Hypertension in the Era of ACC/AHA: Practice Changing Evidence and Recommendations

Transcription

1 Hypertension in the Era of ACC/AHA: Practice Changing Evidence and Recommendations Gerald W. Smetana, M.D., MACP Division of General Medicine Beth Israel Deaconess Medical Center Professor of Medicine Harvard Medical School

2 Goals ACC/AHA 2017: new recommendations and controversies >130/80 is now hypertension USPSTF: How to diagnose hypertension Importance of white coat hypertension Chlorthalidone preferred over HCTZ Mixed results for ARBs Risks of alpha-blockers and beta-blockers Goal bp <130/80 for most patients Approach to resistant hypertension Expanding role for spironolactone and labetalol

3 All Drugs that Lower Blood Pressure Do Not Equally Reduce Cardiovascular Risk >130/80 is Now Hypertension

4 Case: Mr. Dash 53 year-old man Resident of the MFA Elevated cholesterol PAD by exam 15 year history of hypertension On HCTZ, losartan Office bp 138/88 He wants to know: Is this best regimen for me?

5 NHANES 2014: Prevalence of Hypertension ( >140/90) in U.S.

6 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/ APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults American College of Cardiology Foundation and American Heart Association, Inc. E-pub ahead of Press, November 2017

7 New BP Classifications SBP And / Or DBP Normal < 120 and < 80 Elevated and < 80 Stage 1 Hypertension Stage 2 Hypertension or or 90 ACC/AHA 2017

8 Prevalence of Hypertension Based on New and Old BP Thresholds SBP/DBP 130/80 mm Hg or Self-Reported Antihypertensive Medication SBP/DBP 140/90 mm Hg or Self- Reported Antihypertensive Medication Overall, crude 46% 32% Men (n=4717) Women (n=4906) Men (n=4717) Women (n=4906) Overall, age-sex adjusted 48% 43% 31% 32% Age group, y % 19% 11% 10% % 44% 33% 27% % 63% 53% 52% % 75% 64% 63% % 85% 71% 78% Race-ethnicity Non-Hispanic White 47% 41% 31% 30% Non-Hispanic Black 59% 56% 42% 46% Non-Hispanic Asian 45% 36% 29% 27% Hispanic 44% 42% 27% 32%

9 White Coat Hypertension: A Pre-Hypertensive State 2015 persons Normotensive (52%) Hypertensive (23%) White coat (25%) Divided white coat into true (all home reads normal) and partial (at least one home bp elevated) 16 years of followup 50% 45% 40% 35% 30% 25% 20% 15% 10% 5% 0% Incidence of New Onset Hypertension Over 16 years Normotensive True White Coat Partial White Coat Hypertension 2013;62:168

10 Recommendation Statement from USPSTF on Screening for HTN Ann Intern Med November 17, Recommend screening for high blood pressure in adults 18 years. Screen yearly beginning at age 40 (Grade A) 2. Recommend obtaining measurements outside of the clinical setting before starting treatment. Ambulatory 24-hour measurements preferred. Casual home monitoring acceptable (Grade A)

11 Equivalent Bp Values by Office, 24- Hour ABPM, and Home Monitoring (HBPM) Office HBPM Daytime ABPM Nighttime ABPM 24-Hour ABPM 120/80 120/80 120/80 100/65 115/75 Stage 1 130/80 130/80 130/80 110/65 125/75 140/90 135/85 135/85 120/70 130/80 160/ /90 140/90 140/85 145/90 ACC/AHA 2017

12 BP Targets: Guidelines are Out of Date 2013 JNC-8 Target bp 140/90, 150/90 if < 60 y.o American Society of Hypertension Bp target 150/90 only if > 80 y.o European Society of Hypertension Discretion for 150/90 or 140/90 target if Canadian Hypertension Education Program Target bp 150/90 if > 80 y.o.

