Comparative Analysis of Randomized versus Real World Populations in Heart Failure: DIAMOND Trial versus CARE-HK Registry

Abstract Aims The DIAMOND randomized controlled trial (RCT) found patiromer to effectively reduce risk of hyperkalemia among patients with heart failure (HF) at high-risk for hyperkalemic events. 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 and results 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 hyperkalemia or high risk for hyperkalemia. Only 17.2% of CARE-HK participants met DIAMOND’s eligibility criteria, dropping to 3.4% when excluding patients with missing data. Compared to 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 inhibitors dosing was often suboptimal. Conclusions 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.