Comparative analysis of randomized versus real-world populations in heart failure: DIAMOND trial vs CARE-HK registry.

INTRODUCTION

The DIAMOND randomized controlled trial (RCT) found patiromer to effectively reduce the risk of hyperkalaemic events among patients with heart failure (HF). However, the extent to which the RCT population reflects routine clinical practice remains unclear. We aimed to compare eligibility, clinical profile, and treatment patterns between patients enrolled in the CARE-HK registry and the DIAMOND trial.

METHODS

DIAMOND (NCT03888066), a Phase 3b RCT completed in 2021, and CARE-HK (NCT04864795), a non-interventional registry completed in 2024, both enrolled patients with chronic HF and either active hyperkalaemia or high risk for hyperkalaemia.

RESULTS

Only 17.2% of CARE-HK participants met DIAMOND's eligibility criteria, dropping to 3.4% when excluding patients with missing data. Compared with DIAMOND, CARE-HK enrolled an older (71.8 vs 67.2 years), more diverse population with more women (31.5% vs 27.6%) and greater burden of comorbidities. Patients exhibited more advanced renal dysfunction, especially in the HF with reduced ejection fraction (HFrEF) population. Within CARE-HK, the use of angiotensin receptor-neprilysin inhibitors (72.1% vs 17.0%), sodium-glucose transport protein 2 inhibitors (69.0% vs 6.6%), and quadruple therapy (47.4% vs 3.9%) was higher in the HFrEF subgroup than in DIAMOND. Despite some progress in prescribing practices, uptake in guideline-directed medical therapy remained incomplete, especially within HFrEF, and renin-angiotensin-aldosterone system inhibitor dosing was often suboptimal.

CONCLUSION

This study underscores the value of real-world evidence in complementing RCTs by offering insights into population diversity, comorbidity burden, and prescription behaviours, and highlights the need for more pragmatic and inclusive trials in HF.