Estudios Clínicos Latino América, Instituto Cardiovascular de Rosario, Argentina.
Regeneron Pharmaceuticals Inc., Tarrytown, USA.
Eur J Prev Cardiol. 2021 Mar 23;28(1):33-43. doi: 10.1177/2047487320941987. Epub 2020 Jul 27.
Statins are pivotal to the secondary prevention of major adverse cardiovascular events, but some patients are statin-intolerant. We examined the effects of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor alirocumab on the risk of major adverse cardiovascular events according to the intensity of background statin treatment.
The ODYSSEY OUTCOMES trial compared alirocumab with placebo in 18,924 patients with acute coronary syndrome and dyslipidaemia despite intensive or maximum-tolerated statin treatment (including no statin if intolerance was documented). The primary outcome (major adverse cardiovascular events) comprised coronary heart disease death, non-fatal myocardial infarction, ischaemic stroke, or unstable angina. Median follow-up was 2.8 years. Baseline statin treatment was high-intensity (88.8%), low/moderate-intensity (8.7%) or none (2.4%). Median baseline low-density lipoprotein cholesterol was 86, 89 and 139 mg/dL (P < 0.001) in these statin treatment categories, respectively. Alirocumab produced similar relative reductions in low-density lipoprotein cholesterol from baseline across statin treatment subgroups, but the mean absolute reductions differed (52.9, 56.7 and 86.1 mg/dL, respectively; P < 0.001). With placebo, the incidence of major adverse cardiovascular events was highest in the no statin subgroup (10.8%, 10.7% and 26.0% respectively). Alirocumab reduced major adverse cardiovascular events in each statin subgroup (hazard ratio 0.88, 95% confidence interval (CI) 0.80-0.96; 0.68, 0.49-0.94; and 0.65, 0.44-0.97, respectively; Pinteraction = 0.14) with a gradient of absolute risk reduction: 1.25%, 95% CI 0.34-2.16; 3.16%, 0.38-5.94; 7.97%, 0.42-15.51; Pinteraction = 0.106).
PCSK9 inhibition with alirocumab reduces the relative risk of major adverse cardiovascular events after acute coronary syndrome irrespective of background statin treatment. However, patients on no statin are at high absolute risk for recurrent major adverse cardiovascular events; alirocumab substantially reduces that risk. PCSK9 inhibition may be an important therapeutic strategy for statin-intolerant patients with acute coronary syndrome.
他汀类药物是预防主要不良心血管事件的关键，但有些患者对他汀类药物不耐受。我们研究了前蛋白转化酶枯草溶菌素/克那霉 9（PCSK9）抑制剂阿利西尤单抗在强化背景他汀类药物治疗的基础上，对主要不良心血管事件风险的影响，按背景他汀类药物治疗强度进行分层。
ODYSSEY OUTCOMES 试验将阿利西尤单抗与安慰剂在 18924 例急性冠脉综合征和血脂异常患者中进行了比较，这些患者尽管接受了强化或最大耐受他汀类药物治疗（如果不耐受记录，则不使用他汀类药物）。主要终点（主要不良心血管事件）包括冠心病死亡、非致死性心肌梗死、缺血性卒中和不稳定型心绞痛。中位随访时间为 2.8 年。基线他汀类药物治疗强度为高强度（88.8%）、低/中强度（8.7%）或无（2.4%）。这些他汀类药物治疗亚组的基线低密度脂蛋白胆固醇中位数分别为 86、89 和 139mg/dL（P<0.001）。阿利西尤单抗在他汀类药物治疗亚组中均能使低密度脂蛋白胆固醇从基线水平产生相似的相对降低，但平均绝对降低程度不同（分别为 52.9、56.7 和 86.1mg/dL；P<0.001）。在安慰剂组中，无他汀类药物亚组的主要不良心血管事件发生率最高（分别为 10.8%、10.7%和 26.0%）。阿利西尤单抗降低了每个他汀类药物治疗亚组的主要不良心血管事件风险（风险比 0.88，95%置信区间 0.80-0.96；0.68，0.49-0.94；0.65，0.44-0.97；P 交互=0.14），绝对风险降低梯度为：1.25%，95%置信区间 0.34-2.16%；3.16%，0.38-5.94%；7.97%，0.42-15.51%；P 交互=0.106）。
急性冠脉综合征患者应用阿利西尤单抗抑制 PCSK9 可降低主要不良心血管事件的相对风险，而不论其背景他汀类药物治疗如何。然而，不使用他汀类药物的患者发生主要不良心血管事件的绝对风险较高；阿利西尤单抗显著降低了这种风险。PCSK9 抑制可能是急性冠脉综合征他汀类药物不耐受患者的重要治疗策略。
