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Hypertension Evidence and CHS Guidelines

2005

Hypertension Evidence and CHS Guidelines

2005

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Evidence EvolutionEvidence Evolution

• Hard end-points– Mortality– CVD events– Cerebrovascular events– PVD events– CHF– Progression to ESRD

• Surrogate end-points– Rising CR– Progression to proteinuria– Progression/regression of micro-albuminuria

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Evidence EvolutionEvidence Evolution

• MRC-1985• HAPPHY-1987• EWPHE-1991• STOP-1991• SHEP-1991-4• STONE-1996• SYS-EUR-1997• SYS-CHINA-1996-98• HOT-1998• UKPDS -1998• CAPPP-1999• STOP 2 -1999

• HOPE -2000• MICRO-HOPE -2000• INSIGHT -2000• NORDIL -2000• CALM -2000• INDT -2001• IRMA -2001• RENAAL -2001• PROGRESS -2001• LIFE-2002• SCOPE 2002• ALLHAT 2002

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CHS Guideline Evolution 2002CHS Guideline Evolution 2002

• Impact of the ALLHAT - 2002

• Consideration of – PROGRESS - 2001– IDNT - 2001– RENAAL - 2001– ANBP2 - 2003

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2003

Canadian Hypertension Education Program Recommendations 37

Treat Hypertension in the Context of Overall Cardiovascular Risk

V high riskV high riskV high riskIV. ACC or Diabetes

V high riskHigh riskHigh riskIII. ≥3 risk factors or

TOD or De novo diabetes

V high riskMedium riskMedium riskII.1-2 risk factors

High riskMedium riskLow riskI.No other risk factors

SBP ? 180 or DBP ? 110

(severe hypertension)

SBP 160-179 or DBP 100-109

(moderate hypertension)

SBP 140-159 orDBP 90-99

(mild hypertension)

Other Risk Factors & Disease History

Grade 3Grade 2Grade 1

Adapted from WHO/ISH Recommendations on Hypertension.ChalmersJ et al.J Hyper1999;17:151-85.

Risk strata (typical % 10 year risk of stroke, myocardial infarction or death)

≥30%20-30%15-20%<15%

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Guideline Evolution 2004Guideline Evolution 2004

Hypertension• ALLHAT - 2002• LIFE - 2002• ANBP2 - 2003• OPTIMAAL - 2002• EPHESUS - 2003• CHARM - 2003• Psaty-Network meta-analysis• Law Meta-analysis• Staessen

Meta-regression analysis

Post stroke• PROGRESS - 2001

ASA and Statins • HOT - 1998• ASCOT-LLA - 2003• PROSPER - 2002• HPS - 2002• ALLHAT-LLT - 2002

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CHS January 2004Indications for drug therapy in adults with hypertension

without compelling indications for specific agents:

CHS January 2004Indications for drug therapy in adults with hypertension

without compelling indications for specific agents:

1. Strongly consider antihypertensive therapy if DBP ≥ 90 with TOD or CV risk factors

– Elevated SBP, smoking, dyslipidemia, strong FH CAD, truncal obesity, sedentary lifestyle

2. Rx antihypertensive therapy for DBP ≥ 100 or SBP ≥ 160 without TOD or CV risk factors

3. Rx statin therapy in HTN patients > 40 yr of age with 3 or more CV risk factors or established atherosclerotic disease

4. Strongly consider low dose ASA in HTN patients > 50 yr of age. (Caution if BP not controlled)

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Cardiovascular risk factors for consideration of statintherapy in non-hyperlipidemic patients with hypertension

(derived from ASCOT-LLA)

• Male• Age 55 years or older• Left ventricular

hypertrophy• Other electrocardiogram

abnormalities:– left bundle branch block,

left ventricular strain pattern, abnormal Q waves

– or ST-T changes compatible with ischemic heart disease

• Peripheral arterial disease

• Previous stroke or transient ischemic attack

• Microalbuminuria or proteinuria

• Diabetes mellitus

• Smoking

• Family history of premature cardiovascular disease

• TC/HDL ≥ 6

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CHS January 2004Recommendations for individuals with diastolic hypertension

with or without systolic hypertension. Initial therapy:

