase the risk of cardiovascular events risk of cardiovascular events
Telmisartan, an antihypertensive agent with evidence of Telmisartan, an antihypertensive agent with evidence of partial peroxisome proliferator-activated receptor partial peroxisome proliferator-activated receptor activity gamma (PPAR γ) activity, may improve insulin activity gamma (PPAR γ) activity, may improve insulin sensitivity and lipid profile in patients with metabolic sensitivity and lipid profile in patients with metabolic syndromesyndrome
Cardiovascular Diabetology 2005, 4:6
Metabolic effect of Telmisartan and Metabolic effect of Telmisartan and Losartan in hypertensiveLosartan in hypertensive
patients with metabolic syndromepatients with metabolic syndrome
Methods: Methods: – 40 patients with metabolic syndrome received 40 patients with metabolic syndrome received
once-daily doses of Telmisartan 80 mg or once-daily doses of Telmisartan 80 mg or Losartan 50 mg for 3 months Losartan 50 mg for 3 months
– At baseline and end of treatment, fasting and At baseline and end of treatment, fasting and postprandial plasma glucose, insulin postprandial plasma glucose, insulin sensitivity, glycosylated haemoglobin (HBA 1c ) sensitivity, glycosylated haemoglobin (HBA 1c ) and 24-hour mean systolic and diastolic blood and 24-hour mean systolic and diastolic blood pressures were determinedpressures were determined
Cardiovascular Diabetology 2005, 4:6
Metabolic effect of Telmisartan and Metabolic effect of Telmisartan and Losartan in hypertensiveLosartan in hypertensive
patients with metabolic syndromepatients with metabolic syndromeResults: Results:
Telmisartan, but not losartan, significantly (p < Telmisartan, but not losartan, significantly (p < 0.05) reduced free plasma glucose, free plasma 0.05) reduced free plasma glucose, free plasma insulin, homeostasis model assessment of insulin insulin, homeostasis model assessment of insulin resistance and HbA resistance and HbA ICIC
Plasma glucose and insulin were reduced during Plasma glucose and insulin were reduced during the oral glucose tolerance test by Telmisartan, but the oral glucose tolerance test by Telmisartan, but not by losartan not by losartan
Telmisartan also significantly reduced 24-hour Telmisartan also significantly reduced 24-hour mean systolic blood pressure (p < 0.05) and mean systolic blood pressure (p < 0.05) and diastolic blood pressure (p < 0.05) compared with diastolic blood pressure (p < 0.05) compared with losartanlosartan
Cardiovascular Diabetology 2005, 4:6
Cardiovascular Diabetology 2005, 4:6
Cardiovascular Diabetology 2005, 4:6
Cardiovascular Diabetology 2005, 4:6
Effect of Telmisartan and Losartan Effect of Telmisartan and Losartan during OGTT patients with metabolic during OGTT patients with metabolic
syndromesyndrome
Before treatment After treatment
Metabolic effect of Telmisartan and Metabolic effect of Telmisartan and Losartan in hypertensiveLosartan in hypertensive
patients with metabolic syndromepatients with metabolic syndrome
Conclusion: Conclusion:
In addition to providing superior 24-hour blood In addition to providing superior 24-hour blood
pressure control, Telmisartan, unlike Losartan, pressure control, Telmisartan, unlike Losartan,
displayed insulin-sensitizing activity, which may be displayed insulin-sensitizing activity, which may be
explained by its partial PPARγ activityexplained by its partial PPARγ activity
Cardiovascular Diabetology 2005, 4:6
Effects on Lipid Effects on Lipid MetabolismMetabolism
Effect of Telmisartan on Cholesterol Effect of Telmisartan on Cholesterol Levels in Patients with Hypertension - Levels in Patients with Hypertension -
