Evolving Concepts on Hypertension: Implications of Three Guidelines (JNC 8 Panel, ESH/ESC, NICE/BSH) Sidney C. Smith, Jr. MD, FACC, FAHA, FESC Professor of Medicine/Cardiology University of North Carolina at Chapel Hill Nothing to Disclose
Institute of Medicine Report: Quality Chasm In its current form, habits, and environment, American health care is incapable of providing the public with the quality health care it expects and deserves. Design Rule 5: Current: Decision making is based on training and experience. New: Decision making is based on evidence. Patients should receive care based on the best available scientific knowledge. Care should not vary illogically form clinician to clinician or from place to place. Institute of Medicine, Crossing the Quality Chasm: A New Health System for the Twenty-first Century. Washington: National Academy Press, 2001
Why RCTs? Durability of Class I Cardiology Guideline Recommendations 1) 91% retained if Level of Evidence A: Multiple RCTs or meta-analyses 2) 81% if Level of Evidence B: Single RCT or non-randomized studies 3) 74% if Level of Evidence C: Consensus Opinion, Case Studies or Standard of Care Most important Level of Evidence A is unlikely to be downgraded, reversed, or omitted unlike lower forms of evidence. JAMA 2014:311 (20);2092-2100. RCT allows clinician to a) weigh quantitatively absolute risk reduction intervention b) compare with adverse effects c) do this in a defined population
Level of Evidence in Current Guidelines 80.0% 70.0% 60.0% 50.0% > 90 % of Secondary Prevention Recommendations are Level A or B 40.0% 30.0% 20.0% 10.0% 0.0% 80.0% AF HF PAD STEMI Peri 2nd Pre SA SVA UA A B C 70.0% 60.0% 50.0% 40.0% 30.0% 20.0% 10.0% 0.0% VHD VASCD PCI CABG Pace ExT Echo RnI A B C Scientific Evidence Underlying the ACC/AHA Clinical Practice Guidelines; Tricoci et al.;jama.2009; 301: 831-841.
Patient Groups where RCT Guideline Evidence is Frequently Lacking Women Elderly Racial/Ethnic Groups Multiple Co-Morbidities Procedure Related (Imaging, VHD, CHD)
Patient enrollment in RCTs by different world regions (2011) Among 123196 RCTs registered until 2011, the RCTs in which USA and European countries enrolled patients accounted for 80%, the RCTs that China joined accounted for only 2.3%. www. ClinicalTrials.gov modified by Zhao Dong
7 Enrolling Countries Canada United Kingdom Germany Poland United States France Hungary Czech Republic Romania? New Zealand? Australia 11 Countries, 452 Sites
Relative Risk Reduction in Patients on Active Antihypertensive Treatment vs Placebo or No Treatment 8
Achieved BP and Benefit in Hypertension Trials J Hypertension 2009 25
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) James PA, Oparil S, Carter BL, Cushman WC, Dennison- Himmelfarb C, Handler J, Lackland DT, Lefevre ML, Mackenzie TD, Ogedegbe 13 Pages, O, Smith SC 9 Jr, Recommendations Svetkey LP, Taler SJ, Townsend RR, Wright JT Jr, Narva AS, Ortiz E (only addresses 3 critical questions) JAMA. 2013 Dec 18. doi: 10.1001/jama.2013.284427. [Epub ahead of print]
JNC VII Lifestyle Modifications for BP Control Modification Recommendation Approximate SBP Reduction Range Weight reduction DASH eating plan Maintain normal body weight (BMI=18.5-25) Diet rich in fruits, vegetables, low fat dairy and reduced in fat 5-20 mmhg/10 kg weight lost 8-14 mmhg Restrict sodium intake <2.4 grams of sodium per day 2-8 mmhg Physical activity Regular aerobic exercise for at least 30 minutes most days of the week 4-10 mmhg Moderate alcohol <2 drinks/day for men and <1 drink/day for women 2-4 mmhg BMI=Body mass index, SBP=Systolic blood pressure Chobanian AV et al. JAMA 2003;289:2560-2572 11
Diastolic BP Goal Trials Several trials used DBP goal <90 mm Hg and demonstrated consistent reduction of CVD events, e.g., VA morbidity trial, HDFP, MRC trial,
