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Intercountry Differences in Guideline-Directed Medical Therapy and Outcomes Among Patients With Heart Failure
Michael A Fuery1, Fouad Chouairi2, James L Januzzi3
1Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
Insights
Patients with heart failure with reduced ejection fraction (HFrEF) in Canada had fewer hospitalizations than those in the U.S. Differences in care and patient demographics influenced these heart failure outcomes.
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.
Objectives:
The aim of this study was to examine patterns of care and clinical outcomes among patients with heart failure with reduced ejection fraction (HFrEF) in the United States and Canada.
Background:
In the GUIDE-IT (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment) trial, the use of N-terminal pro-B-type natriuretic peptide-guided titration of guideline-directed medical therapy (GDMT) was compared with usual care alone for patients with HFrEF in the United States and Canada. It remains unknown whether the country of enrollment had an impact on outcomes or GDMT use.
Methods:
A total of 894 patients at 45 sites across the United States and Canada with HFrEF (ejection fraction ≤40%) were enrolled in the trial. Kaplan-Meier survival estimates stratified by country of enrollment were developed for the trial outcomes, and log-rank testing was compared between the groups. GDMT use and titration were also compared.
Results:
U.S. patients were more likely to be younger, to be Black, to have higher body mass index, and to have histories of defibrillator placement or sleep apnea. Use of β-blockers was significantly higher in Canada at baseline (99.3% vs. 94.0%; p = 0.01) and 6 months (99.0% vs. 94.1%; p = 0.04), and use of mineralocorticoid receptor antagonists was higher in Canada at 6 months (68.3% vs. 55.1%; p = 0.01). Canadian patients were less likely to experience the primary study endpoint (hazard ratio [HR]: 0.65; 95% confidence interval [CI]: 0.45 to 0.93; p = 0.01) due to decreased rates of HF hospitalization (HR: 0.57; 95% CI: 0.38 to 0.86; p = 0.003). The differences in outcomes were driven by increased heart failure hospitalization among U.S. Black patients.
Conclusions:
In GUIDE-IT, patients with HFrEF in Canada were significantly less likely to be hospitalized for heart failure. Differences in GDMT use, along with differences in sociodemographics and care delivery structures, may contribute to these differences, highlighting the importance of increasing diversity in clinical trials. (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment [GUIDE-IT]; NCT01685840).
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