TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, 60 Fenwood Road, Suite 7022, Boston, MA 02115, USA.
Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
Eur Heart J. 2021 Dec 14;42(47):4821-4829. doi: 10.1093/eurheartj/ehab604.
We assessed the impact of the proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor evolocumab on acute arterial events across all vascular territories, including coronary, cerebrovascular, and peripheral vascular beds, in patients with established atherosclerotic cardiovascular disease (ASCVD).
In the FOURIER trial, 27 564 patients with stable ASCVD on statin therapy were randomly assigned to evolocumab or placebo. Acute arterial events were a composite of acute coronary (coronary heart disease death, myocardial infarction, or urgent coronary revascularization), cerebrovascular (ischaemic stroke, transient ischaemic attack, or urgent cerebral revascularization), or peripheral vascular (acute limb ischaemia, major amputation, or urgent peripheral revascularization) events. Of the 2210 first acute arterial events, 74% were coronary, 22% were cerebrovascular, and 4% were peripheral vascular. Evolocumab reduced first acute arterial events by 19% (hazard ratio [HR] 0.81 [95% confidence interval 0.74-0.88]; P < 0.001), with significant individual reductions in acute coronary (HR 0.83 [0.75-0.91]), cerebrovascular (HR 0.77 [0.65-0.92]), and peripheral vascular (HR 0.58 [0.38-0.88]) events. There were 3437 total events (first plus recurrent), with evolocumab reducing total events by 24% (incidence rate ratio 0.76 [0.69-0.85]). The magnitude of reduction in acute arterial events with evolocumab numerically increased over time, with a 16% reduction (HR 0.84 [0.75-0.95]) in the first year followed by a 24% reduction (HR 0.76 [0.67-0.85]) thereafter.
The addition of the PCSK9 inhibitor evolocumab to statin therapy reduced acute arterial events across all vascular territories with a robust effect over time, indicating a pan-vascular impact of aggressive lipid-lowering therapy on these acute and clinically meaningful events.
URL: https://www.clinicaltrials.gov. Unique identifier: NCT01764633.
我们评估了前蛋白转化酶枯草溶菌素 9（PCSK9）抑制剂依洛尤单抗对已确诊动脉粥样硬化性心血管疾病（ASCVD）患者所有血管床（包括冠状动脉、脑血管和外周血管床）急性动脉事件的影响。
在 FOURIER 试验中，27564 名正在接受他汀类药物治疗的稳定 ASCVD 患者被随机分配至依洛尤单抗或安慰剂组。急性动脉事件是由急性冠状动脉事件（冠心病死亡、心肌梗死或紧急冠状动脉血运重建）、脑血管事件（缺血性卒中和短暂性脑缺血发作或紧急脑血运重建）或外周血管事件（急性肢体缺血、大截肢或紧急外周血运重建）复合而成。在 2210 例首次急性动脉事件中，74%为冠状动脉事件，22%为脑血管事件，4%为外周血管事件。依洛尤单抗使首次急性动脉事件减少 19%（风险比 [HR]0.81[95%置信区间 0.74-0.88]；P<0.001），急性冠状动脉（HR0.83[0.75-0.91]）、脑血管（HR0.77[0.65-0.92]）和外周血管（HR0.58[0.38-0.88]）事件的发生率显著降低。共发生 3437 例总事件（首发和复发），依洛尤单抗使总事件减少 24%（发生率比 0.76[0.69-0.85]）。依洛尤单抗降低急性动脉事件的幅度随时间增加，第 1 年减少 16%（HR0.84[0.75-0.95]），此后减少 24%（HR0.76[0.67-0.85]）。
在他汀类药物治疗的基础上加用 PCSK9 抑制剂依洛尤单抗可减少所有血管床的急性动脉事件，且随着时间的推移效果显著，表明强化降脂治疗对这些急性和有临床意义的事件具有广泛的血管影响。