Major Trials Testing SBP Goals in General Populations SHEP Syst-Eur HYVET JATOS VALISH Age > 60 > 60 > 80 65-85 >70, <85 Number 4,736 4,695 3,845 4,418 3,260 Entry SBP 160-219 160-219 160-199 160 160 Goal SBP <148 <150 <150 <140 <140 Achieved SBP 142 151 144 136 137 Stroke 36% 42% ns ns ns CVD 32% 31% 34% ns ns Mortality ns ns 21% ns ns SBP = systolic blood pressure CVD = cardiovascular disease
Recommendation 1 In the general population 60 years of age, initiate pharmacologic treatment to lower BP at SBP 150 mm Hg or DBP 90 mm Hg and treat to a goal SBP <150 mm Hg and goal DBP <90 mm Hg. Strong Recommendation Grade A Corollary Recommendation: In the general population 60 years of age, if pharmacological treatment for high BP results in lower achieved SBPs (for example, <140 mm Hg) and treatment is not associated with adverse effects on health or quality of life, treatment does not need to be adjusted. Expert Opinion Grade E
2014 Hypertension Guideline Management Algorithm Adult aged 18 years with hypertension Implement lifestyle interventions (continue throughout management). General population (no diabetes or CKD) Set blood pressure goal and initiate blood pressure lowering-medication based on age, diabetes, and chronic kidney disease (CKD). Diabetes or CKD present Age 60 years Age <60 years All ages Diabetes present No CKD All ages CKD present with or without diabetes Blood pressure goal SBP <150 mm Hg DBP <90 mm Hg Blood pressure goal SBP <140 mm Hg DBP <90 mm Hg Blood pressure goal SBP <140 mm Hg DBP <90 mm Hg Blood pressure goal SBP <140 mm Hg DBP <90 mm Hg Nonblack Black All races Initiate thiazide-type diuretic or ACEI or ARB or CCB, alone or in combination. a Initiate thiazide-type diuretic or CCB, alone or in combination. Initiate ACEI or ARB, alone or in combination with other drug class. a Select a drug treatment titration strategy A. Maximize first medication before adding second or B. Add second medication before reaching maximum dose of first medication or C. Start with 2 medication classes separately or as fixed-dose combination.
NICE Guideline - Diagnosis (1) If the clinic blood pressure is 140/90 mmhg or higher, offer ambulatory blood pressure monitoring (ABPM) to confirm the diagnosis of hypertension.
Monitoring drug treatment (1) Use clinic blood pressure measurements to monitor response to treatment. Aim for target blood pressure below: 140/90 mmhg in people aged under 80 150/90 mmhg in people aged 80 and over
Aged under 55 years A Aged over 55 years or black person of African or Caribbean family origin of any age C 2 Step 1 Summary of antihypertensive drug treatment A + C 2 A + C + D Resistant hypertension A + C + D + consider further diuretic 3, 4 or alpha- or beta-blocker 5 Consider seeking expert advice Step 2 Step 3 Step 4 Key A ACE inhibitor or low-cost angiotensin II receptor blocker (ARB) 1 C Calcium-channel blocker (CCB) D Thiazide-like diuretic See slide notes for details of footnotes 1-5
Systolic Blood Pressure Intervention Trial (SPRINT) Multicenter, RCT compares Rx <120 vs. <140 BP Inclusion: 1) age > 50, 2) BP > 130 < 180 and 3) CVD, CKD, 10 y FR>15%, or age > 75 Exclusion: Diabetes or History of Stroke 9361 pts 102 clinics USA, PR; 30%B 36%W 28%>75, 28%CKD, 20%CVD Results: -30% CV Events -25% Mortality -all cause
Major Exclusion Criteria Stroke Diabetes mellitus Polycystic kidney disease Congestive heart failure (symptoms or EF < 35%) Proteinuria >1g/d CKD with egfr < 20 ml/min/1.73m 2 (MDRD) Adherence concerns
Pre-specified Subgroups of Special Interest Age (<75 vs. 75 years) Gender (Men vs. Women) Race/ethnicity (African-American vs. Non African-American) CKD (egfr <60 vs. 60 ml/min/1.73m 2 ) CVD (CVD vs. no prior CVD) Level of BP (Baseline SBP tertiles: 132, 133 to 144, 145 mm Hg)-