Risk Categorization Using New American College of Cardiology/American Heart Association Guidelines for Cholesterol Management and Its Relation to Alirocumab Treatment Following Acute Coronary Syndromes
Risk Categorization Using New American College of Cardiology/American Heart Association Guidelines for Cholesterol Management and Its Relation to Alirocumab Treatment Following Acute Coronary Syndromes
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DOI：
10.1161/circulationaha.119.042551
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发表时间：
2019-11-05
期刊：
影响因子：
37.8
通讯作者：
Zobouyan, Isabelle
中科院分区：
文献类型：
--
作者：
Roe, Matthew T.;Li, Qian H.;Zobouyan, Isabelle
背景资料：2018年美国胆固醇管理指南建议，尽管接受了最大耐受他汀类药物治疗，但低密度脂蛋白胆固醇>= 70 mg/dL或非高密度脂蛋白胆固醇>= 100 mg/dL的患者仍应额外接受降脂治疗作为二级预防。基于>1次主要动脉粥样硬化性心血管疾病（ASCVD）事件或单一ASCVD事件和多种高风险状况的病史，此类患者被认为处于极高风险（VHR）。我们研究了美国指南定义的风险类别与急性冠状动脉综合征后缺血性事件发生的相关性，以及alirocumab（一种PCSK 9（前蛋白转化酶枯草杆菌蛋白酶/kexin 9型）抑制剂）减少这些事件的作用。研究方法：在ODYSSEY OUTCOMES试验（Alirocumab治疗期间急性冠状动脉综合征后的心血管结局评价）中，尽管接受了最佳他汀类药物治疗，但近期发生急性冠状动脉综合征和残留血脂异常的患者被随机分配至alirocumab组或安慰剂组。根据美国心脏病学会/美国心脏协会风险分类检查主要试验结局（主要不良心血管事件，即冠心病死亡、非致死性心肌梗死、缺血性卒中或因不稳定型心绞痛住院）。结果如下：在18924例受试者中，11935例（63.1%）被归类为VHR：4450例（37.3%）既往发生过多次ASCVD事件，7485例（62.7%）发生过1起主要ASCVD事件和多种高危疾病。VHR时安慰剂治疗患者的主要不良心血管事件发生率为14.4%，而非VHR时为5.6%。在VHR类别中，20.4%的既往发生过多次ASCVD事件的患者发生了重大心血管不良事件，而10.7%的既往发生过1次ASCVD事件和多种高风险疾病的患者发生了重大心血管不良事件。Alibaba与两种风险类别（VHR风险比=0.84;非VHR风险比=0.86; P-相互作用=0.820）和VHR组内分层（多起既往ASCVD事件风险比=0.86; 1起主要ASCVD事件和多种高风险疾病风险比=0.82; P-相互作用=0.672）的一致相对风险降低相关。在VHR组中，alirocumab组主要心血管不良事件的绝对风险降低在数值上大于（但无统计学差异）未接受VHR的患者（2.1% vs 0.8%; P-相互作用=0.095），在接受VHR且既往发生过多次ASCVD事件的患者中，alirocumab组主要心血管不良事件的绝对风险降低在数值上大于既往发生过1次ASCVD事件的患者（2.4% vs 1.8%; P-相互作用=0.661）。结论：美国指南标准确定了近期急性冠脉综合征和血脂异常患者，这些患者因复发性缺血事件处于VHR，并且可能从alirocumab治疗中获得更大的绝对获益。
Background: The 2018 US cholesterol management guidelines recommend additional lipid-lowering therapies for secondary prevention in patients with low-density lipoprotein cholesterol >= 70 mg/dL or non-high-density lipoprotein cholesterol >= 100 mg/dL despite maximum tolerated statin therapy. Such patients are considered at very high risk (VHR) based on a history of >1 major atherosclerotic cardiovascular disease (ASCVD) event or a single ASCVD event and multiple high-risk conditions. We investigated the association of US guideline-defined risk categories with the occurrence of ischemic events after acute coronary syndrome and reduction of those events by alirocumab, a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor. Methods: In the ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab), patients with recent acute coronary syndrome and residual dyslipidemia despite optimal statin therapy were randomly assigned to alirocumab or placebo. The primary trial outcome (major adverse cardiovascular events, ie, coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or hospitalization for unstable angina) was examined according to American College of Cardiology/American Heart Association risk category. Results: Of 18 924 participants followed for a median of 2.8 years, 11 935 (63.1%) were classified as VHR: 4450 (37.3%) had multiple prior ASCVD events and 7485 (62.7%) had 1 major ASCVD event and multiple high-risk conditions. Major adverse cardiovascular events occurred in 14.4% of placebo-treated patients at VHR versus 5.6% of those not at VHR. In the VHR category, major adverse cardiovascular events occurred in 20.4% with multiple prior ASCVD events versus 10.7% with 1 ASCVD event and multiple high-risk conditions. Alirocumab was associated with consistent relative risk reductions in both risk categories (hazard ratio=0.84 for VHR; hazard ratio=0.86 for not VHR; P-interaction=0.820) and by stratification within the VHR group (hazard ratio=0.86 for multiple prior ASCVD events; hazard ratio=0.82 for 1 major ASCVD event and multiple high-risk conditions; P-interaction=0.672). The absolute risk reduction for major adverse cardiovascular events with alirocumab was numerically greater (but not statistically different) in the VHR group versus those not at VHR (2.1% versus 0.8%; P-interaction=0.095) and among patients at VHR with multiple prior ASCVD events versus a single prior ASCVD event (2.4% versus 1.8%; P-interaction=0.661). Conclusions: The US guideline criteria identify patients with recent acute coronary syndrome and dyslipidemia who are at VHR for recurrent ischemic events and who may derive a larger absolute benefit from treatment with alirocumab.