4/4/17 HYPERTENSION TARGETS: WHAT DO WE DO NOW? SET THE STAGE BP IN CLINICAL TRIALS?

Transcription

1 HYPERTENSION TARGETS: WHAT DO WE DO NOW? MICHAEL LEFEVRE, MD, MSPH PROFESSOR AND VICE CHAIR DEPARTMENT OF FAMILY AND COMMUNITY MEDICINE UNIVERSITY OF MISSOURI 4/4/17 DISCLOSURE: MEMBER OF THE JNC 8 PANEL SET THE STAGE How to take BP in office? JNC 8 ACCORD BP SPRINT HOPE 3 ACP/AAFP Guideline BP IN CLINICAL TRIALS? Mean of 2-3 BP at an office visit Patient was seated, supported 5 minutes of quiet rest Arm cuff measured for fit Not over clothing Arm supported at heart height 1

2 BOTH ACCORD-BP AND SPRINT USED AUTOMATED OFFICE BP MONITORING THE 2015 CANADIAN HYPERTENSION EDUCATION PROGRAM RECOMMENDATIONS FOR BLOOD PRESSURE MEASUREMENT, DIAGNOSIS, ASSESSMENT OF RISK, PREVENTION, AND TREATMENT OF HYPERTENSION CANADIAN JOURNAL OF CARDIOLOGY, , VOLUME 31, ISSUE 5, PAGES HOUR AMBULATORY BP MONITORING IS GOLD STANDARD AUTOMATED OFFICE BLOOD PRESSURE MEASUREMENT IN THE MANAGEMENT OF HYPERTENSION - FOURTH IN SERIES. An article from the e-journal of the ESC Council for Cardiology Practice VOL.13,N MAR

3 AUTOMATED OFFICE BP 5-8 mm Hg lower than routine manual office BP measurement 3

4 JUST SET AND LEAVE 5 minute delay 3 readings averaged WHO WOULD HAVE THOUGHT? It is not your white coat, or your office, it is you 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults REPORT FROM THE PANEL MEMBERS APPOINTED TO THE EIGHTH JOINT NATIONAL COMMITTEE (JNC 8) 4

5 MARCH 2008 NHLBI CONVENED PANELS The JNC 8 will review and synthesize the latest available scientific evidence... QUESTIONS When to initiate drug treatment? How low should you go? How do you get there? RECOMMENDATION In the general population age<60 years, Diastolic threshold/goal of < 90 mm Hg For age years Strong (Grade A) recommendation For age years expert opinion Systolic threshold/goal of <140 mm HG Expert opinion 5

6 CLINICAL TRIALS WITH SBP GOAL AGE < 60 RECOMMENDATION In the general population aged > 60 years Threshold and goal 150/90 (Strong Recommendation Grade A) SYSTOLIC GOAL OF 140? Two trials in general population age > 60 Suggested no benefit from target/threshold lower than 150 Unconvincing 6

7 SYSTOLIC GOAL OF 140? ACCORD BP WHO? Type 2 diabetes mellitus with A1C > 7.5% or more 55 years of age or older with anatomical evidence of a substantial amount of atherosclerosis, albuminuria, left ventricular hypertrophy, or at least two additional risk factors for cardiovascular disease (dyslipidemia, hypertension, smoking, or obesity). Or 40 years of age or older with cardiovascular disease Average age 62.2 WHO? 32% had previous cardiovascular event 7

8 WHAT? Intensive treatment Target systolic BP < 120 Standard treatment Target a systolic BP of 135 to 139 mm Hg The dose was reduced if systolic blood pressure was less than 130 mm Hg on a single visit or less than 135 mm Hg on two consecutive visits BP OUTCOME Systolic BP 14.2 mm Hg lower in intensive group HEALTH OUTCOMES 8

9 HEALTH OUTCOMES Primary outcome composite CVD Intensive 1.87 % per year Standard care 2.09 % per year Hazard ratio = 0.88 ( ) Stroke (the only secondary outcome with a difference) Intensive 0.32 % per year Standard care 0.53 % per year Hazard ratio = 0.59 ( ) JNC 8 RECOMMENDATION In the diabetic population aged > 60 years Threshold and goal 140/90 Expert opinion ORIGINAL ARTICLE A Randomized Trial of Intensive versus Standard Blood-Pressure Control The SPRINT Research Group N Engl J Med 2015; 373: November 26,

10 Age > 50 years Average 67.9 WHO? Systolic blood pressure of 130 to 180 mm Hg WHO? Increased cardiovascular risk Clinical or subclinical cardiovascular disease other than stroke; Chronic kidney disease, (egfr) of 20 to less than 60 ml per minute per 1.73 m2 10-year risk of cardiovascular disease of 15% or greater on the basis of the Framingham risk score; Or age of 75 years or older. WHO? Patients with diabetes mellitus or prior stroke were excluded 10

