Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
JACC Heart Fail. 2021 Jul;9(7):497-505. doi: 10.1016/j.jchf.2021.02.011. Epub 2021 May 12.
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.
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.
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.
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.
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).
本研究旨在考察美国和加拿大射血分数降低的心力衰竭（HFrEF）患者的治疗模式和临床结局。
在 GUIDE-IT（使用生物标志物强化治疗指导证据的治疗）试验中，与单独接受常规治疗相比，N 端脑利钠肽前体指导下的指南指导的药物治疗（GDMT）滴定用于美国和加拿大的 HFrEF 患者。尚不清楚入组国家是否对结局或 GDMT 使用有影响。
该试验共纳入美国和加拿大 45 个地点的 894 例 HFrEF（射血分数≤40%）患者。按入组国家分层，绘制试验结局的 Kaplan-Meier 生存估计，并对组间进行对数秩检验。还比较了 GDMT 的使用和滴定。
与美国患者相比，加拿大患者更年轻、更可能为黑人、体重指数更高、有心脏除颤器植入或睡眠呼吸暂停病史。加拿大患者在基线时（99.3%比 94.0%；p=0.01）和 6 个月时（99.0%比 94.1%；p=0.04）β受体阻滞剂的使用率显著更高，6 个月时使用盐皮质激素受体拮抗剂的比例更高（68.3%比 55.1%；p=0.01）。加拿大患者因心力衰竭住院率降低，更不可能出现主要研究终点（风险比 [HR]：0.65；95%置信区间 [CI]：0.45 至 0.93；p=0.01）（HR：0.57；95%CI：0.38 至 0.86；p=0.003）。结局的差异是由于美国黑人患者心力衰竭住院率增加所致。
在 GUIDE-IT 中，加拿大的 HFrEF 患者因心力衰竭住院的可能性显著降低。GDMT 使用的差异，以及社会人口统计学和医疗服务结构的差异，可能导致了这些差异，突出了在临床试验中增加多样性的重要性。（使用生物标志物强化治疗指导证据的治疗[GUIDE-IT]；NCT01685840）。
