HYPERTENSION GUIDELINES WHERE ARE WE IN 2014 Donald J. DiPette MD FACP Special Assistant to the Provost for Health Affairs Distinguished Health Sciences Professor University of South Carolina University of South Carolina School of Medicine Columbia ACP South Carolina Chapter Scientific Meeting October 25, 2014 3 WHY DO WE NEED GUIDELINES FOR THE TREATMENT OF HYPERTENSION? 1
NHANES: OVERALL POPULATION RESULTS 1988-1994 1999-2000 2007-2008 PREVALENCE(%) 24 29 29 AWARENESS(%) 68 70 81 TREATMENT(%) 54 59 73 CONTROL(%) 27 34 50 JAMA May 2010 ; 303(20) 2043-2050 5 WHERE ARE WE NOW AND NOW DID WE GET HERE? 2
NHLBI System Review and Guideline Development Process Topic Area Identified Evidence Tables Developed; Body of Evidence Summarized Graded Evidence Statements & Recommendations Developed Expert Panel Selected Studies Quality Rated; Data Abstracted External Review of Recommendation Drafts; Revised as Needed Critical Questions &Study Eligibility Criteria Identified Literature Searched; Eligible Studies Identified Guidelines Disseminated & Implemented 9 3
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Relative Risk of Morbidity Compared to Non Hypertensive Population Morbidity ratio (observed/expected) 300 200 100* *Indicates morbidity for non-hypertensive population 83 70 80 90 105 120> Diastolic pressure (mm Hg) Risk of overall morbidity increases with elevation in blood pressure VA Cooperative Study: Morbidity in Patients with a Diastolic Blood Pressure between 115 and 129 mm Hg Placebo Antihypertensive Drug Number in study 70 73 Deaths 4 0 Accelerated hypertension 12 0 Cerebrovascular accident 4 1 Coronary artery disease 2 0 Congestive heart failure 2 0 Renal damage 2 0 Adapted from the VA Cooperative Study: JAMA 202:1028,1967 5
Hypertension Detection and Follow Up Program: Morality by Cause in Mild Hypertension Stepped Care (SC) VS Referred Care (RC) Patients 300 20% Number 200 of Deaths 26% RC = SC = 100 20% 45% 46% Total Deaths HDFP Cooperative Group: JAMA 1979 All Cardiovascular Causes Cerebrovascular Causes Acute MI All Ischemic Heart Disease Framingham Heart Study High normal BP Is Not Benign *CV death, MI, stroke, CHF Adjusted for concomitant CV risk factors Optimal = <120/<80 mmhg Normal = 120 129/80 84 mmhg High normal = 130 139/84 89 mmhg Vasan RS et al. N Engl J Med. 2001;345:1291 1297. JNC 8 Committee: Question 1: When to initiate drug therapy In the general population younger than 60 years, initiate drug treatment at 140 mmhg or 90 mmhg or higher. Ages 30 to 59: Strong Recommendation (A) Ages 18 to 29: Expert Opinion (E) DBP: Strong Recommendation (A) SBP: Expert Opinion (E) 6
GENERAL POPULATION HOT Study: Risk of a Major CV Event Reduced by 30% (DBP) Optimal DBP reduction Percent risk reduction in major CV events* 0-5 -10-15 105 100 95 90 85 80-20 -25-30 *Fatal and nonfatal MI, strokes, all other CV deaths. Hansson L et al. Lancet. 1998;351:1755-1762 7
JNC 8 Committee: Question 2: How low should the treated BP goal be? In the general population younger than 60 years, treat to a goal BP of lower than 140 mmhg or 90 mmhg. Ages: 30 to 59: Strong Recommendation (A) Ages: 18 to 29: Expert Opinion (E) DBP: Strong Recommendation (A) SBP: Expert Opinion (E) 23 PATIENTS WITH HYPERTENSION AND DIABETES Benefits of BP Reduction in HOT: Diabetic Cohort Target DBP (mm Hg) Achieved SBP (mm Hg) Achieved DBP (mm Hg) 90 143.7 85.2 85 141.4 83.2 80 139.7 81.1 Achieved = mean of all BPs from 6 months of follow-up to end of study Major CV Events (per 1000 patient yrs) 50 25 0 85.2 83.2 81.1 Achieved DBP (mm Hg) P = 0.05 for trend Hansson L et al. Lancet. 1998;351:1755-1762. 8
