2017 Updates in Cardiology

How do you manage hypertension when meds don’t work?

Santanu Biswas March 4, 2017

Disclosures

• None

First things first

Causes of Inadequate Responsiveness to Therapy •Non-adherence

• Pseudo-resistance • White coat

• Drug-related causes • NSAIDS • Sympathomimetics (Nasal

decongestants, appetite suppressants, cocaine, caffeine)

• Oral contraceptives • Adrenal steroids • EPO

• Associated conditions • Smoking • Obesity • Sleep apnea • Insulin resistance • Alcohol • Anxiety • Chronic pain

• Volume • Sodium • Kidney injury • Inadequate diuretic therapy

Compliance

Compliance

• “the extent to which the patient’s behavior coincides with the clinical prescription”

Haynes RB, Taylor DW, Sackert DL, eds. Compliance in Health Care. Baltimore, D: Johns Hopkins University Press; 1979.

Adherence

• A behavioral process, strongly influenced by • the environment in which patients live • health care providers practice • health care systems deliver care

• Non-adherence can refer to a breakdown of any of these issues • Ie physician inertia

Adherence vs Compliance

• Solutions to non-compliance • Pill-boxes • Regimen simplification • Assess patient knowledge deficits

• Solutions to non-adherence • Address provider bias or inertia • Apply office based practices to increase patient touches • Employ community resources such as community pharmacists to

communicate blood pressure to the office • Petition payors for financial support for home blood pressure devices

32 year old female: March 2016

• Blood pressure (automated cuff) 200/100

• Labetalol 200mg twice daily • Arm circumference: 44 cm • Height: 66 inches • Weight 283 pounds • BMI 44

A couple of points about technique

AHA statement

• For accurate blood pressure measurement, the provider must: • be properly trained in the techniques of blood pressure measurement • use an accurate and properly maintained device • recognize subject factors, such as anxiety and recent nicotine use, that

would adversely affect blood pressure measurements; • position the subject appropriately • select the correct cuff and position it correctly

Proper technique

• Subject preparation • Remove clothing (sleeve should not tourniquet arm) • Comfortably seated • Back and arm is supported. Legs not crossed

• Cuff size • Bladder LENGTH is at least 80% of arm circumference. (Bladder

length is hidden inside cuff) • Bladder WIDTH is at least 40% of arm circumference

Where is the bladder?

80%

40%

32 year old pregnant female: March 2016

• Blood pressure (automated cuff) 200/100

• Labetalol 200mg twice daily • Arm circumference: 44 cm • Height: 66 inches • Weight 283 pounds • BMI 44

32 year old pregnant female: March 2016

• Thigh cuff used: BP 150/80 • Labetalol slowly titrated up to 600mg twice daily and nifedipine

30mg once daily added over the next several months.

Let’s Ban Automated BP Cuffs!!

Mercury Sphygmomanometer

• “Gold standard”? • Banned in VA hospitals

Manual vs Oscillometric BP

Am J Cardiol 2010;106:386 –388

Sys-Eur Trial (1997)

• Elderly patients > 60 years treated with ISH treated with nifedipine/enalapril/HCTZ to < 150 mm Hg

• The prevalence of use of terminal digit zero reduced from an average of 42.4% in the year prior to the date when a center first randomized a patient to 22% at the year 6

• A higher than expected prevalence of the SBP value of 148 mmHg was found in the active treatment groups in the double-blind phase.

• Selection for 148 mmHg persisted over time

Selected trials using oscillometry

• HOT trial (1999). 19193 patients • Lowering DBP in patients with diabetes to levels below 80 mm Hg

decreases the risk of MACE and CV mortality compared with lowering it to "normal" (< 90 mm Hg) levels.

• ACCORD trial (2008). 4733 patients • In patients with DM II at high risk for CV events, BP target < 120 mm

Hg, compared with < 140 mm Hg 140 mm Hg, did not reduce the rate of a composite outcome of fatal and nonfatal major cardiovascular events

• Sprint trial (2015). 9361 patients

AHA statement

• For accurate blood pressure measurement, the observer must: • be properly trained in the techniques of blood pressure measurement • use an accurate and properly maintained device • recognize subject factors, such as anxiety and recent nicotine use, that

would adversely affect blood pressure measurements; • position the subject appropriately • select the correct cuff and position it correctly • perform the measurement using the auscultatory or automated

oscillometric method and accurately record the values obtained • Observer error is a major limitation of the auscultatory

method

Oscillometry caveats

• Atrial fibrillation • Obesity

32 year old female: March 2016

• Blood pressure (manual cuff) 200/100

• Labetalol 200mg twice daily • Complains of near syncope

when taking BP medicine • Arm circumference: 44 cm • Height: 66 inches • Weight 283 pounds • BMI 44

32 year old female: March 2016

• Thigh cuff used: BP 150/80 • Labetalol slowly titrated up to 600mg twice daily and nifedipine

30mg once daily added over the next several months.