Saga Telmisartan Aggressive Research Saga Telmisartan Aggressive Research (STAR)(STAR)
Patients :A total of 197 patients with a systolic blood Patients :A total of 197 patients with a systolic blood pressure of ≥140 or a diastolic blood pressure of pressure of ≥140 or a diastolic blood pressure of ≥90 mmHg were enrolled≥90 mmHg were enrolled
Treatment : Patients prescribed 20 to 80 mg/day of Treatment : Patients prescribed 20 to 80 mg/day of Telmisartan for 6 monthsTelmisartan for 6 months
Results: In all patients, both systolic and diastolic Results: In all patients, both systolic and diastolic blood pressures decreasedblood pressures decreased– Systolic : 159 to 135 mm Hg, p<0.0001 Systolic : 159 to 135 mm Hg, p<0.0001 – Diastolic: 87 to 75 mm Hg, p<0.0001Diastolic: 87 to 75 mm Hg, p<0.0001
Horm Metab Res 2007; 39(5): 372-376
Effect of Telmisartan on Cholesterol Effect of Telmisartan on Cholesterol Levels in Patients with Hypertension - Levels in Patients with Hypertension -
Saga Telmisartan Aggressive Research Saga Telmisartan Aggressive Research (STAR)(STAR)
Horm Metab Res 2007; 39(5): 372-376
EffectEffect of Telmisartan on Cholesterol of Telmisartan on Cholesterol Levels in Patients withLevels in Patients with
HypertensionHypertension - Saga Telmisartan - Saga Telmisartan Aggressive Research (STAR)Aggressive Research (STAR)
Effects of telmisartan on Effects of telmisartan on
total cholesterol reduction total cholesterol reduction
in patients with levels in patients with levels ≥ ≥ 220 mg/dl220 mg/dl
Horm Metab Res 2007; 39(5): 372-376
Effect of Telmisartan on Cholesterol Effect of Telmisartan on Cholesterol Levels in Patients withLevels in Patients with
Hypertension - Saga Telmisartan Hypertension - Saga Telmisartan Aggressive Research (STAR)Aggressive Research (STAR)
Patients receiving statins Patients receiving statins
Horm Metab Res 2007; 39(5): 372-376
Effect of Telmisartan on Cholesterol Effect of Telmisartan on Cholesterol Levels in Patients withLevels in Patients with
Hypertension - Saga Telmisartan Hypertension - Saga Telmisartan Aggressive Research (STAR)Aggressive Research (STAR)
In patients receiving In patients receiving telmisartan in exchange telmisartan in exchange for other ARBs with total for other ARBs with total cholesterol ≥ 220 mg/dl cholesterol ≥ 220 mg/dl
Horm Metab Res 2007; 39(5): 372-376
Effect of Telmisartan on Cholesterol Effect of Telmisartan on Cholesterol Levels in Patients withLevels in Patients with
Hypertension - Saga Telmisartan Hypertension - Saga Telmisartan Aggressive Research (STAR)Aggressive Research (STAR)
Fasting blood glucose (FBG) was decreased (158 to Fasting blood glucose (FBG) was decreased (158 to 138 mg/dl, p<0.05) in patients with FBG ≥110 mg/dl138 mg/dl, p<0.05) in patients with FBG ≥110 mg/dl
Conclusion:Conclusion:
Telmisartan may have favorable effects on lipid and Telmisartan may have favorable effects on lipid and glucose metabolism, in addition to lowering blood glucose metabolism, in addition to lowering blood pressurepressure
Profound effect of Telmisartan to lower cholesterol Profound effect of Telmisartan to lower cholesterol suggests a potential use in hypertensive patients suggests a potential use in hypertensive patients with dyslipidemiawith dyslipidemia
Horm Metab Res 2007; 39(5): 372-376
Telmisartan: Lipid Lowering MechanismTelmisartan: Lipid Lowering Mechanism
Hypertrigriceridaemia is often complicated in Hypertrigriceridaemia is often complicated in patients with Type 2 diabetes or insulin resistance. patients with Type 2 diabetes or insulin resistance.
