1. Does Heterogeneity Exist in Treatment Associations With Renin-Angiotensin-System Inhibitors or Beta-blockers According to Phenotype Clusters in Heart Failure with Preserved Ejection Fraction?
- Author
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Uijl A, Koudstaal S, Stolfo D, Dahlström U, Vaartjes I, Grobbee RE, Asselbergs FW, Lund LH, and Savarese G
- Subjects
- Humans, Renin therapeutic use, Stroke Volume, Adrenergic beta-Antagonists therapeutic use, Obesity drug therapy, Angiotensins therapeutic use, Heart Failure drug therapy, Heart Failure epidemiology, Atrial Fibrillation drug therapy, Atrial Fibrillation epidemiology, Diabetes Mellitus drug therapy
- Abstract
Background: We explored the association between use of renin-angiotensin system inhibitors and beta-blockers, with mortality/morbidity in 5 previously identified clusters of patients with heart failure with preserved ejection fraction (HFpEF)., Methods and Results: We analyzed 20,980 patients with HFpEF from the Swedish HF registry, phenotyped into young-low comorbidity burden (12%), atrial fibrillation-hypertensive (32%), older-atrial fibrillation (24%), obese-diabetic (15%), and a cardiorenal cluster (17%). In Cox proportional hazard models with inverse probability weighting, there was no heterogeneity in the association between renin-angiotensin system inhibitor 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 = .03) and non-CV hospitalisation (P = .001). In the young-low comorbidity burden and atrial fibrillation-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 with improved EF. However, patient numbers were diminished when excluding those with improved EF and the direction of the associations remained similar., Conclusions: 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., Competing Interests: Declaration of Competing Interest AU, SK, IV, DG, and FA have nothing to disclose. DS reports personal fees from Novartis, Acceleron, and Merck, none related to the present work. UD reports grants from AstraZeneca, Boehringer Ingelheim, Pfizer, Vifor, Boston Scientific, and Roche Diagnostics and personal fees from Novartis, AstraZeneca, and Amgen, outside the submitted work. LHL reports personal fees from Merck, grants and personal fees from Boehringer Ingelheim, personal fees from Sanofi, grants and personal fees from Vifor-Fresenius, personal fees from AstraZeneca, grants and personal fees from Relypsa, personal fees from Bayer, grants from Boston Scientific, grants and personal fees from Novartis, personal fees from Pharmacosmos, personal fees from Abbott, grants and personal fees from Mundipharma, and personal fees from Medscape, outside the submitted work. GS reports grants and personal fees from Vifor, grants and nonfinancial support from Boehringer Ingelheim, personal fees from Societa´ Prodotti Antibiotici, grants and personal fees from AstraZeneca, personal fees from Roche, personal fees from Servier, grants from Novartis, grants from Boston Scientific, personal fees from GENESIS, personal fees from Cytokinetics, personal fees from Medtronic, grants from Boston Scientific, grants from PHARMACOSMOS, grants from Merck, and grants from Bayer, outside the submitted work., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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