To explore the association between use of renin-angiotensin-system inhibitors (RASi) and beta-blockers, with mortality/morbidity in 5 previously identified clusters of patients with heart failure and preserved ejection fraction (HFpEF).
We analysed 20,980 HFpEF patients from the Swedish HF registry, phenotyped into young-low comorbidity burden (12%), atrial fibrillation (AF)-hypertensive (32%), older-AF (24%), obese-diabetic (15%) and a cardio-renal cluster (17%). In Cox proportional hazard models with inverse probability weighting, there was no heterogeneity in the association between RASi use and cluster membership for any of the outcomes: cardiovascular (CV) mortality, all-cause mortality, HF hospitalisation, CV hospitalisation or non-CV hospitalisation. In contrast, we found a statistical interaction between beta-blocker use and cluster membership for all-cause mortality (p-value 0.03) and non-CV hospitalisation (p-value 0.001). In the young-low comorbidity burden and AF-hypertensive cluster, beta-blocker use was associated with statistically significant lower all-cause mortality and non-CV hospitalisation and in the obese-diabetic cluster beta-blocker use was only associated with a statistically significant lower non-CV hospitalisation. The interaction between beta-blocker use and cluster membership for all-cause mortality could potentially be driven by patients improved ejection fraction. However, patient numbers were diminished when excluding those with improved ejection fraction and the direction of the associations remained similar.
In patients with HFpEF, the association with all-cause mortality and non-CV hospitalisation was heterogeneous across clusters for beta-blockers. It remains to be elucidated how heterogeneity in HFpEF could influence personalized medicine and future clinical trial design.

Copyright © 2023. Published by Elsevier Inc.