PPARs – PPAR- α as well as PPAR- γ – play a role in PPARs – PPAR- α as well as PPAR- γ – play a role in intracellular lipid metabolism by upregulating the intracellular lipid metabolism by upregulating the expression of the enzyme involved in the expression of the enzyme involved in the conversion of fatty acid in acyl-CoA esters, fatty conversion of fatty acid in acyl-CoA esters, fatty acid entry into mitochondria, and peroxisomal and acid entry into mitochondria, and peroxisomal and mitochondrial fatty acid catabolismmitochondrial fatty acid catabolism
PPAR- γ activation of telmisartan may also PPAR- γ activation of telmisartan may also contribute to its hypotriglyceridaemic actioncontribute to its hypotriglyceridaemic action
Expert Opin. Pharmacother. (2008) 9(8):1397-1406
Telmisartan: Reverse Telmisartan: Reverse Cholesterol TransportCholesterol Transport
Excessive cholesterol in non-hepatic peripheral Excessive cholesterol in non-hepatic peripheral cells triggers efflux of free cholesterol from these cells triggers efflux of free cholesterol from these cells to liver by binding to HDLcells to liver by binding to HDL
This reverse cholesterol transport, regulates This reverse cholesterol transport, regulates cholesterol catabolism and is mediated by the cholesterol catabolism and is mediated by the ATP-binding cassette (ABC) transporters ABCA1, ATP-binding cassette (ABC) transporters ABCA1, ABCG1, ABCG5 and ABCG8 ABCG1, ABCG5 and ABCG8
Expert Opin. Pharmacother. (2008) 9(8):1397-1406
Telmisartan: Reverse Cholesterol Telmisartan: Reverse Cholesterol TransportTransport
ABCA1 is involved in HDL production and ABCA1 is involved in HDL production and mediates the cholesterol efflux from the mediates the cholesterol efflux from the periphery and its delivery to liverperiphery and its delivery to liver
Telmisartan induced ABCA1 gene expressionTelmisartan induced ABCA1 gene expression
Telmisartan may accelerate reverse cholesterol Telmisartan may accelerate reverse cholesterol transport through activation of ABCA1, leading to transport through activation of ABCA1, leading to total cholesterol and LDL-cholesterol loweringtotal cholesterol and LDL-cholesterol lowering
Expert Opin. Pharmacother. (2008) 9(8):1397-1406
Telmisartan: Lipid Lowering Telmisartan: Lipid Lowering MechanismMechanism
Liver X receptor α (LXR α ) plays a crucial role in the Liver X receptor α (LXR α ) plays a crucial role in the regulation of regulation of cholesterol efflux from enterocytes back cholesterol efflux from enterocytes back into the intestinal lumeninto the intestinal lumen via ABCA1 and ABCG5/G8 via ABCA1 and ABCG5/G8
Both PPAR- α and PPAR- γ upregulate LXR α gene Both PPAR- α and PPAR- γ upregulate LXR α gene expressionexpression and may indirectly regulate ABCA1 and and may indirectly regulate ABCA1 and ABCG5/G8 , resulting in inhibition of intestinal ABCG5/G8 , resulting in inhibition of intestinal cholesterol absorption cholesterol absorption
Inhibition of net cholesterol absorption may be one of Inhibition of net cholesterol absorption may be one of the possible mechanisms by which Telmisartan the possible mechanisms by which Telmisartan lowers total cholesterol and LDL-cholesterol levels via lowers total cholesterol and LDL-cholesterol levels via its PPAR- γ –activating effectits PPAR- γ –activating effect
Expert Opin. Pharmacother. (2008) 9(8):1397-1406
Expert Opin. Pharmacother. (2008) 9(8):1397-1406
Overview : Mechanism of Cardiovascular Overview : Mechanism of Cardiovascular Protection by TelmisartanProtection by Telmisartan
Expert Opin. Pharmacother. (2008) 9(8):1397-1406
ConclusionsConclusions
Telmisartan has Telmisartan has Anti-hypertensive action: Anti-hypertensive action: – highly selective for the AT1 receptorhighly selective for the AT1 receptor– long duration of action because of its long terminal long duration of action because of its long terminal
elimination half-lifeelimination half-life
Telmisartan- Unique property of activating PPAR- γ, Telmisartan- Unique property of activating PPAR- γ, improving insulin sensitivity and reducing triglyceride improving insulin sensitivity and reducing triglyceride levelslevels
Improves insulin sensitivityImproves insulin sensitivity
Decreases adipocyte cell sizeDecreases adipocyte cell size
Decrease hepatic fat storageDecrease hepatic fat storage
ConclusionsConclusions
Improvement in metabolic syndrome & reduction Improvement in metabolic syndrome & reduction of atherosclerosis riskof atherosclerosis risk
Decreased serum glucose and serum triglyceride Decreased serum glucose and serum triglyceride levels, and increased glucose uptake and GLUT4 levels, and increased glucose uptake and GLUT4 protein expressionprotein expression
Telmisartan associated:Telmisartan associated:– Significant reduction in left ventricular mass Significant reduction in left ventricular mass
indexindex– Posterior and septal wall thickness, in mild-to-Posterior and septal wall thickness, in mild-to-
moderate LVHmoderate LVH
ConclusionConclusion
Telmisartan valuable treatment option in the Telmisartan valuable treatment option in the management of hypertension and cardiovascular management of hypertension and cardiovascular riskrisk
Doctors and patients appreciate its excellent Doctors and patients appreciate its excellent safety profilesafety profile
ConclusionConclusion
The consistent antihypertensive efficacy during The consistent antihypertensive efficacy during
the entire 24 hr dosage interval and sustained the entire 24 hr dosage interval and sustained
BP lowering effect in the long term, combined BP lowering effect in the long term, combined
with its favorable tolerability profile, mean that with its favorable tolerability profile, mean that
telmisartan is a valuable first line treatment telmisartan is a valuable first line treatment
option for the management of essential option for the management of essential
hypertensionhypertension
Why combination therapy ?Why combination therapy ?
