Hypertension Guidelines 2016

Transcription

1 Hypertension Guidelines 6 Michael A. Weber, MD Division of Cardiovascular Medicine State University of New York Downstate Medical Center Speaker Disclosures I disclose that I am a Consultant for: Ablative Solutions, Boston Scientific, Eli Lilly, Medtronic, Novartis, ReCor What Are the Key Recommendations by a Hypertension Practice Guideline? The threshold blood pressure values that define hypertension and set treatment targets The optimal choice of drugs for reducing blood pressure and maximizing cardiovascular, stroke and renal protection

2 What is the appropriate blood pressure target? To adequately define hypertension, it is necessary to establish the evidence-based blood pressure threshold that should be achieved by treatment. Should it be < mmhg, or < mmhg, or <3 mmhg, or < mmhg? CHD Rates by SBP, DBP and Age IHD Mortality (Floating Absolute Risk and 9% CI) A: Systolic Blood Pressure Age at risk: IHD Mortality (Floating Absolute Risk and 9% CI) B: Diastolic Blood Pressure Age at risk: Usual Systolic Blood Pressure (mm Hg) 7 9 Usual Diastolic Blood Pressure (mm Hg) Adapted from Lewington et al. Lancet. ; 36: V7 Systolic Hypertension in the Elderly Program (SHEP) Multicenter, randomized, double-blind, placebo-controlled, patients 6 years, systolic BPs 6 mm Hg & diastolic BPs <9 mm Hg, using.- mg chlorthalidone + other drugs if needed (Starting SBP: 7 mm Hg; achieved SBP: Placebo mm Hg, active treatment 3 mm Hg) Cumulative fatal and nonfatal stroke rate per participants 6 SHEP Cooperative Research Group. JAMA. 99;6:3-36. Placebo (n=37) 36 6 Months 36% Active treatment (n=36) 7

3 James PA. et al. JAMA. 3 Dec. doi:./jama.3.7. [Epub ahead of print]. Authors of JNC Panel: Recommendation In the general population aged 6 years or older, initiate pharmacologic treatment to lower BP at systolic blood pressure (SBP) of mm Hg or higher or diastolic blood pressure (DBP) of 9 mm Hg or higher and treat to a goal SBP lower than mm Hg and goal DBP lower than 9 mm Hg. Strong Recommendation Grade A Note: This was one of only two of the nine recommendations of the panelists that claimed to be Strong and Grade A HYVET: % Reduced Mortality With Active Treatment in Patients Aged or more Active (SBP: 3 mm Hg) versus placebo (SBP: mm Hg) in patients aged or older 3 No. of events per patients Placebo group Active treatment group No. at risk Placebo group Active-treatment group 3 Follow-up (yr) Beckett NS et al. N Engl J Med. ;3:

4 Effective BP Control (SBP < mmhg) Reduces Cardiovascular Risk (VALUE Trial) HR (9% CI) of CV events in patients being followed up to 6 years Fatal and non-fatal cardiac events Fatal and non-fatal stroke All-cause death Myocardial infarction Heart failure hospitalizations.7 (.67.3). (.6.6).79 (.7.).6 (.73.).6 (..7).6... SBP controlled at 6 months (n=,7) SBP not controlled at 6 months (n=,9) * Pooled analysis of patients enrolled in the VALUE trial; blood pressure control defined as SBP < mmhg Statistically significant difference (p<.) vs SBP not controlled at 6 months BP=blood pressure; CI=confidence interval; CV=cardiovascular; HR=hazard ratio; SBP=systolic blood pressure; VALUE=Valsartan Antihypertensive Long-term Use Evaluation Weber MA, et al. Lancet;363:9-. ACCORD: Mean Systolic Pressures in Over Time (Patients with Diabetes) Intensive Standard SBP (mm Hg) 3 Average : 33. Standard vs 9.3 Intensive, delta =. N = post-randomization Mean number of medications Intensive: Standard: Number of patients Intensive:,7,7,973,79, 6 6 Standard:,,36,77,6, 3 Data shown are mean ± 9% CI. ACCORD study group. N Engl J Med. ;36:7. ACCORD: Primary Outcome and Total Stroke Primary Outcome (Nonfatal MI, nonfatal stroke or CVD death) HR =.9 9% CI (.73-.7) HR =.9 9% CI (.39-.9) Nonfatal Stroke Patients with events (%) NNT for years = 9 Intensive Standard post-randomization post-randomization ACCORD study group. N Engl J Med. ;36:7.

