TY - JOUR
T1 - 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?
AU - UIJL, A. LI. CI. A.
AU - KOUDSTAAL, S. TE. FA. N.
AU - STOLFO, D. AV. ID. E.
AU - DAHLSTRÖM, U. L. F.
AU - VAARTJES, I. LO. NC. A.
AU - GROBBEE, R. IC. K. E.
AU - ASSELBERGS, F. OL. KE. RT W.
AU - LUND, L. AR. S. H.
AU - SAVARESE, G. IA. NL. UI. GI
N1 - Funding Information: This work was supported by the EU/EFPIA Innovative Medicines Initiative 2 Joint Undertaking BigData@Heart grant n° 116074 . F. W. Asselbergs is supported by UCL Hospitals NIHR Biomedical Research Centre . I. Vaartjes is supported by the Dutch Heart Foundation , as part of “Facts and Figures.” Publisher Copyright: © 2023 The Author(s)
PY - 2023/8/25
Y1 - 2023/8/25
N2 - 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.
AB - 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.
KW - HFpEF
KW - Phenotype clusters
KW - beta-blockers
KW - personalized medicine
KW - renin–angiotensin system inhibitors
UR - http://www.scopus.com/inward/record.url?scp=85171560029&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.cardfail.2023.08.008
DO - https://doi.org/10.1016/j.cardfail.2023.08.008
M3 - Article
C2 - 37634573
SN - 1071-9164
JO - Journal of Cardiac Failure
JF - Journal of Cardiac Failure
ER -