Multiple mechanisms involved in the pathogenesis Multiple mechanisms involved in the pathogenesis of hypertensionof hypertension
Effective BP control seen in only 50% of patients Effective BP control seen in only 50% of patients on monotherapy;on monotherapy;
BP goals difficult to attain with monotherapy in BP goals difficult to attain with monotherapy in patients with diabetes or target organ damagepatients with diabetes or target organ damage
combination therapy results in a much higher combination therapy results in a much higher responder rate (>80%)responder rate (>80%)
Hypertension: combination therapyHypertension: combination therapy
What is the need?What is the need?
JNC -7 recommends initiating combination therapy if:JNC -7 recommends initiating combination therapy if:
BP > 20/10 mm Hg above goal BPBP > 20/10 mm Hg above goal BP
( < 140/90)( < 140/90)
In diabetic hypertensivesIn diabetic hypertensives
In patients with chronic renal diseaseIn patients with chronic renal disease
Goal < 130/80
Combination therapy for hypertension Combination therapy for hypertension
With any single drug, not more than 25–50% of With any single drug, not more than 25–50% of hypertensives achieve adequate blood pressure controlhypertensives achieve adequate blood pressure control
J Hum. Hypertens 1995; 9:S33–S36J Hum. Hypertens 1995; 9:S33–S36
For patients not responding adequatelyto low doses of monotherapy
Increase the dose of drug. This, however, may lead to
increased side effects
Substitute with another drug from a different class
Add a second drug from a different class
(Combination therapy)
Add second drug from different class (Combination therapy)
If inadequate response obtained
Hypertension: combination therapyHypertension: combination therapy
Requirement of combination therapy:Requirement of combination therapy:
Both drugs must have Both drugs must have different mechanismsdifferent mechanisms of of
actionaction..
Combination should be Combination should be more effectivemore effective than than
monotherapy- additive/synergistic effectmonotherapy- additive/synergistic effect
Matching kinetics-Matching kinetics-
No adverse drug interactionsNo adverse drug interactions
No additive side effects.No additive side effects.
