To the Editor: In a propensity-matched cohort of patients with heart failure with preserved ejection fraction (HFPEF), Dr Lund and colleagues reported that the use of renin-angiotensin system (RAS) antagonists (angiotensin-converting enzyme [ACE] inhibitors or angiotensin II receptor blockers) was associated with lower all-cause mortality.1 Yet multiple prospective randomized placebo-controlled trials have demonstrated no efficacy for mortality with these medications in patients with HFPEF, and a meta-analysis including all randomized controlled trials published to date also found no mortality benefit (hazard ratio, 1.02; 95% CI, 0.94-1.12; P = .60).2 Can there be effectiveness of drugs in clinical practice in the absence of demonstrated efficacy for the same disease state in randomized controlled trials?
Fonarow GC, Ahmed A. Renin-Angiotensin System Antagonists and Mortality in Patients With Heart Failure. JAMA. 2013;309(11):1107–1108. doi:10.1001/jama.2013.1969
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