U-M Ambulatory Care APPE Journal Club
Systolic Blood Pressure and Cardiovascular Outcomes During Treatment of Hypertension
Richard C. Walls
I) Background
A) Hypertension
1) Blood pressure ≥ 140/90 mmHg1
2) Affects 31% of Americans, risk of developing after age 55: 90%1
3) Increased risk of stroke, MI, angina, heart failure, kidney failure, early CV death seen at
SBP as low as 1152
4) Treatment
(i) Goal BP: JNC7—<140/90; <130/80 w/DM or CKD3
(ii) Limited clinical trial evidence correlating BP reduction with outcomes
(a) ACCORD: <120 vs. <140 HRs—stroke 0.59 p=0.01 CV outcomes—0.88 p=0.2,
any cause mortality—1.07 p=0.55, serious adverse events 3.3% vs. 1.3% p<0.0014
(b) ONTARGET: Patients with baseline SBP ≤ 130 HR for any decrease in SBP:
CV mortality—2.11 p<0.001, MI—0.81 p=0.127, stroke—0.85 p=0.3815
B) ACCOMPLISH Trial6
1) RCT: benazepril & amlodipine vs. benazepril & hydrochlorothiazide
2) High risk patients7
(i) History of ACS, CABG, PCI, stroke, or DM
(ii) Baseline characteristics: BP – 145/80, Age 68, BMI 31
3) BP reduction protocol: Randomized -> Wash out -> benazepril 20 mg + HCTZ 12.5
mg/amlodipine 5 mg -> benazepril 40 mg -> increase HCTZ/amlodipine if necessary to
reach target -> add additional antihypertensive if necessary to reach target
(i) Target BP <140/90, <130/80 encouraged w/DM or CKD
(ii) Medications titrated over 3 months, follow up 3 mo. after, then every 6 mo. until
complete
4) Primary outcome: time to composite of CV death, nonfatal MI/stroke
5) Secondary outcomes: CV death, all-cause mortality, total stroke, total MI, increased SCr
(>50% increase from baseline)
II) Summary of Trial8
A) Objective: Evaluate CV outcomes at various BP levels in high risk patients
B) Methods and statistical analysis
1) Preplanned prospective cohort analysis of RCT data
2) Pooled data from both ACCOMPLISH treatment groups (n=11,506), analyzed SBP in
groups: ≥140 (n=2354), 130-139 (n=3429), 120-129 (n=3593), 110-119 (n=1329),
patients <110 not evaluated (n=237)
3) Event rates compared to adjacent ranges, and all ranges compared to SBP ≥140
4) Intention-to-treat analysis, Cox regression to attain HR w/95% CI
C) Results
1) Lower baseline BP associated with lower achieved BP on treatment
2) Clinical outcomes
(i) 130-139 superior to >140 for primary endpoint [HR 0.62 (0.50-0.77)] as well as CV
death, all-cause mortality, total MI, total stroke, coronary events, and increased SCr
(ii) 120-129 vs. 130-139 increased SCr only significant difference [HR 1.29 (1.12-1.49)]
(iii) 110-119 vs. 120-129 increased all-cause mortality, total MI, clinical coronary events,
increased SCr; non-statistically significant decreased risk of stroke [HR 0.60 (0.351.01)]
D) Authors’ Conclusions
1) Clear benefit to targeting SBP <140
2) Targeting SBP <130 has no clear CV benefits and worsens renal outcomes
3) Reduced rate of stroke at <120 difficult to justify in light of increase coronary events
III) Analysis of Trial
A) Strengths and Limitations of Trial
1) Strengths: Large sample size, meaningful comparator groups, meaningful outcomes,
reasonable methods with convincing data
2) Limitations: Cohort study, applicability to non-high risk patients with HTN limited,
applicability to other high risk populations? (HF?), surrogate marker for renal outcomes,
any impact of specific antihypertensives?, what about <110?
B) Possible conflicts of interest: many authors consultants/employees of pharmaceutical
companies, ACCOMPLISH funded by Novartis
C) My conclusions
1) Difficult to recommend changing practice based on one cohort study
2) Evidence beginning to come out that lower BP is not always better
3) Gives me a reason to question unchecked pushing BP lower and lower and to keep an
eye on developing evidence regarding BP and outcome correlations
References
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Am J Med. 2013:126(6):501-8