Hypertension. Does it Matter What Medications We Use? Nishant K. Sekaran, M.D. M.Sc. Intermountain Heart Institute

Hypertension Does it Matter What Medications We Use? Nishant K. Sekaran, M.D. M.Sc. Intermountain Heart Institute

Hypertension 2017 Classification BP Category Systolic Diastolic Normal 120 and 80 Elevated 120-129 and 80 Stage 1 130 or 80-89 Stage 2 140 or 90

CV events avoided per 1000 SBP reduction (mm Hg) 5y CV risk (%) Blood Pressure Lowering Treatment Trialists Collaborative, Lancet, 2014

Blood Pressure Reduction 10-year ASCVD risk Benefit is constant across groups Magnitude of benefit ~ baseline risk ASCVD risk + BP level ~ most efficient

Blood Pressure Treatment 2017 Guidelines 10-year ASCVD risk Systolic pressure (IA) Diastolic pressure (IC) 10% 130 mmhg 80 mmhg <10% 140 mmhg 90 mmhg *ACC/AHA Pooled Cohort Equations (http://tools.acc.org/ascvd-risk-estimator/) Stage I = 130/80, stage II = 140/90

SPRINT Trial Baseline SBP <120 ASCVD mmhg risk better > 15% NEJM 2015;373:2103-2116

Blood Pressure Treatment 2017 Guidelines LOE Stage Blood pressure Recommendation I- C/EO IIa- C/EO 2 140/90 mmhg + >20/10 mmhg above goal 2 first-line agents 1 130/80 mmhg Single with dose titration and/or sequential addition

Case 1 52 male presents for second office visit with a blood pressure 145/92. ASCVD risk 6%. In addition to non-pharmacologic instructions, you prescribe: 1) Hydrochlorothiazide (HCTZ) 2) Carvedilol 3) Chlorthalidone 4) Amlodipine + HCTZ

Medication Therapy Primary Thiazide, ACEI/ARB, CCB ~ first-line Beneficial clinical outcomes Safe and tolerable

First-step strategy ALLHAT Trial (n=33,357 4.9 years) Chlorthalidone, amlodipine, or lisinopril RCT, double-blind, active control 1 ASCVD risk factor Outcomes 1- fatal CHD + non-fatal MI 2- mortality, CVA, all-chd, all-cvd

ALLHAT Trial MI risk Fatal CHD + non-fatal MI equivalent

ALLHAT Trial CVA risk Lisinopril stroke risk

ALLHAT Trial HF risk Chlorthalidone heart failure risk

ALLHAT Trial - % <140/90 Year Thiazide CCB ACEi p CCB v. T Baseline 27.2 27.6 26.3.56.12 p ACEi v. T 1 57.8 55.2 50.6 <.001 <.001 2 61 57.4 54.1 <.001 <.001 3 63.9 63.4 59.2.54 <.001 4 67.1 65.8 63.1.15 <.001 5 68.2 66.3 61.2.09 <.001

ALLHAT Trial % non-diabetic participants with serum glucose 126 mg/dl Year Thiazide CCB ACEi p CCB v. T p ACEi v. T 2 9.6 7.4 5.8.006 <.001 4 11.6 9.8 8.1.04 <.001

Stroke Prevention B-blocker higher CVA risk ~ thiazide

Stroke Prevention Calcium channel blockers Thiazide 1 (0.86, 1.2) ACE inhibitor 1.2 (1, 1.4) Beta blockers 1.4 (1.1, 1.7) ARB 1.1 (0.93, 1.4) Relative treatment effect (95% CI) compared to calcium channel blocker

Heart Failure Thiazide may be superior for HF prevention

Case 2 70 woman presents for second office visit with a blood pressure 152/92. ASCVD risk 13%. In addition to non-pharmacologic instructions, you prescribe: 1) Amlodipine + lisinopril 2) Carvedilol 3) Chlorthalidone 4) Amlodipine + HCTZ

Medication Therapy Strategy Monotherapy Combination

Low-Dose Combination Therapy Key points Increases efficacy Reduces adverse effects

Low-Dose Combination Therapy Meta-analysis (n=56,000) 5 major classes ~ similar (7.3 / 3.7 mmhg) ½ dose 20% standard efficacy BP additive AE low-dose < AE standard (AE not additive) BMJ 2003; 326: 1427-1431