Hypertension: combination therapyHypertension: combination therapy
Beneficial combinations:Beneficial combinations:
Beta blocker + DiureticBeta blocker + Diuretic
ACEI /ARB + DiureticACEI /ARB + Diuretic
CCB + Beta blockerCCB + Beta blocker
CCB+ ACE-I /ARBCCB+ ACE-I /ARB
A or B + C or D
Hypertension: combination therapyHypertension: combination therapy
Benefits:Benefits:
Improved control of BP - Better target organ Improved control of BP - Better target organ
protection protection [response rate increase from 50% to 80%][response rate increase from 50% to 80%]
Better tolerated- Reduced side effects - Lower dose Better tolerated- Reduced side effects - Lower dose
of individual drugsof individual drugs
Improve patients compliance-Improve patients compliance- Reduced pill burdenReduced pill burden
EconomicalEconomical
Hypertension: combination therapyHypertension: combination therapy
Candidates:Candidates:
Stage 2 hypertensives: Stage 2 hypertensives: >>160/100160/100
Diabetic hypertensivesDiabetic hypertensives
Chronic renal diseaseChronic renal disease
Suggested guidelines for the use of Suggested guidelines for the use of fixed-dose combinationsfixed-dose combinations
Coexisting conditionCoexisting condition First choiceFirst choice
Ischaemic heart diseaseIschaemic heart disease Amlodipine + AtenololAmlodipine + Atenolol
DiabetesDiabetes Amlodipine +ACEI/ ARBAmlodipine +ACEI/ ARB
Congestive heart failureCongestive heart failure ACEI/ ARB + HCTZACEI/ ARB + HCTZ
TachycardiaTachycardia Amlodipine + Atenolol Amlodipine + Atenolol
Elderly hypertensivesElderly hypertensives Amlodipine + HCTZ Amlodipine + HCTZ ACEI/ ARB + HCTZACEI/ ARB + HCTZ
Renal insufficiencyRenal insufficiency (not due to renal (not due to renal Amlodipine + ACEI/ ARB Amlodipine + ACEI/ ARB artery stenosis)artery stenosis)
Combination TherapyCombination TherapyStrategy for improving efficacy Strategy for improving efficacy
and reducing side effectsand reducing side effects
Angiotensin II Receptor Blocker Angiotensin II Receptor Blocker (ARB)/Diuretic Combination(ARB)/Diuretic Combination
Diuretics ARBs
Fluid volume ( Preload)
Renin release
RAAS activation
PVR & preload via inhibition of action of AT II at the receptor level
RAAS suppression
Telmisartan/HydrochlorothiazideTelmisartan/HydrochlorothiazideParameterParameter TelmisartanTelmisartan HCTZHCTZ Tellzy-HTellzy-H
MOAMOA AT1 Receptor AT1 Receptor BlockerBlocker
DiureticDiuretic Complementary Complementary effecteffect
Pre load ( Blood Pre load ( Blood Volume)Volume)
DecreaseDecrease DecreaseDecrease Additive effectAdditive effect
After Load (PVR)After Load (PVR) DecreaseDecrease DecreaseDecrease Additive effectAdditive effect
RAASRAAS SuppressionSuppression ActivationActivation Neutral effectNeutral effect
DosingDosing ODOD ODOD ODOD
Telmisartan/HydrochlorothiazideTelmisartan/Hydrochlorothiazide
ParameterParameter TelmisartanTelmisartan HCTZHCTZ Tellzy-HTellzy-H
Renin LevelsRenin Levels DecreaseDecrease IncreaseIncrease No ChangeNo Change
Potassium Potassium LevelsLevels
IncreaseIncrease DecreaseDecrease No ChangeNo Change
• No Risk of Electrolytic imbalance
• Improved tolerability
Tellzy-HTellzy-H
Candidates:Candidates:
• Stage 2 hypertensives: Stage 2 hypertensives: >>160/100160/100
• Diabetic hypertensivesDiabetic hypertensives
• Chronic renal diseaseChronic renal disease
Tellzy-HTellzy-H
DoseDose : : one tablet daily in the morningone tablet daily in the morning– No dose adjustment required in:No dose adjustment required in: elderly or mild to moderate renal impairment elderly or mild to moderate renal impairment
– Use with caution in hepatic dysfunctionUse with caution in hepatic dysfunction
– Dose should not exceed 40 mg /day+ Dose should not exceed 40 mg /day+ 12.5mg/day12.5mg/day
– Not recommended in severe hepatic Not recommended in severe hepatic impairmentimpairment
Telmisartan/HydrochlorothiazideTelmisartan/Hydrochlorothiazide
Advantages :Advantages :
– Better blood pressure controlBetter blood pressure control
– Lesser incidence of individual drug’s side-effectsLesser incidence of individual drug’s side-effects
– Neutralisation of side-effectsNeutralisation of side-effects
– Improved patient compliance- Reduced pill Improved patient compliance- Reduced pill
burdenburden
ConclusionConclusion
The consistent antihypertensive efficacy during the The consistent antihypertensive efficacy during the
entire 24 hr dosage interval and sustained BP lowering entire 24 hr dosage interval and sustained BP lowering
effect in the long term, combined with its favorable effect in the long term, combined with its favorable
tolerability profile, mean that telmisartan is a valuable tolerability profile, mean that telmisartan is a valuable
first line treatment option for the management of first line treatment option for the management of
essential hypertensionessential hypertension
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