Effectiveness of angiotensin-neprilysin inhibitor treatment versus renin-angiotensin system blockade in older adults with heart failure in clinical care
Rishi Desai, Elisabetta Patorno, Muthiah Vaduganathan, Mufaddal Mahesri, Kristyn Chin, Raisa Levin, Scott D. Solomon, Sebastian Schneeweiß
Abstract
OBJECTIVE: To evaluate the effectiveness of angiotensin receptor-neprilysin inhibitor (ARNI) versus renin-angiotensin system (RAS) blockade alone in older adults with heart failure with reduced ejection fraction (HFrEF). METHODS: We conducted a cohort study using US Medicare fee-for-service claims data (2014-2017). Patients with HFrEF ≥65 years were identified in two cohorts: (1) initiators of ARNI or RAS blockade alone (ACE inhibitor, ACEI; or angiotensin receptor blocker, ARB) and (2) switchers from an ACEI to either ARNI or ARB. HR with 95% CI from Cox proportional hazard regression and 1-year restricted mean survival time (RMST) difference with 95% CI were calculated for a composite outcome of time to first worsening heart failure event or all-cause mortality after adjustment for 71 pre-exposure characteristics through propensity score fine-stratification weighting. All analyses of initiator and switcher cohorts were conducted separately and then combined using fixed effects. RESULTS: 51 208 patients with a mean age of 76 years were included, with 16 193 in the ARNI group. Adjusted HRs comparing ARNI with RAS blockade alone were 0.92 (95% CI 0.84 to 1.00) among initiators and 0.79 (95% CI 0.74 to 0.85) among switchers, with a combined estimate of 0.84 (95% CI 0.80 to 0.89). Adjusted 1-year RMST difference (95% CI) was 4 days in the initiator cohort (-1 to 9) and 12 days (8 to 17) in the switcher cohort, resulting in a pooled estimate of 9 days (6 to 12) favouring ARNI. CONCLUSION: ARNI treatment was associated with lower risk of a composite effectiveness endpoint compared with RAS blockade alone in older adults with HFrEF.