CHS January 2004Recommendations for individuals with diastolic hypertension

with or without systolic hypertension. Initial therapy:

• Grade A: – thiazide diuretics

• Grade B: -blockers (in those

younger than 60 years)– ACE inhibitors (in

non-Blacks)– long-acting

dihydropyridine CCBs– angiotensin receptor

antagonists (ARBs)

• If adverse effects substitute another drug from this group

• Avoid hypokalemia: Use K sparing diuretic with thiazides

• Use combination therapy if partial response

• Add other classes if poor control - blocker, centrally acting

agents or non-DHP CCB - blocker not recommended as

first line agents

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CHS January 2004Recommendations for individuals with

Isolated Systolic Hypertension Initial therapy:

CHS January 2004Recommendations for individuals with

Isolated Systolic Hypertension Initial therapy:

• Grade A: – thiazide diuretics– long-acting dihydropyridine

CCBs

• Grade B: – angiotensin receptor

antagonists (ARBs)

• If adverse effects substitute another drug from this group

• Avoid hypokalemia: Use K sparing diuretic with thiazides

• Use combination therapy if partial response

• Add other classes if poor control or adverse effects - blocker, ACE inhibitors,

centrally acting agents or non-DHP CCB

-blockers and -blockers are not recommended as first line agents

CHS January 2004CHS January 2004Considerations for individualization of anti-hypertensive therapyConsiderations for individualization of anti-hypertensive therapy

Indication Initial Therapy Second line Rx Notes/Cautions

DM with nephropathy ACE-i or ARB addition thiazide, * -blockers , LA-CCB, ACE/ARB combo

*Cardioselective -blockers

If CR >150 mmol/l use loop diuretic for volume control

DM without

nephropathy

ACE-i or ARB

or thiazide

Combo1st line Rx or *-blockers, LA-CCB

Angina -blockers + strongly consider ACE-i

LA-CCB Avoid short acting nifedipine

Prior MI -blockers + ACE-i Combine additional Rx

CHF -blockers + ACE-i + spironolactone (ARB if ACE-i intolerant )

Hydralazine /ISDN: thiazide or loop diuretics as additive therapy

Avoid non DHP-CCB

(diltiazem, verapamil)

Prior CVA or TIA ACE-i/diuretic combination

BP reduction recurrent events

Renal Disease ACE-i/diuretic as additive Rx

ARB if ACE-i intolerant

Combo other agents

Avoid ACE-i if bilateral Renal artery stenosis

LVH ACE-I, ARBs, DHP-CCB, thiazide, -blockers < 55 yr

Avoid hydralazine and minoxidil

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Guideline Evolution 2005Guideline Evolution 2005

• SHEAF Study• Ohasama Cohort• OvA Study• Staessen et al• Thijs et al• VALUE• ACTION• INVEST • VALIANT• BP Lowering Treatment Trialists Collaboration

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Guideline Evolution 2005Guideline Evolution 2005

• Key Messages– Expedited diagnosis of hypertension (HTN)– Use any validated technology to diagnose HTN

• Office BP

• Ambulatory BP

• Self/Home BP

– Focus on BP control rather than preferred “first line” agent

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Guideline Evolution 2005Guideline Evolution 2005

• Integrate global CVD management into HTN management plan

• Lifestyle modifications are key

• Combination therapies (lifestyle and Rx) to achieve target

• Focus on adherence

16

Choice of Pharmacological Treatment

Associated risk factors?or

Target organ damage/complications?or

Concomitant diseases/conditions?