13 No Benefit in Composite Outcome with Lower Target BP in Diabetic Patients in ACCORD N= 4733 Target sbp 120 vs 140 ADA / JNC-8 Target bp < 140/90 NEJM 2010;362:1575

14 SPRINT Study of Optimal BP Targets: Is this a Game Changer? Age 50 Systolic bp Elevated CV risk: Clinical or subclinical CV disease CKD with egfr Framingham 10-year risk 15% Age > 75 years Exclusions: Diabetes Prior stroke Randomly assigned to: Sbp 140 mm Hg Sbp 120 mm Hg Drug choice left to clinician Median follow up 3.3 years (stopped early) N = 9361 patients NEJM 2015;373:2103

15 Systolic Blood Pressure in the Two Treatment Groups over the Course of the Trial

16 Lower Target BP Reduced Composite Outcome and Mortality

17 Other Findings Non-significant reduction in composite outcome for: 1. Women 2. Previous CKD 3. Black/Hispanic 4. Previous CV disease Adverse events more common at systolic bp Hypotension 2. Syncope 3. AKI 4. Hyponatremia 5. Hypokalemia Average 2.7 drugs in intensive group

18 Do ACCORD and SPRINT Actually Differ? NEJM2015;373:2175

19 ACP 2017 Guidelines on Rx of Hypertension in Adults > 60 Years Old 1. Initiate treatment if systolic bp persistently 150 mm Hg to achieve a target systolic bp of < 150 mm Hg 2. Initiate or intensify pharmacologic treatment if a history of stroke or TIA to achieve a target systolic bp of < 140 mm Hg 3. Initiate or intensify pharmacologic treatment in some adults at high CV risk, based on individualized assessment, to achieve a target systolic bp of < 140 mm Hg Ann Intern Med 2017;166:430

20 ACC/AHA 2017: When to Initiate Medication and to What Goal? Patients Secondary Prevention BP Threshold to Initiate Rx Target BP for Rx Clinical CVD 130/80 < 130/80 Primary Prevention 10 year CVD risk of 10% 10-year CVD risk < 10% 130/80 <130/80 140/90 <130/80 reasonable

21 Secondary (Identifiable) Causes of Hypertension Cushing s syndrome Renal artery stenosis Primary aldosteronism Pheochromocytoma Chronic kidney disease Coarctation of the aorta Thyroid or parathyroid disease Drug or alcohol induced Obstructive sleep apnea

22 When to Screen for Primary Aldosteronism? Hypertension and spontaneous hypokalemia Hypokalemia induced by low dose diuretics Resistant hypertension (suboptimally controlled on at least a three-drug program that includes a diuretic) HTN with adrenal incidentaloma Family h/o early onset HTN Stroke at young age (<40 y.o.) Screen with plasma aldosterone concentration / plasma renin ratio PAC/PRA > 20 indicates probable primary aldosteronism Rx: Either spironolactone or subspecialty referral ACC/AHA 2017 & Endocrine Society 2017

23 Expanded Laboratory Test Recommendations for Primary Hypertension Basic testing Optional testing Fasting blood glucose* Complete blood count Lipid profile Serum creatinine with egfr* Serum sodium, potassium, calcium* Thyroid-stimulating hormone Urinalysis Electrocardiogram Echocardiogram Uric acid Urinary albumin to creatinine ratio *May be included in a comprehensive metabolic panel. egfr indicates estimated glomerular filtration rate.

24 ACC/AHA 2017: Proven (Class Ia) Lifestyle Modifications Prevent CV Disease 1. DASH/USDA type diet: vegetables, fruits, whole grains, low fat dairy, poultry, fish, legumes, vegetable oils, nuts. Limit sweets, sugar-sweetened beverages, and red meat 2. Weight loss 3. Lower sodium intake 4. High potassium diet (if no CKD or drug contraindication) 5. Moderate to vigorous aerobic physical activity x 40 minutes, 3-4 times per week 6. If drink alcohol, moderate intake

25 Medications Man has an inborn craving for medicine The desire to take medicine is one feature which distinguishes man, the animal, from his fellow creatures Even in minor ailments, which would yield to dieting or to simple home remedies, the doctor s visit is not thought to be complete without the prescription. William Osler 1895