11 Intensive treatment WHAT? Target systolic BP < 120 Standard treatment Target a systolic BP of 135 to 139 mm Hg The dose was reduced if systolic blood pressure was less than 130 mm Hg on a single visit or less than 135 mm Hg on two consecutive visits 87% of patients in control group had medication reduced HOW? The protocol encouraged, but did not mandate: Thiazide-type diuretics (encouraged as the first-line agent), loop diuretics (for participants with advanced chronic kidney disease), Chlorthalidone was encouraged as the primary thiazide-type diuretic Beta-adrenergic blockers (for those with coronary artery disease). Amlodipine as the preferred calcium-channel blocker OUTCOMES Primary outcome was composite MI or other acute coronary syndromes Stroke Heart failure CV death All-cause mortality 11

12 Systolic Blood Pressure in the Two Treatment Groups over the Course of the Trial. The SPRINT Research Group. N Engl J Med 2015;373: Primary Outcome Ave f/u 3.26 years Goal < 140 Goal < 120 H.R. (95% c.i.) Overall 5.2% 6.8%.75 ( ) Age < % 5.2%.80 ( ) Age > % 10.9%.67 ( ) Primary Outcome The SPRINT Research Group. N Engl J Med 2015;373:

13 All-cause mortality The SPRINT Research Group. N Engl J Med 2015;373: SERIOUS ADVERSE EVENT Fatal or life threatening Clinically significant or persistent disability Required or prolonged a hospitalization Judged by investigator to represent a clinically significant hazard or harm that might require intervention to prevent one of the above Serious Adverse Events, Conditions of Interest, and Monitored Clinical Events. The SPRINT Research Group. N Engl J Med 2015;373:

14 Original Investigation June 28, 2016 Intensive vs Standard Blood Pressure Control and Cardiovascular Disease Outcomes in Adults Aged 75 Years A Randomized Clinical Trial JAMA. 2016;315(24): AGE > 75 EXCLUSIONS Dementia Predicted survival of < 3 years Unintentional weight loss past 6 months SBP < 110 mm Hg after 1 min standing Nursing home Too many BP meds BASELINE MEDICATIONS AND ELIGIBILITY (SBP MM HG) meds 3 meds 2 meds 0-1 meds eligible not eligible 14

15 OUTCOMES IN AGE > 75 YRS Primary outcome Intensive Rx 102/ % Standard Rx 148/ % Hazard ratio 0.66 ( ) Risk difference 3.5% Serious adverse events similar Orthostatic hypotension (2.4% vs 1.4%), syncope (3.0% vs 2.4%), AKI or renal failure (5.5% vs 4.0%) OUTCOMES IN AGE > 75 YRS All cause mortality Intensive Rx 73/ % Standard Rx 107/ % Hazard ratio 0.67 ( ) Risk difference 2.6% Note: average age year population mortality rate at age 80 is 30% 15

16 EVIDENCE SUMMARY LOWER TARGET Inconsistent trial results, with imprecise estimates of benefit Evidence was most consistent for a reduction in stroke, with an absolute risk reduction of 0.49% and a number needed to treat (NNT) of 204. The results for mortality were nonsignificant For cardiac events borderline nonsignificant, with an NNT of 106 ACP/AAFP panel recommendations 1. Initiate treatment in adults aged 60 years or older with systolic blood pressure persistently at or above 150 mm Hg to achieve a target systolic blood pressure of less than 150 mm Hg to reduce the risk for mortality, stroke, and cardiac events. Strong recommendation, high-quality evidence. 2. Consider initiating or intensifying pharmacologic treatment in adults aged 60 years or older with a history of stroke or transient ischemic attack to achieve a target systolic blood pressure of less than 140 mm Hg to reduce the risk for recurrent stroke. Weak recommendation, moderate-quality evidence. 3. Consider initiating or intensifying pharmacologic treatment in some adults aged 60 years or older at high cardiovascular risk, based on individualized assessment, to achieve a target systolic blood pressure of less than 140 mm Hg to reduce the risk for stroke or cardiac events. Weak recommendation, low-quality evidence. For each recommendation, shared decision making was emphasized. EVIDENCE REVIEW 16

17 EVIDENCE REVIEW EVIDENCE REVIEW Original Article Blood-Pressure Lowering in Intermediate-Risk Persons without Cardiovascular Disease N Engl J Med Volume 374(21): May 26,

18 WHO? Men age 55 years and older; women age 65 years and older At least one: Elevated waist-hip ratio Low HDL Current/recent smoking Dysglycemia Family hx premature CAD Mild renal dysfunction WHO? Average age /- 6.4 Average baseline SBP / Average baseline DBP /- 9.4 WHAT? RCT 2x2 factorial design Intervention 16 mg candesartan 12.5 mg HCTZ Office BP, average of 2 readings after 5 minutes rest 18

19 Systolic Blood Pressure over the Course of the Trial, According to Trial Group. Lonn EM et al. N Engl J Med 2016;374: OUTCOMES Primary outcome was composite MI or other acute coronary syndromes Stroke CV death Secondary outcome also included Heart failure Revascularization Cumulative Incidence of Major Cardiovascular Events, According to Trial Group. Lonn EM et al. N Engl J Med 2016;374:

20 QUESTIONS? 20