IndividualizedTreatment

(with compelling indications)

YES

Treatment in theabsence of compelling

indication

NO

17

Choice of pharmacological treatment for hypertensive patients without other compelling indications:

Treatment of Systolic Diastolic hypertension

Treatment of Isolated Systolic hypertension

18

Treatment of Adults with Systolic-Diastolic Hypertension without Other Compelling Indications

INITIAL TREATMENT AND MONOTHERAPY

* Not indicated as first line therapy over 60

Beta-blocker*

Long-actingCCB

Thiazide ACE-I ARB

Lifestyle modificationtherapy

TARGET <140 mm Hg systolic and < 90 mmHg diastolic

19

Combination Therapy for Systolic-Diastolic Hypertension without Other Compelling Indications

CONSIDER

• Nonadherence?• Secondary HTN?• Interfering drugs or lifestyle?• White coat effect?• Resistant Hypertension?

If blood pressure is still not controlled, or there are adverse effects, other classes of antihypertensive drugs may be combined (such as alpha blockers, centrally acting agents, or nondihydropyridine calcium channel blocker).

2. Triple or Quadruple Therapy

1. Dual Combination Therapy

If partial response to monotherapy

20

Summary: Treatment of Systolic-Diastolic Hypertension without Other Compelling Indications

* Not indicated as first line therapy over 60

CONSIDER

• Nonadherence?• Secondary HTN?• Interfering drugs or

lifestyle?• White coat effect?

Dual Combination

Triple or Quadruple Therapy

Lifestyle modificationtherapy

Thiazidediuretic ACE-I Long-acting

CCBBeta-

blocker* ARB

TARGET <140 mm Hg systolic and < 90 mmHg diastolic

21

Choice of pharmacological treatment for hypertensive patients with other compelling indications

Treatment of diastolic-systolic hypertension

Treatment of isolated systolic hypertension

22

Treatment Algorithm for Isolated Systolic Hypertension without Other Compelling Indications

INITIAL TREATMENT AND MONOTHERAPY

Thiazide diuretic

Long-actingDHP CCB

Lifestyle modificationtherapy

ARB

TARGET <140 mmHg Systolic BP

23

Summary: Treatment of Isolated Systolic Hypertension without Other Compelling Indications

CONSIDER

• Nonadherence?• Secondary HTN?• Interfering drugs or

lifestyle?• White coat effect?

Thiazide diuretic

Long-actingDHP CCB

Dual combination

Triple or Quadruple* combination

Lifestyle modificationtherapy

ARB

TARGET <140 mmHg Systolic BP

*If blood pressure is still not controlled, or there are adverse effects, other classes of antihypertensive drugs may be combined (such as alpha blockers, centrally acting agents, or nondihydropyridine calcium channel blocker).

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Anti-Hypertensive Therapeutic Classification

Anti-Hypertensive Therapeutic Classification

ACE inhibitor

ARB

(K sparing)

DIURETIC(Thiazide)

-blocker*

Long Acting CCB*

*Caution combining non-DHP-CCB (especially verapamil) with a -blocker

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First Line Therapy First Line Therapy

ACE inhibitor

ARB

(K sparing)

DIURETIC(Thiazide)

-blocker*

Long Acting CCB*

*Caution combining non-DHP-CCB (especially verapamil) with a -blocker

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Systolic/Diastolic HTN Systolic/Diastolic HTN

ACE inhibitor

ARB

-blocker* (K sparing)

DIURETIC(Thiazide)

Long Acting CCB*

*Caution combining non-DHP-CCB (especially verapamil) with a -blocker

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Post-CVA or TIAPost-CVA or TIA

ACE inhibitor

ARB

-blocker*

*Caution combining non-DHP-CCB (especially verapamil) with a -blocker

Long Acting CCB*

(K sparing)

DIURETIC(Thiazide)

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Isolated Systolic HTN-Elderly Isolated Systolic HTN-Elderly

ACE inhibitor

ARB

-blocker

Long Acting

DHP-CCB

(K sparing)

DIURETIC(Thiazide)

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Isolated Systolic HTN-Elderly Isolated Systolic HTN-Elderly

