Country Income Level, Protocol Completion, and Trial Endpoints Among Patients With Acute Heart Failure: Insights From the ASCEND-HF Trial

Introduction: Globalization of clinical trials fosters inclusion of patients from higher and lower income countries. The influence of enrolling country income level on heart failure (HF) trial performance is unclear.Methods: Associations between country income level, patient characteristics, protocol non-completion, and endpoints were assessed among 7,064 pts from 29 countries in the ASCEND-HF trial. Country income data and classifications (in gross national income per capita in current US dollars) from the year 2007 (i.e., the year trial enrollment began) were abstracted from the World Bank. Patients were grouped by enrolling country income level (i.e., high [>$11,455], upper-middle [$3,706-$11,455], and lower-middle [$936-$3,705]).Results: Overall, there were 3996 (57%), 1518 (21%), and 1550 (22%) patients from high, upper-middle, and lower-middle income countries, respectively. There were no patients from low income countries. Patients from lower-middle income countries tended to be younger with lower baseline blood pressure, worse NYHA functional class, and fewer comorbidities. Every $10,000 increase in country income was associated with an increase in protocol non-completion (OR 1.19, 95% CI 1.00-1.41). After adjustment for race, geographic region, and clinical characteristics, increasing country income level was associated with increased 30-day death or rehospitalization, but not 180-day mortality (Table). The association between higher country income and the 30-day endpoint was similar across geographic regions, except Latin America where an inverse association was seen (OR 0.14, 95% CI 0.03-0.78) (p for interaction=0.03).Conclusions: In this acute HF trial, patients from higher income countries had lower rates of protocol completion and worse 30-day outcomes, independent of race and geographic region. Variation in country income level is a challenge to be considered in global HF trials.Author Disclosures: S.J. Greene: None. A.F. Hernandez: Other Research Support; Significant; Novartis, Portola Pharmaceuticals, Bristol-Myers Squibb, AHA, Aires Pharmaceuticals, Amgen, AstraZeneca, Genentech, GlaxoSmithKline, Merck & Co., NHLBI, PCORI, Sanofi. Consultant/Advisory Board; Modest; Amgen, AstraZeneca, Bayer Corporation, Boehringer Engelheim, Boston Scientific, MyoKardia, Pfizer, Pluristem Therapeutics, Sanofi, Sensible. Consultant/Advisory Board; Significant; Novartis. J. Sun: None. J. Butler: Research Grant; Significant; NIH, European Union. Consultant/Advisory Board; Modest; Amgen, AstraZeneca, Merck, Relypsa, ZS Pharma. Consultant/Advisory Board; Significant; Bayer, Boehringer Inhelheim, Novartis, Janssen. P.W. Armstrong: None. J.A. Ezekowitz: Other Research Support; Modest; Astra Zeneca,Amgen, Abbott, Servier, Johnson & Johnson, Pfizer, BMS. Honoraria; Modest; Astra Zeneca,Amgen, Abbott, Servier, Johnson & Johnson, Pfizer, BMS. Other; Modest; Astra Zeneca,Amgen, Abbott, Servier, Johnson & Johnson, Pfizer, BMS. F. Zannad: Honoraria; Significant; Roche Diagnostic. J.P. Ferreira: None. A. Coles: None. M. Metra: None. A.A. Voors: Research Grant; Significant; Novartis. R.M. Califf: None. C.M. O’Connor: None. R.J. Mentz: Research Grant; Significant; National Institutes of Health (grants U10HL110312 and R01AG045551-01A1), Amgen, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Gilead, Novartis, Otsuka, and ResMed. Honoraria; Modest; HeartWare, Janssen, Luitpold Pharmaceuticals, Novartis, ResMed, and Thoratec/St. Jude.

Duke Scholars

Author Stephen Greene Medicine, Cardiology

Author Adrian Felipe Hernandez Medicine, Cardiology

Author Robert John Mentz Medicine, Cardiology