ACCORD STUDY: Intensive Blood Pressure Control in Type 2 Dm NEJM 2010; 362 (17); 1575 ACCORD STUDY: Intensive Blood Pressure Control in Type 2 Dm NEJM 2010; 362 (17); 1575 JNC 8 Committee Question 2 Diabetes: Initial treatment and target BP level Recommendation: In adults 18 years or older, initiate drug treatment to lower BP at a SBP of 140 mmhg or 90 mmhg and treat to lower either to less than 140 mmhg or 90 mmhg. Expert opinion (E) Other opinion: Some evidence to lower DBP to less than 85 mmhg 9
PATIENTS WITH CHRONIC KIDNEY DISEASE MDRD Premise 2 levels of igfr (13 24, 25 55) 2 levels of protein intake (0.6 vs 0.3 g/k/d) 2 levels of blood pressure control (125 mmhg MAP (140/90) vs 92 mmhg MAP(125/75)) Screened: 2507 Randomized: 840 (585 + 255) 10
Estimated mean decline in glomerular filtration rate (GFR) from baseline to selected follow-up times in MDRD Peterson JC, et al Annals of Internal Medicine 1995;123: 754-762 Months 32 MDRD Initial Results Over a mean of 2.2 years of follow-up, the lower BP goal was associated with a reduced rate of GFR loss, compared to the higher BP goal. This benefit was most apparent in patients with more than 1 g proteinuria per day. The study did NOT examine hard endpoints (doubling of serum creatinine, ESRD, or death) 48% of the patients in the lower goal BP group were on an ACEI compared to 26% in the goal BP group 33 11
MDRD Follow-up In the 10 year follow-up, the investigation noted a 32% reduction in ESRD in the lower goal BP group compared to the usual goal BP group. However Limited BP measures during the last 7 years 16-20% greater use of ACEI in the low BP arm Sarnak MJ, et. Al. Ann Intern Med 142:342-351, 2005 34 AASK Randomized 1094 African-Americans to 2 levels of blood pressure: 140/90 mmhg or 125/75 mmhg. Mean measured GFR 45.3 in the conventional and 46.0 ml/min/1.73m2 in the lower BP group Urine protein excretion was 0.61 g/day in men and 0.36 in women Baseline BP was 149/95 mmhg in the conventional and 152/96 mmhg in the lower BP group. Achieved BP was 141/85 in the conventional group and 128/78 mmhg in the lower BP group. Wright J, at. el, Jama.2002;288:2421-2431 35 AASK The lower BP goal did not reduce the clinical composite of 50% reduction of GFR, ESRD, and death compared to the usual BP goal The lack of difference in outcome between BP groups was not altered by randomized treatment (ACEI, BB, or CCB) Wright J, at. el, Jama.2002;288:2421-2431 36 12
Cumulative Incidence of the Composite Primary Outcome, According to Baseline Proteinuria Status. Appel LJ et al. N Engl J Med 2010;363:918-929. 37 JNC 8 Committee Question 2 Chronic Kidney Disease: Initial treatment and target BP level In adults 18 to 69 years with CKD (est GFR 60 or less), initiate drug treatment to lower BP at a SBP of 140 mmhg or DBP of 90 mmhg and treat to goal SBP to lower than 140 mmhg and goal DBP to lower than 90 mmhg. In adults at any age or GFR with albuminuria (30 mg albumin/g creatinine) same goals Expert opinion (E) HYPERTENSION IN THE ELDERLY 13