ACE inhibitor/

ARB

-blocker

Long Acting

DHP-CCB

(K sparing)

DIURETIC(Thiazide)

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CAD - Chronic AnginaCAD - Chronic Angina

ACE inhibitor

ARB

-blocker*

Consider adding ACE-I for all patients with documented CAD (Grade A) based on

HOPE and EUROPA

Long Acting CCB*

*Caution combining non-DHP-CCB (especially verapamil) with a -blocker

(K sparing)

DIURETIC(Thiazide)

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CAD-Recent MI or LV Dysfunction

CAD-Recent MI or LV Dysfunction

ACE inhibitor

-blocker*

Long Acting CCB*

*Caution combining non-DHP-CCB (especially verapamil) with a -blocker

(K sparing)

DIURETIC(Thiazide)

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CHF + HTNCHF + HTN

ACE inhibitor

ARB if ACE intolerant

DIURETIC (loop/spironolactone)

-blocker

Long Acting

DHP-CCB

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DM without NephropathyBP Target < 130/80

DM without NephropathyBP Target < 130/80

ACE inhibitor

or ARB

-blocker*

(K sparing)

DIURETIC or

(Thiazide)

Long Acting CCB*

*Caution combining non-DHP-CCB (especially verapamil) with a -blocker

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DM with Nephropathy First line therapy:

DM with Nephropathy First line therapy:

ACE inhibitor

or ARB

-blocker*

(K sparing)

DIURETIC

(Thiazide)

Long Acting CCB*

*Caution combining non-DHP-CCB (especially verapamil) with a -blocker

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DM with Nephropathy Second line therapy:

DM with Nephropathy Second line therapy:

ACE inhibitor

or ARB

-blocker*

(K sparing)

DIURETIC

(Thiazide)

*Caution combining non-DHP-CCB (especially verapamil) with a -blocker

Long Acting CCB*

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DM with Nephropathy Second line therapy:

DM with Nephropathy Second line therapy:

ACE inhibitor

or ARB

Cardioselective

-blocker*

(K sparing)

DIURETIC

(Thiazide)

*Caution combining non-DHP-CCB (especially verapamil) with a -blocker

Long Acting CCB*

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(K sparing)

DIURETIC

(Thiazide)

DM with Nephropathy Second line therapy:

DM with Nephropathy Second line therapy:

ACE inhibitor

or ARB

-blocker*

*Caution combining non-DHP-CCB (especially verapamil) with a -blocker

Long Acting CCB*

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(K sparing)

DIURETIC

(Thiazide)

DM with Nephropathy Second line therapy:

DM with Nephropathy Second line therapy:

ACE inhibitor

and ARB

-blocker*

*Caution combining non-DHP-CCB (especially verapamil) with a -blocker

Long Acting CCB*

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Non-diabetic NephropathyBP Target < 125/75

Non-diabetic NephropathyBP Target < 125/75

ACE inhibitor

ARB if ACE intolerant

-blocker*

DIURETIC (Thiazide or loop)

As additive

therapy

*Caution combining non-DHP-CCB (especially verapamil) with a -blocker

Long Acting CCB*

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See www.hypertension.ca for Complete Recommendations

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Global Vascular Protection for Patients with Hypertension

Global Vascular Protection for Patients with Hypertension

• Diet (DASH)• Weight loss (waist < 102 cm M and 88 cm F)• Exercise- 30 to 60 min 4-7 days/week• Smoking Cessation• Moderate Alcohol intake• Low dose ASA if BP controlled• Statin• ACE inhibitors for established vascular disease• ACE inhibitors or ARBs for diabetics or patients with

kidney disease

42

Important Messages for the Management of Hypertension

Expedite the diagnosis of hypertension Assess the risk Treat to target

Lifestyle Combination therapy

Promote adherence

43

Summary

Hypertension is a major factor responsible for progression of atherosclerotic disease. Therefore, a comprehensive treatment of hypertension should aim at CV risk reduction strategies, including management of all associated risk factors.