REDCUE-IT 美国研究：3146 例美国患者随机分组结果。
REDUCE-IT USA: Results From the 3146 Patients Randomized in the United States.
机构信息
Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, MA (D.L.B.).
Department of Medicine, University of Maryland School of Medicine, Baltimore (M.M.).
出版信息
Circulation. 2020 Feb 4;141(5):367-375. doi: 10.1161/CIRCULATIONAHA.119.044440. Epub 2019 Nov 11.
BACKGROUND
Some trials have found that patients from the United States derive less benefit than patients enrolled outside the United States. This prespecified REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl - Intervention Trial) subgroup analysis was conducted to determine the degree of benefit of icosapent ethyl in the United States.
METHODS
REDUCE-IT randomized 8179 statin-treated patients with qualifying triglycerides ≥135 and <500 mg/dL and low-density lipoprotein cholesterol >40 and ≤100 mg/dL and a history of atherosclerosis or diabetes mellitus to icosapent ethyl 4 g/d or placebo. The primary composite end point was cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or hospitalization for unstable angina. The key secondary composite end point was cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. A hierarchy was prespecified for examination of individual and composite end points.
RESULTS
A total of 3146 US patients (38.5% of the trial) were randomized and followed for a median of 4.9 years; 32.3% were women and 9.7% were Hispanic. The primary composite end point occurred in 24.7% of placebo-treated patients versus 18.2% of icosapent ethyl-treated patients (hazard ratio [HR], 0.69 [95% CI, 0.59-0.80]; =0.000001); the key secondary composite end point occurred in 16.6% versus 12.1% (HR, 0.69 [95% CI, 0.57-0.83]; =0.00008). All prespecified hierarchical end points were meaningfully and significantly reduced, including cardiovascular death (6.7% to 4.7%; HR, 0.66 [95% CI, 0.49-0.90]; =0.007), myocardial infarction (8.8% to 6.7%; HR, 0.72 [95% CI, 0.56-0.93]; =0.01), stroke (4.1% to 2.6%; HR, 0.63 [95% CI, 0.43-0.93]; =0.02), and all-cause mortality (9.8% to 7.2%; HR, 0.70 [95% CI, 0.55-0.90]; =0.004); for all-cause mortality in the US versus non-US patients, =0.02. Safety and tolerability findings were consistent with the full study cohort.
CONCLUSIONS
Whereas the non-US subgroup showed significant reductions in the primary and key secondary end points, the US subgroup demonstrated particularly robust risk reductions across a variety of individual and composite end points, including all-cause mortality.
CLINICAL TRIAL REGISTRATION
URL: https://www.clinicaltrials.gov. Unique identifier: NCT01492361.
背景
一些试验发现，来自美国的患者获益不如美国以外地区入组的患者。本预先设定的 REDUCE-IT（依泽替米贝降低心血管事件试验）亚组分析旨在确定依泽替米贝在美国的获益程度。
方法
RE-DUCE-IT 试验将 8179 名接受他汀类药物治疗且符合甘油三酯≥135 且＜500mg/dL 和低密度脂蛋白胆固醇＞40 且≤100mg/dL 且有动脉粥样硬化或糖尿病史的患者随机分为依泽替米贝 4g/d 组或安慰剂组。主要复合终点是心血管死亡、非致死性心肌梗死、非致死性卒中和冠状动脉血运重建或不稳定型心绞痛住院。预先设定了一个层次结构来检查个体和复合终点。
结果
共有 3146 名美国患者（试验的 38.5%）被随机分组并随访中位数为 4.9 年；32.3%为女性，9.7%为西班牙裔。安慰剂组的主要复合终点发生率为 24.7%，依泽替米贝组为 18.2%（风险比[HR]，0.69[95%CI，0.59-0.80]；=0.000001）；关键次要复合终点发生率为 16.6%与 12.1%（HR，0.69[95%CI，0.57-0.83]；=0.00008）。所有预先设定的分层终点均有意义且显著降低，包括心血管死亡（6.7%降至 4.7%；HR，0.66[95%CI，0.49-0.90]；=0.007）、心肌梗死（8.8%降至 6.7%；HR，0.72[95%CI，0.56-0.93]；=0.01）、卒中和全因死亡率（4.1%降至 2.6%；HR，0.63[95%CI，0.43-0.93]；=0.02）；美国患者全因死亡率与非美国患者相比，=0.02。安全性和耐受性结果与整个研究队列一致。
结论
尽管非美国亚组主要和关键次要终点显著降低，但美国亚组在各种个体和复合终点均显示出特别显著的风险降低，包括全因死亡率。
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