26 TRANSCEND: Telmisartan Does Not Reduce CV Endpoints if Intolerant to ACEi 5926 high risk patients Existing CV disease or diabetes End organ disease Intolerant to ACEi Key exclusions: CHF Sbp > 160 CKD Randomized to telmisartan 80 mg or placebo Endpoint = CV Death + MI + Stroke + CHF Admit HR 0.92, p = 0.22 Placebo Telmisartan Lancet 2009;372:1174

27 NAVIGATOR: Valsartan Does Not Reduce CV Risk For Patients with Glucose Intolerance N=9306 Impaired fasting glucose Established CV disease or CV risk factors 77% were hypertensive Valsartan mg qd vs placebo NEJM 2010;362:1477

28 HOPE 3: No Hope for ARB s: Another Negative Trial N = 12,705 Primary prevention Men > 55 yo, Women > 65 yo At least one CV risk factor Candesartan 16 mg/hctz 12.5 vs. placebo Mean bp decrease 6.0/3.0 mm Hg Outcome: Death from CV disease, MI, stroke, arrest, revascularization, CHF NEJM 2016;374:2009

29 Criticisms of HOPE 3 Results reported as no benefit of Rx for HTN in intermediate risk patients Baseline bp 138/82 mm Hg (SD 15/9) Only 1/3 of patients had HTN at baseline Significant reductions in outcomes in the tertile with highest baseline bp Used submaximal fixed low dose for both HCTZ and candesartan (1/2 of max dose) Selected HCTZ rather than chlorthalidone This was another negative ARB trial

30 ACEi + ARB. More is Not Always Better: No Difference in Composite CV Endpoint ONTARGET Trial 25,620 patients 55 y.o. CAD PVD CVA or TIA DM with end organ damage NEJM 2008;358:1547

31 Combination Therapy: More Adverse Events Despite No Benefit 3 Ramipril Telmisartan Both RR versus Ramipril Hypotensive Sx Syncope Renal Impairment = p <0.05

32 Aliskiren Increases Morbidity in Diabetic Patients with Renal Disease Direct renin inhibitor ALTITUDE Trial: Type 2 diabetes plus renal impairment (proteinuria or CKD) All patients on ACEi or ARB Randomized to addition of aliskiren or placebo Composite outcome of mortality, CV, and renal outcome Terminated due to lack of efficacy at 27 months Higher rates or renal impairment, hypotension, and hyperkalemia with aliskiren Marginal increase in stroke and death FDA: Contraindicated as part of dual Rx with ACEi or ARB NEJM 2012;367:2204

33 Meta-Analysis: Adverse Events Common with Aliskiren Hyperkalemia AKI Hypotension Diabetes Vasc Research 2017;14:400

34 Renin/Angiotensin/Aldosterone Suppression: Conclusions ACEi reduce CV risk to same degree as diuretics ACEi are appropriate first-line agents ARB s comparable to ACEi in ONTARGET ARB s are not effective when ACEi intolerant or if glucose intolerance Pending further study, would move ARBs to second line status This is controversial. ACC/AHA endorses ARBs Do not use aliskiren (FDA restricts use only in dual Rx)

35 ALLHAT JAMA 2002;288: Hypertensive patients 55 yrs with at least one other CV risk factor Consent / Randomize (42,418) Amlodipine Chlorthalidone Doxazosin Lisinopril Eligible for lipidlowering Not eligible for lipid-lowering Consent / Randomize (10,355) Pravastatin Usual care Follow for CHD until death or end of study (mean 4.9 years)

36 Chlorthalidone vs. Amlodipine: Lower CHF Rates 20% All Cause Mortality RR = 0.96 p = % Heart Failure RR = 1.38 p < % 16.8% 15% 10% 10.2% 10% 7.7% 5% 5% 0% 0% Chlorthalidone Amlodipine Chlorthalidone Amlodipine

37 Chlorthalidone vs Lisinopril: Lower CHF and Stroke Rates 20% All Cause Mortality RR = 1.00 p = % Heart Failure RR = 1.19 p < % Stroke RR = 1.15 p = % 17.2% 8% 15% 10% 7.7% 8.7% 6% 5.6% 6.3% 10% 4% 5% 5% 2% 0% 0% 0% Chlorthalidone Lisinopril Chlorthalidone Lisinopril Chlorthalidone Lisinopril

