Elsevier

JACC: Heart Failure

Volume 9, Issue 7, July 2021, Pages 497-505
JACC: Heart Failure

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

https://doi.org/10.1016/j.jchf.2021.02.011Get rights and content
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Abstract

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)

Key Words

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

Abbreviations and Acronyms

ACE
angiotensin-converting enzyme
ARB
angiotensin II receptor blocker
CI
confidence interval
GDMT
guideline-directed medical therapy
HF
heart failure
HFrEF
heart failure with reduced ejection fraction
HR
hazard ratio
IQR
interquartile range
MRA
mineralocorticoid receptor antagonist
NT-proBNP
N-terminal pro–B-type natriuretic peptide

Cited by (0)

John Teerlink, MD, served as the Guest Editor for this paper.

The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.

Drs. Ezekowitz and Desai are joint senior authors.