Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
State University of New York, Downstate School of Public Health, Brooklyn, New York.
J Am Coll Cardiol. 2019 Sep 3;74(9):1167-1176. doi: 10.1016/j.jacc.2019.03.013. Epub 2019 Mar 18.
Patients with acute coronary syndrome (ACS) and concomitant noncoronary atherosclerosis have a high risk of major adverse cardiovascular events (MACEs) and death. The impact of lipid lowering by proprotein convertase subtilisin-kexin type 9 inhibition in such patients is undetermined.
This pre-specified analysis from ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) determined whether polyvascular disease influenced risks of MACEs and death and their modification by alirocumab in patients with recent ACS and dyslipidemia despite intensive statin therapy.
Patients were randomized to alirocumab or placebo 1 to 12 months after ACS. The primary MACEs endpoint was the composite of coronary heart disease death, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization. All-cause death was a secondary endpoint.
Median follow-up was 2.8 years. Of 18,924 patients, 17,370 had monovascular (coronary) disease, 1,405 had polyvascular disease in 2 beds (coronary and peripheral artery or cerebrovascular), and 149 had polyvascular disease in 3 beds (coronary, peripheral artery, cerebrovascular). With placebo, the incidence of MACEs by respective vascular categories was 10.0%, 22.2%, and 39.7%. With alirocumab, the corresponding absolute risk reduction was 1.4% (95% confidence interval [CI]: 0.6% to 2.3%), 1.9% (95% CI: -2.4% to 6.2%), and 13.0% (95% CI: -2.0% to 28.0%). With placebo, the incidence of death by respective vascular categories was 3.5%, 10.0%, and 21.8%; the absolute risk reduction with alirocumab was 0.4% (95% CI: -0.1% to 1.0%), 1.3% (95% CI: -1.8% to 4.3%), and 16.2% (95% CI: 5.5% to 26.8%).
In patients with recent ACS and dyslipidemia despite intensive statin therapy, polyvascular disease is associated with high risks of MACEs and death. The large absolute reductions in those risks with alirocumab are a potential benefit for these patients. (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab [ODYSSEY OUTCOMES]: NCT01663402).
患有急性冠状动脉综合征（ACS）和同时存在非冠状动脉粥样硬化的患者有发生主要不良心血管事件（MACE）和死亡的高风险。在这些患者中，前蛋白转化酶枯草溶菌素/激肽释放酶 9 抑制剂降低血脂的影响尚不确定。
这是 ODYSSEY OUTCOMES（急性冠状动脉综合征治疗期间依洛尤单抗对心血管结局的评估）的一项预先指定分析，旨在确定多血管疾病是否会影响近期 ACS 和他汀类药物强化治疗后血脂异常患者的 MACE 和死亡风险，以及依洛尤单抗对这些风险的影响。
患者在 ACS 后 1 至 12 个月随机分配至依洛尤单抗或安慰剂组。主要 MACE 终点是冠心病死亡、非致死性心肌梗死、致死性或非致死性缺血性卒中和需要住院治疗的不稳定型心绞痛的复合终点。全因死亡是次要终点。
中位随访时间为 2.8 年。在 18924 例患者中，17370 例为单血管（冠状动脉）疾病，1405 例为 2 个部位（冠状动脉和外周动脉或脑血管）的多血管疾病，149 例为 3 个部位（冠状动脉、外周动脉、脑血管）的多血管疾病。在接受安慰剂治疗的患者中，相应血管类别的 MACE 发生率分别为 10.0%、22.2%和 39.7%。依洛尤单抗治疗的相应绝对风险降低分别为 1.4%（95%CI：0.6%至 2.3%）、1.9%（95%CI：-2.4%至 6.2%）和 13.0%（95%CI：-2.0%至 28.0%）。在接受安慰剂治疗的患者中，相应血管类别的死亡率分别为 3.5%、10.0%和 21.8%；依洛尤单抗治疗的绝对风险降低分别为 0.4%（95%CI：-0.1%至 1.0%）、1.3%（95%CI：-1.8%至 4.3%）和 16.2%（95%CI：5.5%至 26.8%）。
在近期 ACS 和他汀类药物强化治疗后仍存在血脂异常的患者中，多血管疾病与 MACE 和死亡的高风险相关。依洛尤单抗可显著降低这些风险，这可能使这些患者受益。（急性冠状动脉综合征治疗期间依洛尤单抗对心血管结局的评估[ODYSSEY OUTCOMES]：NCT01663402）。
