Heart failure with reduced ejection fraction (HFrEF) is a major global health challenge associated with substantial rates of morbidity and mortality worldwide. Multinational clinical trials of this condition face a significant hurdle: patient demographics, access to high-quality care, and baseline health all vary drastically by region. This regional heterogeneity can skew survival rates and potentially alter the efficacy of new drug therapies, making the traditional use of geographic regions for analysis an inadequate tool.
To address this critical issue, a recent secondary analysis of the VICTORIA trial investigated how patient profiles, standard of care, and the treatment effect of the drug vericiguat versus placebo may vary across geographic regions. Researchers analyzed data from 5,050 participants across 42 countries, classifying them into five prespecified geographic regions. The core aim was to determine if these regional and developmental differences could explain observed variations in the drug’s efficacy on clinical outcomes, specifically heart failure hospitalization and cardiovascular death. As an alternative to region, a country’s human development index (HDI) (i.e., a composite measure of life expectancy, education, and standard of living) was examined for its relationship with treatment efficacy.
While the analysis confirmed significant variations in patient characteristics and existing care standards across the five geographic regions, the overall efficacy of vericiguat remained broadly consistent across these groupings. However, further examination of the country-level HDI revealed a significant finding: the drug’s benefit against heart failure hospitalization and the combined primary endpoint decreased with rising HDI, whereas the positive effect on cardiovascular death remained unchanged. These findings suggest that systemic, contextual measures like HDI offer vital insights for planning future trials and ensuring high-quality evidence translates into optimal and equitable clinical practice worldwide.
This research was led by Cindy Westerhout, PhD, and co-authored by fellow CVC members Wendimagegn Alemayehu, PhD, Justin Ezekowitz, MBBCh, MSc, and Paul Armstrong, MD, together with Alain Cohen-Solal, MD, PhD (Université Paris Cité), Carolyn Lam, MBBS, PhD (National Heart Centre Singapore), Stefano Corda, MD, PhD (Bayer AG), Ciaran McMullan, MD (Merck & Co., Inc.), and Christopher O’Connor, MD (Inova Schar Heart and Vascular Institute).
