Long-Term Evolocumab in Patients With Established Atherosclerotic Cardiovascular Disease
Long-Term Evolocumab in Patients With Established Atherosclerotic Cardiovascular Disease
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DOI：
10.1161/circulationaha.122.061620
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发表时间：
2022-10-11
期刊：
影响因子：
37.8
通讯作者：
Sabatine, Marc S.
中科院分区：
文献类型：
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作者：
O'Donoghue, Michelle L.;Giugliano, Robert P.;Sabatine, Marc S.
背景资料：在FOURIER（在高风险受试者中进行PCSK 9抑制的进一步心血管结局研究）中，前蛋白转化酶枯草杆菌蛋白酶-kexin 9型抑制剂evoloclavin降低了低密度脂蛋白胆固醇（LDL-C）和心血管事件的风险，并且在中位2.2年的随访中安全且耐受性良好。然而，缺乏大规模、长期的数据。方法：FOURIER母试验将27564名患有动脉粥样硬化性心血管疾病且LDL-C >= 70 mg/dL的患者随机分配，接受他汀类药物治疗，并接受依洛尤单抗与安慰剂治疗。在参与研究中心完成FOURIER的患者有资格在美国和欧洲的2项开放标签扩展研究（FOURIER-OLE [FOURIER开放标签扩展]）中接受依洛尤单抗治疗;主要分析在研究间汇总。主要终点是不良事件的发生率。血脂值和主要不良心血管事件进行了前瞻性collected.Results：共6635例患者参加了FOURIER-OLE（3355随机evolocumab和3280安慰剂在母研究）。FOURIER-OLE的中位随访时间为5.0年;父母联合FOURIER-OLE的依洛尤单抗最大暴露时间为8.4年。在FOURIER-OLE中，第12周时，LDL-C中位数为30 mg/dL，63.2%的患者达到LDL-C 8年，未超过母研究期间在原始安慰剂组中观察到的水平，并且与延迟治疗开始相比，导致心血管事件进一步减少。注册：URL：;唯一标识符：NCT 02867813和NCT 03080935。
Background: In FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk), the proprotein convertase subtilisin-kexin type 9 inhibitor evolocumab reduced low-density lipoprotein cholesterol (LDL-C) and risk of cardiovascular events and was safe and well tolerated over a median of 2.2 years of follow-up. However, large-scale, long-term data are lacking.Methods: The parent FOURIER trial randomized 27 564 patients with atherosclerotic cardiovascular disease and LDL-C >= 70 mg/dL on statin to evolocumab versus placebo. Patients completing FOURIER at participating sites were eligible to receive evolocumab in 2 open-label extension studies (FOURIER-OLE [FOURIER Open-Label Extension]) in the United States and Europe; primary analyses were pooled across studies. The primary end point was the incidence of adverse events. Lipid values and major adverse cardiovascular events were prospectively collected.Results: A total of 6635 patients were enrolled in FOURIER-OLE (3355 randomized to evolocumab and 3280 to placebo in the parent study). Median follow-up in FOURIER-OLE was 5.0 years; maximum exposure to evolocumab in parent plus FOURIER-OLE was 8.4 years. At 12 weeks in FOURIER-OLE, median LDL-C was 30 mg/dL, and 63.2% of patients achieved LDL-C 8 years that did not exceed those observed in the original placebo arm during the parent study and led to further reductions in cardiovascular events compared with delayed treatment initiation.Registration: URL: ; Unique identifiers: NCT02867813 and NCT03080935.