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

Michael A. Fuery, Fouad Chouairi, James L. Januzzi, Gordon W. Moe, Cesar Caraballo, Megan McCullough, P. Elliott Miller, Samuel W. Reinhardt, Katherine Clark, Andrew Oseran, Aidan Milner, Justin Pacor, Peter A. Kahn, Avinainder Singh, Neal Ravindra, Avirup Guha, Lina Vadlamani, Neeti S. Kulkarni, Mona Fiuzat, G. Michael FelkerChristopher M. O'Connor, Tariq Ahmad, Justin Ezekowitz, Nihar R. Desai

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


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)
Original languageEnglish (US)
Pages (from-to)497-505
Number of pages9
JournalJACC: Heart Failure
Issue number7
StatePublished - Jul 1 2021


  • Canada
  • United States
  • guideline-directed medical therapy
  • heart failure and reduced ejection fraction


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