5 SPRINT Research Question Examine effect of more intensive high blood pressure treatment than is currently recommended Randomized Controlled Trial Target Systolic BP Intensive Treatment Goal SBP < mm Hg Standard Treatment Goal SBP < mm Hg SPRINT design details available at: ClinicalTrials.gov (NCT66) AmbrosiusWT et al. Clin. Trials. ;:3-6. Systolic BP During Follow-up Year Mean SBP 36. mm Hg Standard Average SBP (During Follow-up) Standard: 3.6 mm Hg Mean SBP. mm Hg Intensive Intensive:. mm Hg Average number of antihypertensive medications Number of participants SPRINT Primary Outcome and its Components Event Rates and Hazard Ratios Intensive Standard No. of Events Rate, %/year No. of Events Rate, %/year HR (9% CI) P value Primary Outcome (.6,.9) <. All MI (.6,.9).9 Non-MI ACS.7.7.(.6,.).99 All Stroke (.63,.). All HF (.,.). CVD Death (.3,.).

6 Renal Disease Outcomes Intensive Standard Events %/yr Events %/yr HR (9% CI) P Participants with CKD at Baseline Primary CKD outcome (.,.7).76 % reduction in egfr * (.36,.7).7 Dialysis (.9,.).7 Kidney transplant Secondary CKD Outcome Incident albuminuria** (.,.7). Participantswithout CKD at Baseline Secondary CKD outcomes 3% reduction in egfr* (.,.) <. Incident albuminuria**. 3.. (.63,.). *Confirmed on a second occasion 9 days apart **Doubling of urinary albumin/creatinine ratio from < to > mg/g Major Outcomes by Achieved Systolic Blood Pressure Category in ACCOMPLISH Increased Serum Creatinine (>%) 7 p-values versus > Events per, Patient Patients with diabetes Patients without diabetes p-values versus > to < to <3 3 to < > Achieved Systolic Blood Pressure (mmhg) How to Interpret SPRINT Could result be due to more intensive treatment rather than more intensive BP control? Mean systolic BP in Intensive group was. mmhg, with >% of patients above mmhg So, despite the original intention to test < mmhg, do these findings better support a target of < 3 mmhg? Measurement of BP by rigorous use of automated device in SPRINT (to minimize white coat effect) such that SPRINT readings might have been - mmhg lower than typical practice readings, again suggesting a <3 mmhg rather than < mmhg target 6

7 Clinical Trials Where Different Drug Treatments Produced Differing Outcomes Independent of Blood Pressure LIFE ASCOT ACCOMPLISH ALLHAT In SPRINT the Intensive Group had significantly greater use of ACEi, ARBs, CCBs, thiazides, spironolactone Characteristic Benazepril + Amlodipine Benazepril + HCTZ Hazard Ratio (9% CI) p-value Number of Patients,66,93 Mean BP after Titration 3/73 mmhg 33/73 mmhg Primary endpoint (.) 6(7.).73 (.7 -.9). CV death + MI + stroke Fatal and non-fatal MI (.) 6 (3.).7 (.9.).9 Stroke (.) 63 (.).76 (..).3 CV death (.) 6 (.6).7 (..).37 Hospitalized HF 6 (.) 9 (.3).9 (..).679 All-cause death 9 (.) 3 (.).77 (.9.). SPRINT Endpoint* 6 (7.3) 3 (9.3).77 (.6.9). ACCOMPLISH: Endpoints for the Non-diabetes Cohort Values are absolute numbers (percentages). Abbreviations: HCTZ=hydrochlorothiazide; MI=myocardial infarction; UA=unstable angina; CV=cardiovascular; HF=heart failure *Composite of MI, other acute coronary syndromes, stroke, heart failure or CV death, added to this Table following publication of SPRINT Trial Adapted from: Weber et al. JACC ;6:77- Therapy Most evidence now supports 3 drug types: the RAS blockers (ACE inhibitors or ARBs); calcium channel blockers; and diuretics. Evidence for beta blockers weaker, except if HF, post-mi, angina, AF Chlorthalidone & indapamide seen as alternatives to HCTZ; growing interest in spironolactone for difficult-to-control hypertension Combination treatment is required in >% of patients and can be used to start therapy 7

