Hypertension. Does it Matter What Medications We Use? Nishant K. Sekaran, M.D. M.Sc. Intermountain Heart Institute
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1 Hypertension Does it Matter What Medications We Use? Nishant K. Sekaran, M.D. M.Sc. Intermountain Heart Institute
2 Hypertension 2017 Classification BP Category Systolic Diastolic Normal 120 and 80 Elevated and 80 Stage or Stage or 90
3 CV events avoided per 1000 SBP reduction (mm Hg) 5y CV risk (%) Blood Pressure Lowering Treatment Trialists Collaborative, Lancet, 2014
4 Blood Pressure Reduction 10-year ASCVD risk Benefit is constant across groups Magnitude of benefit ~ baseline risk ASCVD risk + BP level ~ most efficient
5 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 ( Stage I = 130/80, stage II = 140/90
6 SPRINT Trial Baseline SBP <120 ASCVD mmhg risk better > 15% NEJM 2015;373:
7 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
8 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
9 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
10 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 ( Stage I = 130/80, stage II = 140/90
11 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
12 Medication Therapy Primary Thiazide, ACEI/ARB, CCB ~ first-line Beneficial clinical outcomes Safe and tolerable
13 First-step strategy ALLHAT Trial (n=33, 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
14 ALLHAT Trial MI risk Fatal CHD + non-fatal MI equivalent
15 ALLHAT Trial CVA risk Lisinopril stroke risk
16 ALLHAT Trial HF risk Chlorthalidone heart failure risk
17 ALLHAT Trial - % <140/90 Year Thiazide CCB ACEi p CCB v. T Baseline p ACEi v. T <.001 < <.001 < < < <.001
18 ALLHAT Trial % non-diabetic participants with serum glucose 126 mg/dl Year Thiazide CCB ACEi p CCB v. T p ACEi v. T < <.001
19 Stroke Prevention B-blocker higher CVA risk ~ thiazide
20 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
21 Heart Failure Thiazide may be superior for HF prevention
22 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
23 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
24 Medication Therapy Strategy Monotherapy Combination
25 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
26 Low-Dose Combination Therapy Key points Increases efficacy Reduces adverse effects
27 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:
28 Adverse Effects Medication Half-standard Standard Common Profile Thiazide 2.0 ( ) Beta blocker 5.5 (0.3-10) ACE-I 3.9 ( ) ARB -1.8 ( ) CCB 1.6 ( ) 9.9 ( ) 7.5 ( ) 3.9 ( ) 0 ( ) 8.3 ( ) Dizzy, impotence, nausea, cramp Cold extremities, fatigue, nausea Cough - Flushing, ankle edema, dizzy
29 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
30 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
31 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
32 Secondary Stroke Prevention Hazard ratio = 1 The Lancet 2001; 358:
33 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
34 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
35 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
36 Race and Ethnicity Lisinopril versus Chlorthalidone Outcome Heart failure Black RR (95% CI) 1.32 ( ) Stroke 1.40 ( ) Non-black RR (95% CI) 1.15 ( ) 1 ( ) JAMA 2002, ALLHAT
37 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
38 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
39 Pregnancy Vasodilation BP until 3 rd and trimester SVR
40 Pregnancy Goals Prevent severe hypertension Prolong gestation to promote maturity
41 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
42 Pregnancy CHIPS Trial (n=987) Study protocol ~ labetalol 1 st line No ACE inhibitors, ARB, renin blocker, or atenolol
43 CHIPS Trial Tight DBP 85 mmhg Less tight DBP 105 mmhg Adjusted OR Primary ( ) Birth weight <10 percentile Serious maternal complications Severe hypertension* ( ) ( ) ( ) Pre-eclampsia ( )
44 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
45 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
46 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
47 Medication Therapy Beta blockers Primary prevention less effective CV events Stroke Secondary prevention useful
48 Beta blockers Coronary artery disease <130/80 ~ 25% CV events + mortality Post-MI ~ 25% mortality 3 years therapy
49 Beta blockers Coronary artery disease <130/80 ~ 25% CV events + mortality Post-MI ~ 25% mortality 3 years therapy
50 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
51 Hypertenson Key Points ASCVD risk + BP ~ most efficient strategy Moderate dose combination therapy Establish relevant clinical context for medication selection
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