Heart failure drugs work differently depending on patient type, study finds
A Swedish study of nearly 21,000 heart failure patients reveals that beta-blockers—a cornerstone treatment—show dramatically different effectiveness across patient subgroups, while a competing drug class works uniformly. The finding could reshape how doctors prescribe these medications and signals opportunities for personalized treatment strategies in a major disease affecting millions.
Originaltitel: 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?
<p><strong>Background</strong></p><p>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).</p><p><strong>Methods and Results</strong></p><p>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.</p><p><strong>Conclusions</strong></p><p>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.</p><p></p><p><strong>Graphical abstract</strong></p><p>AF = atrial fibrillation; CI = % confidence interval; CV = cardiovascular; DM = diabetes; HF = heart failure; HFpEF = Heart failure with preserved ejection fraction; HR = hazard ratio; HT = hypertension; RAS = renin–angiotensin system.</p><p><strong></strong></p><p><img src="https://ars.els-cdn.com/content/image/1-s2.0-S1071916423003044-ga1.jpg" /></p>