In Reply: The efficacy of RAS antagonists in HFPEF remains controversial. Our study should be interpreted in light of other evidence and within the methodological constraints of nonrandomized studies. In the article, we discussed at length the randomized controlled trials and meta-analyses that have been published on the topic, which both support and contrast with our findings, and limitations of our study.
Drs Fonarow and Ahmed call particular attention to 2 negative studies. The study by Patel et al1 assessed angiotensin II receptor blockers and not ACE inhibitors. It had only 296 patient pairs (compared with 3329 in our study) and the point estimate for the hazard ratio for all-cause mortality (0.93) was similar to ours (0.91), but their low power yielded a nonsignificant 95% CI (0.76-1.14) compared with ours (0.85-0.98). Furthermore, that study did not adjust for fundamental clinical and socioeconomic confounders such as treatment dose, New York Heart Association class, marital and living arrangements, and follow-up care. In addition, in our study, 75% of RAS antagonist treatment was ACE inhibitors, which may be more effective than angiotensin II receptor blockers.