Adverse Effects Medication Half-standard Standard Common Profile Thiazide 2.0 (-2.2-6.3) Beta blocker 5.5 (0.3-10) ACE-I 3.9 (-3.7-11.6) ARB -1.8 (-10.2-6.5) CCB 1.6 (-3.5-6.7) 9.9 (6.6-13.2) 7.5 (4.0-10.9) 3.9 (-0.5-8.3) 0 (-5.4-5.4) 8.3 (4.8-11.8) Dizzy, impotence, nausea, cramp Cold extremities, fatigue, nausea Cough - Flushing, ankle edema, dizzy

Combination strategy ACCOMPLISH Trial (n=11,056 3 years) Benezapril + amlodipine OR hydrochlorothiazide RCT, double-blind, industry sponsored Baseline high CV risk Outcomes 1-fatal/non-fatal CV events (hospitalization + revasc) 2-fatal/non-fatal MI/CVA only

Combination strategy ACCOMPLISH Trial (n=11,056 3 years) Outcomes Benezapril + amlodipine Benezapril + HCTZ RRR (95% CI) CV events 10% 12% 19% (9 27) NNT 45 (32 90) CV death + MI + CVA 5% 6.3% 20% (8 32) 78 (50 205) Ann Intern Med. 2009;150(10):JC5-8

Combination strategy ACCOMPLISH Critiques HCTZ not chlorthalidone SBP/DBP 0.9/1.1 mm Hg amlodipine ASA + lipid therapy < 70% both arms Regimen could include other agents

Secondary Stroke Prevention Hazard ratio = 1 The Lancet 2001; 358: 1033-41

Case 3 50 black male presents for second office visit with a blood pressure 142/95. ASCVD risk 8%. In addition to non-pharmacologic instructions, you prescribe: 1) Atenolol 2) Amlodipine 3) Diltiazem + chlorthalidone 4) Lisinopril

Race and Ethnicity Recommendation Strength In black patients without HF or CKD, including DM, initial treatment should be with a thiazide or calcium channel blocker 2 medications to achieve BP <130/80, especially in black patients IB-R IC-LD

Race and Ethnicity Lisinopril versus Chlorthalidone Outcome Heart failure Black RR (95% CI) 1.32 (1.11-1.58) Stroke 1.40 (1.17-1.68) Non-black RR (95% CI) 1.15 (1.01-1.30) 1 (0.85-1.17) JAMA 2002, ALLHAT

Case 4 32 G2P1A0 woman presents for second office visit with a blood pressure 144/92. ASCVD risk 2%. In addition to non-pharmacologic instructions, you prescribe: 1) Atenolol 2) Amlodipine 3) Labetalol 4) Lisinopril

Pregnancy Vasodilation BP until 3 rd and trimester SVR

Pregnancy Goals Prevent severe hypertension Prolong gestation to promote maturity

Pregnancy CHIPS Trial (n=987) Does tight BP control outcomes? Diastolic = 100 mmhg v. 85 mmhg 1- Pregnancy loss or high-risk neonate 2- Serious maternal complications

Pregnancy CHIPS Trial (n=987) Study protocol ~ labetalol 1 st line No ACE inhibitors, ARB, renin blocker, or atenolol

CHIPS Trial Tight DBP 85 mmhg Less tight DBP 105 mmhg Adjusted OR Primary 31.4 30.7 1.02 (0.77-1.35) Birth weight <10 percentile Serious maternal complications Severe hypertension* 16.1 19.7 0.78 (0.56-1.08) 3.7 2.0 1.74 (0.79-3.84) 40.6 27.5 1.80 (1.34-2.38) Pre-eclampsia 48.6 45.7 1.17 (0.88-1.47)

Case 5 64 year old male with a history of myocardial infarction 4 months ago presents with a blood pressure 138/86. LVEF 54%. In addition to non-pharmacologic instructions, you prescribe: 1) Atenolol 2) Amlodipine 3) Carvedilol 4) Chlorthalidone

Stable Ischemic Heart Disease Recommendation (SIHD + HTN) Goal BP <130/80 1 st BB, ACEi, or ARB 2 nd TZD, MRA, dihydropyridine (PRN) Strength IB/C IB/C >130/80, add CCB to BB IB MI or ACS, BB 3 years IIa

Medication Therapy Beta blockers Primary prevention less effective CV events Stroke Secondary prevention useful

Beta blockers Coronary artery disease <130/80 ~ 25% CV events + mortality Post-MI ~ 25% mortality 3 years therapy

Aortic Disease Recommendation Beta blockers preferred in hypertension with aortic disease With AR, treat hypertension with agents that do not slow the HR (avoid beta blockers) Strength IC IIa

Hypertenson Key Points ASCVD risk + BP ~ most efficient strategy Moderate dose combination therapy Establish relevant clinical context for medication selection