Geographic variations in the PARADIGM-HF heart failure trial

Area of Science:

• Cardiology
• Clinical Trials
• Global Health

Background:

• Globalization of clinical trials reveals geographic variations in patient characteristics, event rates, and treatment effects.
• The PARADIGM-HF trial is the largest and most globally representative study conducted in heart failure (HF) to date.

Purpose of the Study:

• To investigate geographic variations in patient characteristics, event rates, and treatment effects within the PARADIGM-HF trial.
• To assess the consistency of sacubitril/valsartan treatment benefit across different global regions.

Main Methods:

• Analysis of patient data from five distinct global regions: North America (NA), Western Europe (WE), Central/Eastern Europe/Russia (CEER), Latin America (LA), and Asia-Pacific (AP).
• Comparison of demographic data, comorbidity profiles, symptom severity, functional status, and use of background therapies across regions.
• Evaluation of primary composite outcome rates (CV death or HF hospitalization) and treatment effects of sacubitril/valsartan, adjusted for prognostic variables.

Main Results:

• Significant regional differences observed in patient age, prevalence of coronary disease, symptom severity, functional status, and use of devices (e.g., defibrillators) and medications (e.g., mineralocorticoid receptor antagonists).
• Event rates for cardiovascular death or heart failure hospitalization varied across regions, with higher risks in LA and AP relative to NA after adjustment.
• The risk of heart failure hospitalization was lower in WE compared to NA.
• The clinical benefit of sacubitril/valsartan was found to be consistent across all investigated geographic regions.

Conclusions:

• PARADIGM-HF demonstrated substantial regional heterogeneity in heart failure patient populations and outcomes.
• Despite observed differences, the efficacy of sacubitril/valsartan in reducing cardiovascular death or heart failure hospitalization was consistent globally.
• These findings underscore the importance of considering regional factors in clinical trial design and interpretation while confirming the universal benefit of sacubitril/valsartan in heart failure management.