38 Meta-Analysis: Fewer CV Events for Chlorthalidone than HCTZ Systematic review Studies include chlorthalidone or HCTZ in one arm N =9 studies Mean bp reduction greater for CTD than HCTZ Lower CV rates for CTD even after controlling for bp Outcome for Chlorthalidone when Compared to HCTZ Outcome Drug adjusted RR Mortality 0.94 Stroke 0.77 Total CV events CHF 0.77* Bp adjusted RR 0.79* 0.82* Hypertension 2012;59:1110

39 Which Diuretic to Choose? AHA/ACC: one of 4 choices for initial Rx One of two choices for African American patients Chlorthalidone is twice as potent as HCTZ Longer half life than HCTZ of 24 hours More effective at lowering night time bp Most positive diuretic trials have used chlorthalidone Chlorthalidone should now become our preferred diuretic for Rx of hypertension Start at 12.5 mg daily Increased hypokalemia check K + in 2 weeks

40 ACCOMPLISH: ACEi/CCB vs. ACEi/HCTZ CCB Based Regimen is Superior Cumulative event rate ACEI / HCTZ CCB / ACEI 20% Risk Reduction p = Time to 1 st CV morbidity/mortality (days) NEJM 2008;359:2417

41 Calcium Channel Blockers: Recommendations Some conflicting data Higher CHF rates in ALLHAT ACCOMPLISH strongest data yet May be superior as part of combination Rx Good data for systolic HTN in elderly I am now moving CCBs up to a 1 st line therapy

42 Doxazosin Inferior to Chlorthalidone ALLHAT Cumulative Primary Event Rate doxazosin chlorthalidone Years of Follow-up C: 15,268 D: 9,067 Rel Risk 1.25 p < ,990 7,382 95% CI ,443 5,285 4,827 2,654 2,010 1,083 JAMA 2000;283:1967

43 Cochrane 2017: β Blockers Are No More Effective than Placebo for Total Mortality Cochrane Database 2017: Issue 1

44 Cochrane: β Blockers Reduce Stroke Risk Less than Other Antihypertensive Drugs

45 Beta-Blockers: Recommendations Do not use as first line or second line treatment for hypertension Consider if three or more drugs required as part of multi-drug regimen for patients with drug intolerances and limited options Probably a class effect but most negative trials are for atenolol These recommendations apply only to primary prevention

46 Cochrane Review: Efficacy of 1 st Line Treatments for Hypertension Class Mortality Stroke CHD CV Events Thiazides Beta blockers CCB ACEi Cochrane Library 2009, Issue 3

47 Significant Benefits: Only Thiazides and ACEi Reduce All CV Endpoints Class Mortality Stroke CHD CV Events Thiazides Beta blockers CCB ACEi Cochrane Library 2009, Issue 3

48 Drug Selection if Comorbidities Comorbid Condition Preferred First Line Drugs Stable CAD HFpEF CKD Stage III or albuminuria > 300 mg/d Prior stroke Diabetes Beta blockers, ACEi, ARB based on compelling indications (prior MI, etc) ACEi or ARB, beta blockers. Diuretics if volume overloaded ACEi. ARB if ACEi not tolerated Thiazide, ACEi, ARB, or combination ACEi/thiazide Any first line med. ACEi or ARB if albuminuria ACC/AHA 2017

49 One Third of Patients with Resistant Hypertension Have White Coat Hypertension Resistant HTN =Uncontrolled despite 3 drugs including diuretic Hypertension 2011;57:898

50 Resistant Hypertension: Treatment Strategies Effective combinations ACEi/diuretic ACEi/CCB Change HCTZ to chlorthalidone Add spironolactone Add furosemide if CKD Third line strategies for severe essential hypertension Labetalol Carvedilol Clonidine Dual CCB s Hydralazine Minoxidil