8 Proportion of patients (%) LIFE Trial: Losartan vs Atenolol as Initial Therapy Cardiovascular Mortality Atenolol Losartan Adjusted risk reduction:.%, P=.6 Unadjusted risk reduction: 3.3%, P= Stroke (Fatal and Nonfatal) Adjusted risk reduction:.9%, P=. Unadjusted risk reduction:.%, P=.6 No. at risk Losartan Atenolol Reprinted from The Lancet, 39(93), Dahlöf B et al, Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol, 99-3,, with permission from Elsevier. Dahlöf B et al. Lancet ; 39: Chlorthalidone (CLD) Had Positive Effects on Cardiovascular Outcomes in Landmark Studies Clinical study HDFP MRFIT,3 SHEP ALLHAT Population studied and duration of study Comparators Significant findings,9 adults with HTN Over years,66 high risk males with HTN Over. years,736 adults >6 years of age with ISH Over years 33,37 high risk adults with HTN Over.9 years CLD Usual care CLD HCTZ Usual care CLD Placebo CLD Amlodipine Lisinopril CLD reduced mortality by 7% vs usual care CLD reduced mortality rate vs HCTZ CLD lowered risk for CV events by % vs HCTZ CLD lowered risk for CVD by 3% vs placebo CLD was similar to amlodipine and lisinopril in prevention of fatal and nonfatal coronary events ALLHAT=Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial; CLD=chlortalidone; CVD=cardiovascular disease; CV=cardiovascular; HCTZ=hydrochlorothiazde; HDFP=Hypertension Detection and Follow-up Program; HTN=hypertension; ISH=isolated systolic hypertension; MRFIT=Multiple Risk Factor Intervention Trial; SHEP=Systolic Hypertension in the Elderly Program. Hypertension Detection and Follow-up Program Cooperative Group. JAMA. 979;:6-7.. Multiple Risk Factor Intervention Trial Research Group. Circulation. 99;: Dorsch MP, et al. Hypertension. ;: SHEP Cooperative Research Group. JAMA. 99;6:3-6. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. JAMA. ;:9-97. ASCOT: Primary and Secondary End Points Amlodipine/Perindopril vs Atenolol/Bendroflumethiazide End point All-cause mortality Primary end point: nonfatal MI and fatal CHD Total coronary end point: primary end point + new-onset angina + fatal and nonfatal heart failure Fatal and nonfatal stroke All CV events and revascularization procedures CV mortality Hazard Ratio P Value....7 <..7.. Favors Amlodipine/Perindopril Favors Atenolol/Bendroflumethiazide ASCOT = Anglo-Scandinavian Cardiac Outcomes Trial; MI = myocardial infarction; CHD = cardiovascular heart disease; CV = cardiovascular. Sever PS, Dahlöf B. American College of Cardiology Scientific Sessions; March 6-9, ; Orlando, FL.

9 Uses of Home BP. Growing importance due to ease of measurement with electronic devices. Confirm diagnosis of hypertension ---- ASH/AHA recommend home BP x day for days; if average of all readings is >/9 mmhg, this confirms diagnosis 3. Assess effects of treatment, particularly early morning BP. Improves compliance with treatment NOTE: Ambulatory BP monitoring recommended to enhance diagnosis of hypertension, but still remains unavailable or expensive in most settings Headlines for 6 Likely that mmhg will remain threshold for many patients (including those with diabetes), but mmhg, or more likely, 3 mmhg will have a growing role Defining thresholds for important groups of patients non-high risk, young adults still not achieved Drug choice/selection of combinations may be critical in maximizing CV protection RAS blockers/ccbs/thiazides are core; beta blockers, unless indicated, are less proven; chlorthalidone & spironolactone getting attention Growing focus on home BPs, even ABPM 9