Association Between Use of Renin-Angiotensin System Antagonists and Mortality in Patients With Heart Failure and Preserved Ejection Fraction

Study Questions:

Do renin-angiotensin (RAS-I) antagonists impact mortality in patients with heart failure and preserved ejection fraction (HFPEF)?


This was a prospective analysis of the Swedish Heart Failure Registry. There were 16,216 patients with HFPEF (left ventricular ejection fraction ≥40%), of whom 12,543 were treated with a RAS-I (angiotensin-converting enzyme inhibitor [ACE] or angiotensin-receptor blocker [ARB]) and 3,673 were not. Age and propensity score matching were undertaken (1:1), and the impact of RAS-I on mortality was analyzed.


Of the 12,543 patients on RAS-I therapy, 73% were treated with an ACE inhibitor and 25% an ARB. One-year survival in the unmatched HFPEF cohort was 86% (95% confidence interval [CI], 68-71%) in RAS-I treated patients and 69% in nontreated patients (adjusted hazard ratio [HR], 0.90; 95% CI, 0.85-0.96 with RAS-I therapy). In the propensity-matched cohort, 1-year survivals were 77% and 72%, respectively (HR, 0.91; 95% CI, 0.85-0.98 with RAS-I therapy). In patients receiving <50% target RAS-I dose, the impact on mortality was less (HR, 0.94; 95% CI, 0.87-1.02 compared with no therapy) than those who received higher dosing (HR, 0.85; 95% CI, 0.78-0.83 compared with no therapy).


The authors concluded that patients with HFPEF treated with RAS-I had lower mortality.


HFPEF is a prevalent disease with considerable morbidity and mortality. Unfortunately, no pharmacologic interventions have been identified that significantly improve HFPEF outcomes. In this large prospective cohort study, treatment of patients with HFPEF appeared to offer a 10% decrease in mortality at 1 year. A very clear difference in outcomes was apparent for RAS-I use in the unmatched cohort (HR, 0.48 for mortality with therapy) versus that of those analyzed with propensity matching (HR, 0.91 for mortality with therapy). Thus, there are likely several factors that weigh into the decision to prescribe or not prescribe a RAS-I in HFPEF. In this analysis, patients prescribed RAS-I were younger, and had better renal function, higher blood pressures, and better New York Heart Association class—overall they were less ill. The next step is to use this information to design a study looking at RAS-I use in a targeted HFPEF population based on the information gleaned in the current study.

Clinical Topics: Dyslipidemia, Heart Failure and Cardiomyopathies, Prevention, Lipid Metabolism, Novel Agents, Statins, Acute Heart Failure, Hypertension

Keywords: Renin, Renin-Angiotensin System, Blood Pressure, New York, Receptors, G-Protein-Coupled, Triazines, Heart Diseases, Proto-Oncogene Proteins, Heart Failure, Follicle Stimulating Hormone, Hypertension, Luteinizing Hormone, Sulfonamides

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