Association between renin–angiotensin system inhibitor use and mortality/morbidity in elderly patients with heart failure with reduced ejection fraction: a prospective propensity score-matched cohort study

Aims: In heart failure with reduced ejection fraction (HFrEF), renin-angiotensin system inhibitors (RASi) improve morbidity and mortality. However, patients aged >80 years constituted a small minority in trials. We assessed the association between RASi use and mortality/morbidity in HFrEF patients aged >80 years. Methods and results: We included patients with ejection fraction <40% and age >80 years from the Swedish Heart Failure Registry. Propensity scores for RASi use were calculated from 37 variables. Cox regression models for RASi vs. non-RASi with all-cause mortality and all-cause mortality/heart failure (HF) hospitalization as outcomes were fitted in a 1:1 propensity-score-matched cohort. To assess consistency, the same analyses were performed in a 'positive control' cohort aged ≤80 years. Of 6710 patients [median age (interquartile range) 85 (82-87) years; 38% women], 5384 (80%) received RASi. Propensity-score matching yielded 2416 patients, [age 86 (83-91) years]. RASi use was associated with hazard ratio (HR) (95% confidence interval) 0.78 (0.72-0.86) for all-cause mortality and 0.86 (0.79-0.94) for all-cause mortality/HF hospitalization. In positive control patients aged ≤80 years (17 842 patients in the overall cohort, 2126 after matching), HR for all-cause mortality was 0.81 (0.71-0.91), whereas it was 0.85 (0.76-0.94) for all-cause mortality/HF hospitalization. Conclusion: In HFrEF patients with age >80 years, RASi were relatively underused compared with in younger patients, despite similar association with reduced morbidity and mortality and no apparent association with risk of syncope-related hospitalization. These results may be interpreted as hypothesis generating for randomized clinical trials on RASi in this elderly HFrEF subpopulation.