Efficacy of renin–angiotensin system inhibitors for patients with heart failure with preserved ejection fraction and mild to moderate chronic kidney disease

Background Renin-angiotensin system (RAS) inhibitors are first-line treatments for chronic kidney disease, but it is not known if these agents can improve outcome in patients with heart failure with preserved ejection fraction (HFpEF) and chronic kidney disease. Design This was a post-hoc analysis of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial. Methods The primary outcome was a composite endpoint of all-cause death, non-fatal myocardial infarction, non-fatal stroke or hospitalization for heart failure. We analyzed hazard ratios in patients taking RAS inhibitors compared with those not taking RAS inhibitors using Cox proportional hazard models. Results A total of 1465 HFpEF patients with mild to moderate chronic kidney disease was included. The mean follow-up period was 2.8 years; 502 patients experienced at least one confirmed primary outcome event. The primary outcome event rates in patients not taking and taking RAS inhibitors were 175.4 and 112.8 per 1000 person-years, respectively. The risks of primary outcome events and all-cause death were significantly lower in patients taking RAS inhibitors than in those not taking RAS inhibitors (adjusted hazard ratio (95% confidence interval) for primary outcome events: 0.75 (0.60-0.95), p = 0.01; adjusted hazard ratio for all-cause death: 0.69 (0.52-0.93), p = 0.01). Among propensity score-matched patients, these risks were also significantly lower in those taking RAS inhibitors than in those not taking RAS inhibitors (hazard ratio: 0.67 (0.50-0.90), p = 0.008; hazard ratio: 0.60 (0.41-0.88), p = 0.01). Conclusion Use of RAS inhibitors was associated with reduced risks of adverse cardiovascular outcomes in HFpEF patients with mild to moderate chronic kidney disease.