Systolic Hypertension in the Elderly Program (SHEP Study) Change in Blood Pressure 180 80 170 Placebo (n=2,371) 75 Placebo (n=2,371) 160 70 Active Rx (n=2,365) 150 Active Rx (n=2,365) 140 65 0 1 2 3 4 5 0 1 2 3 4 5 Years Years SHEP Research Group. JAMA. 1991;265:3255-3264. Copyright 1991, American Medical Association. Change in BP (mmhg) Systolic BP Diastolic BP SHEP Cardiovascular Disease Endpoints Relative risk (95% CI) 1.60 Active Therapy vs.. Placebo 1.40 1.20 1.00 0.87 0.80 0.63 0.75 0.68 0.60 0.46 0.40 0.20 Stroke CHD CHF CVD Death CHD=coronary heart disease; CHF=congestive heart failure; CVD=cardiovascular disease SHEP=Systolic Hypertension in the Elderly Program SHEP Research Group. JAMA. 1991;265:3255-3264. HYPERTENSION IN THE VERY ELDERLY TRIAL (HYVET) BP RESULTS NEJM 2008;358:1887 14
HYVET NEJM 2008;358:1887 JNC 8 Committee Question 2: Elderly: Initial treatment and target BP level In adults aged 60 years or older initiate drug treatment to lower BP at a SBP of 150 mmhg or higher or DBP of 90 mmhg or higher and treat to goal SBP to lower than 150 mmhg and goal DBP to lower than 90 mmhg. Strong Recommendation (A) Controversial: Committee members were divided and recent ASH/ISH recommendation maintains goal of 140/90 or less (J Clin HTN). 15
ALLHAT Study Design 33,357 Patients with HTN 55 years or older at least 1 other CHD risk factor Chlorthalidone 12.5-25 mg/d (n = 15255) Amlodipine 2.5-10 mg/d (n = 9048) Lisinopril 10-40 mg/d (n = 9054) Doxazosin 2-8 mg/d Stopped in 2000 Goal BP < 140/90 mm Hg ALLHAT Collaborative Research Group. JAMA. 2002;288:2981-2997. ALLHAT Interim Analysis Doxazosin Arm Discontinued End Chlorthalidone* Doxazosin* Relative P point (n = 15,268) (n = 9067) Risk value CHD 6.30 (0.38) 6.26 (0.30) 1.03 (0.90 1.17).71 Stroke 3.61 (0.22) 4.23 (0.32) 1.19 (1.01 1.40).04 Combined CVD 21.76 (0.49) 25.45 (0.68) 1.25 (1.17 1.33) <.001 CHF 4.45 (0.26) 8.13 (0.43) 2.04 (1.79 2.32) <.001 ALLHAT Collaborative Research Group. JAMA. 2000;283:1967 1975. 16
ALLHAT Results: Primary Outcome* Cumulative CHD Event Rate.2.16.12.08.04 A/C L/C RR (95% CI) 0.98 (0.90-1.07) 0.99 (0.91-1.08) Chlorthalidone Amlodipine Lisinopril p value 0.65 0.81 0 0 1 2 3 4 5 6 7 Years to CHD Event Number at Risk: Chlorthalidone 15,255 14,477 13,820 13,102 11,362 6,340 2,956 209 Amlodipine 9,048 8,576 8,218 7,843 6,824 3,870 1,878 215 Lisinopril 9,054 8,535 8,123 7,711 6,662 3,832 1,770 195 JNC 8 Committee: Question 3: Initial pharmacologic agents In the non black population including those with diabetes, a thiazide type diuretic, reninangiotensin system inhibitor (ACE I or ARB), or calcium channel blocker (CCB) are appropriate initial treatment agents. In the black population including those with diabetes, a thiazide type diuretic or CCB are appropriate initial treatment agents. Moderate recommendation (B) for general population and weak recommendation for blacks with diabetes (C) JNC 8 Committee: Question 3: Initial pharmacologic agents (con t) No specific recommendation on thiazide type although bulk of EBM is with Chlorthalidone. Beta blocker agents not recommended as initial agents due to possible less protection against strokes. Sympatholytics or non CCB vasodilators not recommended, as well. 17
Conclusions New JNC 8 Committee hypertension recommendations are more evidenced based and focused on three critical questions rather than a comprehensive review of the disease state. However, expert opinion is still heavily used. They challenge the current thinking/dogma. The initial BP to start treatment and goal BP levels are higher than previous recommendations, particularly in patients with diabetes and chronic kidney disease, and in the the elderly. Thank you! 18