Evidence ProfileARBs + ACEI vs. ACEI + placebo in heart failure with left ventricular systolic dysfunction (LVSD)

Question: Should ARB + ACEI (no BB) vs Placebo + ACEI (no BB) be used for CHF?

Bibliography: H. Krum, P. Carson, C. Farsang, A. P. Maggioni, R. D. Glazer, N. Aknay, Y. T. Chiang, and J. N. Cohn. Effect of valsartan added to background ACE inhibitor therapy in patients with heart failure: results from Val-HeFT. European Journal of Heart Failure 6 (7):937–945, 2004. A. R. Houghton, M. Harrison, A. J. Cowley, and J. R. Hampton. Combined treatment with losartan and an ACE inhibitor in mild to moderate heart failure: results of a double-blind, randomized, placebo-controlled trial. American Heart Journal 140 (5):e25–e31, 2000. McMurray JJ, Ostergren J, Swedberg K, Granger CB, Held P, Michelson EL, Olofsson B, Yusuf S, Pfeffer MA, CHARM Investigators and Committees. Effects of Candesartan in Patients With Chronic Heart Failure and Reduced Left-Ventricular Systolic Function Taking Angiotensin-Converting-Enzyme Inhibitors: the CHARM-Added Trial. Lancet. 2003; 362(9386):767–771.Ref ID 1

Quality assessmentSummary of findingsHazard ratio
No. of patientsEffectQuality
No. of studiesDesignLimitationsInconsistencyIndirectnessImprecisionOther considerationsARB + ACE (no BB)Placebo + ACE (no BB)Relative (95% CI)Absolute
Mortality (follow -up mean 23 months)
2
Val-Heft (subgroup Krum et al)
CHARM-added McMurray
randomised trial1serious1no serious inconsistencyno serious indirectnessno serious imprecisionnone536/2106 (25.5%)555/2063 (26.9%)RR 0.95 (0.85 to 1.05)13 fewer per 1000 (from 40 fewer to 13 more)⊕⊕⊕○
MODERATE
0.93 (0.83 to 1.05)
25.4%12 fewer per 1,000
38.7%19 fewer per 1,000
First hospitalisation (follow-up mean 23 months)
1
Val-Heft
randomised trial1serious1no serious inconsistencyno serious indirectnessserious2none224/1532 (14.6%)315/1502 (21%)RR 0.70 (0.6 to 0.81)63 fewer per 1000 (from 40 fewer to 84 fewer)⊕⊕○○
LOW
Hyperkalaemia (follow-up 41 months)
1
Houghton et al
randomised trialno serious limitationsno serious inconsistencyno serious indirectnessno serious imprecisionnone44/1276 (3.4%)9/1272 (0.7%)RR 4.87 (2.39 to 9.94)27 more per 1000 (from 10 more to 63 more)⊕⊕⊕⊕
HIGH
Increased serum creatinine (umol/L) (follow-up 12 weeks; range of scores: -; Better indicated by less)
1
Houghton et al
randomised trialno serious limitationsno serious inconsistencyno serious indirectnessvery serious3none1010-MD −2.0 (0 to 0)⊕⊕○○
LOW
Quality of Life (MLHQ) (follow-up mean 23 months; measured with: umol/L; range of scores: -; Better indicated by less)
1
Val-Heft
randomised trial1serious1no serious inconsistencyno serious indirectnessno serious imprecisionnone25112499-MD 2.78 (0 to 0)⊕⊕⊕○
MODERATE
1

Subgroup analysis of the Val-HeFT RCT and prespecified subgroup analysis of CHARM-added

2

No explanation was provided

3

No details of SD, SE or effect size CIs given

From: 5, Treating heart failure

Cover of Chronic Heart Failure
Chronic Heart Failure: National Clinical Guideline for Diagnosis and Management in Primary and Secondary Care: Partial Update [Internet].
NICE Clinical Guidelines, No. 108.
National Clinical Guideline Centre (UK).
Copyright © 2010, National Clinical Guideline Centre.

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