Intercountry Differences in Guideline-Directed Medical Therapy and Outcomes Among Patients With Heart Failure

Area of Science:

• Cardiology
• Clinical Trials
• Health Services Research

Background:

• The GUIDE-IT trial compared N-terminal pro-B-type natriuretic peptide-guided therapy to usual care for heart failure with reduced ejection fraction (HFrEF).
• Impact of country of enrollment (United States vs. Canada) on outcomes and guideline-directed medical therapy (GDMT) use in HFrEF was previously unknown.

Purpose of the Study:

• To examine differences in patterns of care and clinical outcomes for HFrEF patients between the United States and Canada within the GUIDE-IT trial.
• To investigate if country of enrollment influenced GDMT use and patient outcomes in HFrEF.

Main Methods:

• Analysis of 894 HFrEF patients enrolled across 45 sites in the United States and Canada.
• Comparison of Kaplan-Meier survival estimates and log-rank testing stratified by country.
• Assessment of guideline-directed medical therapy (GDMT) use and titration between U.S. and Canadian cohorts.

Main Results:

• U.S. patients had distinct sociodemographic profiles, including younger age, higher prevalence of Black race, and higher BMI.
• Canadian patients showed higher use of beta-blockers and mineralocorticoid receptor antagonists.
• Canadian patients experienced significantly lower rates of the primary endpoint, primarily driven by reduced heart failure hospitalizations, particularly among U.S. Black patients.

Conclusions:

• Patients with HFrEF in Canada had significantly lower heart failure hospitalization rates compared to those in the U.S.
• Disparities in GDMT use, sociodemographics, and healthcare delivery may explain outcome differences.
• The findings underscore the need for greater diversity in clinical trials to ensure generalizability of results.