51 RCT: Spironolactone Superior to Ramipril in Resistant Hypertension 167 patients Resistant hypertension Randomly assigned to addition of spironolactone or ramipril Endpoint bp changes at 12 weeks Spironolactone Ramipril J Hypertens 2012;30: Decrease in SBP Decrease in DBP

52 RCT: Spironolactone Superior to Bisoprolol and Doxazocin for Resistant Hypertension N= 335 Resistant bp despite max tolerated of 3 drugs (ACEi or ARB, CCB, and Thiazide) Rotated through each of 3 drugs as add-on Rx over 6 and 12 weeks Note: 2% incidence of K + > 6.0 Lancet: 2015;386:2059

53 Average Wholesale Price for 1 Month Supply Class Drug Monthly Cost 4$ Option Diuretics Chlorthalidone12.5 mg $10 X (HCTZ) β-blockers Atenolol 25 mg $12 X CCB Nifedipine 30 mg $28 Amlodipine 5 mg $2 ACEi Lisinopril 10 mg $2 X Enalapril 10 mg $14 X ARB Valsartan 80 mg $14 Losartan 50 mg $5 Source: Medical Letter March 2017, Rx PriceQuotes.com

54 Summary of Evidence Drug class Evidence for CV risk reduction Compelling indications Diuretics Yes Systolic HTN elderly, CHF ACEi Yes LV dysfunction, post MI, CKD, albuminuria CCB Yes Systolic HTN elderly ARB Mixed LV dysfunction Diabetes with albuminuria Beta-blockers Inferior Post MI LV dysfunction Alpha blockers Inferior None Renin inhibitor Inferior None

55 Mr. Dash: What Should We Recommend? Change HCTZ to chlorthalidone Change losartan to ACEi or CCB Bp target < 130/80 (SPRINT eligible, > 10% CV risk per AHA/ACC)

56 What is New that Should Change Our Practice? >130/80 is now Stage I hypertension Confirm all elevated office bp values with home measurement before treatment. Diagnosis thresholds differ for home readings Don t use beta blockers or alpha blockers Don t use ACEi and ARB together ARBs are possibly inferior Goal for drug Rx < 130/80 for most patients Consider white coat hypertension if apparently resistant hypertension Spironolactone and labetalol for resistant hypertension

57 ACC/AHA: Summary of BP Thresholds to Begin Rx and Goals of Pharmacological Therapy Clinical Condition(s) BP Threshold, mm Hg BP Goal, mm Hg General Clinical CVD or 10-year ASCVD risk 10% 130/80 <130/80 No clinical CVD and 10-year ASCVD risk <10% 140/90 <130/80 Older persons ( 65 years of age; noninstitutionalized, ambulatory, community-living adults) 130 (SBP) <130 (SBP) Specific comorbidities Diabetes mellitus 130/80 <130/80 Chronic kidney disease 130/80 <130/80 Chronic kidney disease after renal transplantation 130/80 <130/80 Heart failure 130/80 <130/80 Stable ischemic heart disease 130/80 <130/80 Secondary stroke prevention 140/90 <130/80 Secondary stroke prevention (lacunar) 130/80 <130/80 Peripheral arterial disease 130/80 <130/80

58 Blood Pressure (BP) Thresholds and Recommendations for Treatment and Follow-Up BP thresholds and recommendations for treatment and follow-up Normal BP (BP <120/80 mm Hg) Elevated BP (BP /<80 mm Hg) Stage 1 hypertension (BP /80-89 mm Hg) Stage 2 hypertension (BP 140/90 mm Hg) Promote optimal lifestyle habits Nonpharmacologic therapy (Class I) Clinical ASCVD or estimated 10-y CVD risk 10%* No Yes Reassess in 1 y (Class IIa) Reassess in 3 6 mo (Class I) Nonpharmacologic therapy (Class I) Nonpharmacologic therapy and BP-lowering medication (Class I) Nonpharmacologic therapy and BP-lowering medication (Class I)

59 All Drugs that Lower Blood Pressure Do Not Equally Reduce Cardiovascular Risk >130/80 is Now Hypertension