Association between use of renin-angiotensin system inhibitors/angiotensin receptor neprilysin inhibitors and beta-blockers and outcome in real-world heart failure and mildly reduced ejection fraction

Abstract Background In heart failure with mildly reduced ejection fraction (HFmrEF) European guidelines recommend the use of antineurohormonal therapies a low level evidence (IIb C) based on data from subgroup and post-hoc analyses randomized clinical trials (RCTs). Data large unselected real-world HFmrEF populations are lacking. Purpose To assess association between renin-angiotensin system inhibitors/angiotensin receptor neprilysin inhibitors (RASI/ARNI) beta-blockers outcomes in HFmrEF. Methods patients (EF: 40–49%) Swedish HF Registry during 2000–2018 were considered. The each RASI/ARNI treatment cardiovascular (CV)mortality/heart hospitalization (HFH) all-cause mortality was assessed by Cox proportional hazard models 1:1 propensity score-matched cohort. Since score (PS) matching might lead to selection study population reduction sample size, as consistency analysis also fitted overall cohort adjusting rather than for PS. Results Of 12421 (mean age 74±12 years, 64% males), 10419 (84%) received RASI/ARNI, 10941 (88%) beta-blockers. Patients treated both 9332 (75%), 2696 (22%) one drug (9% 13% beta-blockers) 393 (3%) none. Main predictors treatments younger age, female sex (only beta-blockers), outpatient setting, referral specialty care nurse-led clinic. Lower NT-proBNP levels associated more but less Better renal function predictive use. Comorbidities treatments, particular atrial fibrillation COPD matched cohorts including 3854 2940 beta-blockers, (HR=0.90, 95% CI: 0.83–0.97) beta-blocker (HR=0.82, 0.75–0.91) statistically significant lower risk CV mortality/HF (Figure 1) (HR=0.72, 0.67–0.78 HR=0.77, 0.70–0.85, respectively). Consistency confirmed results. Conclusions largely used this treat comorbidities. Their mortality/morbidity magnitude associations somehow similar what observed subgroup/post-hoc RCTs. Our findings call fast implementation recommendations treatment. Funding Acknowledgement Type funding sources: None.