32 year old female: September 2016

• Arm oscillometric cuff: 180/79 • Thigh manual cuff: 120/60 • Blinded second provider obtained similar measurements

68 year old male

• BP 158/96 • Sleep apnea, wears CPAP • No renal artery stenosis • DM • BP regimen: chlorthalidone 25mg once daily, benazepril 40mg

once daily, carvedilol 25mg twice daily, clonidine 0.2mg three times daily

Definitions

• Essential (primary) hypertension (I10) • Controlled resistant hypertension • Uncontrolled resistant hypertension • Refractory hypertension • Malignant hypertension

Resistant Hypertension: Definitions

• Uncontrolled RH is defined as BP above goal on a regimen consisting of 3 or more drugs with complementary mechanisms of action at optimal doses and preferably including a diuretic

• Controlled RH has been defined as those patients whose BP is controlled by 4 or more drugs at optimal doses, preferably a diuretic

JASH, Volume 8 , Issue 10 , 743 - 757

Resistant Hypertension: Definitions

• Refractory Hypertension. Uncontrolled hypertension with five or more drugs including chlorthalidone and a mineralocorticoid receptor antagonist

Laboratory Findings

• Aldosterone 23 ng/dl (nl < 20 ng/dl) • Renin <0.1

68 year old male

• Spironolactone 25mg once daily started • Blood pressure: 120/72

82 year old female

• Blood pressure. 219/142 • Clinic Blood pressures

• 7/26/16. 172/86; 11/10/15. 162/80; 12/3/14 180/86 • Cannot tolerate telmisartan, hydrochlorothiazide, Lisinopril,

amlodipine, verapamil, nebivolol, aliskiren, losartan, olmisartan, clonidine, carvedilol, clonidine, hydralazine, chlorthalidone, isosorbide mononitrate

• No renal artery stenosis • Aldosterone 74 ng/dL • Renin 1.8

82 year old female

• Aldosterone 25mg once daily started • Home BP log

8/26 8/27 8/29 8/30 9/1 9/2 9/3 9/4 9/5 9/6

147/95 154/105 114/85 149/99 139/76 129/99 117/89 163/93 154/110 138/88

Hyperaldosteronism

• Renin independent hyperaldosteronism is felt to be an underdiagnosed but relative common cause of hypertension (5-10%)

• The most frequent causes of primary aldosteronism include: • Bilateral idiopathic hyperaldosteronism (60-70%) • Unilateral aldosterone producing adenoma’s (30-40%)

• Patients with adrenal hyperplasia are often not hypokalemic

80 year old female

• Clinic blood pressure. 140/84 • Repeat office BP. 140/80 • She has tried losartan-hydrochlorothiazide, bisoprolol-

hydrochlorothizide, and ramipril with near-syncope • She does not want to start another blood pressure medicine

APBM 8/17/16

• Mean 24 hr 139/68 • Mean daytime 144/70 • Mean nighttime 126/65

ABPM

NICE Rationale for ABPM

• The analysis for the guideline found the use of ABPM to be both cost-effective and cost-saving, due to improved diagnostic accuracy and fewer people being treated inappropriately

• Multiple assessments of blood pressure may delay the start of treatment for several weeks or months, and in some cases years, if the patient fails to return for follow-up

APBM 8/17/16

• Mean 24 hr 139/68 • Mean daytime 144/70 • Mean nighttime 126/75 • Normal <135/75

Adapt from Figure 2B in the N Engl J Med manuscript

Include NNT

All-cause Mortality Cumulative Hazard

Hazard Ratio = 0.73 (95% CI: 0.60 to 0.90)

During Trial (median follow-up = 3.26 years) Number Needed to Treat (NNT) to Prevent a death = 90

Standard (210 deaths)

Intensive (155 deaths)

Number of Participants

Intensive Standard

No. of Events Rate, %/year No. of Events Rate, %/year HR (95% CI) P value

Primary Outcome 243 1.65 319 2.19 0.75 (0.64, 0.89) <0.001

All MI 97 0.65 116 0.78 0.83 (0.64, 1.09) 0.19

Non-MI ACS 40 0.27 40 0.27 1.00 (0.64, 1.55) 0.99

All Stroke 62 0.41 70 0.47 0.89 (0.63, 1.25) 0.50

All HF 62 0.41 100 0.67 0.62 (0.45, 0.84) 0.002

CVD Death 37 0.25 65 0.43 0.57 (0.38, 0.85) 0.005

Serious Adverse Events* (SAE) During Follow-up

All SAE reports

Number (%) of Participants Intensive Standard HR (P Value)

1793 (38.3) 1736 (37.1) 1.04 (0.25)

SAEs associated with Specific Conditions of Interest

Hypotension 110 (2.4) 66 (1.4) 1.67 (0.001) Syncope 107 (2.3) 80 (1.7) 1.33 (0.05) Injurious fall 105 (2.2) 110 (2.3) 0.95 (0.71) Bradycardia 87 (1.9) 73 (1.6) 1.19 (0.28) Electrolyte abnormality 144 (3.1) 107 (2.3) 1.35 (0.020) Acute kidney injury or acute renal failure 193 (4.1) 117 (2.5) 1.66 (<0.001)

*Fatal or life threatening event, resulting in significant or persistent disability, requiring or prolonging hospitalization, or judged important medical event.

Number (%) of Participants with a Monitored Clinical Measure During Follow-up

Number (%) of Participants Intensive Standard HR (P Value)

Laboratory Measures1 Sodium <130 mmol/L 180 (3.9) 100 (2.2) 1.76 (<0.001) Potassium <3.0 mmol/L 114 (2.5) 74 (1.6) 1.50 (0.006) Potassium >5.5 mmol/l 176 (3.8) 171 (3.7) 1.00 (0.97)

Signs and Symptoms Orthostatic hypotension2 777 (16.6) 857 (18.3) 0.88 (0.013) Orthostatic hypotension with dizziness 62 (1.3) 71 (1.5) 0.85 (0.35)

1. Detected on routine or PRN labs; routine labs drawn quarterly for first year, then q 6 months 2. Drop in SBP ≥20 mmHg or DBP ≥10 mmHg 1 minute after standing (measured at 1, 6, and 12 months and yearly thereafter)

Lancet 2016; 388: 2142–52

CLARISA Registry

J Am Coll Cardiol. 2016 Oct 18;68(16):1713-1722