Department of Cardiology, The Sixth People's Hospital of Chengdu, Chengdu 610000, China.
Department of Cardiac Ultrasound, Peking Union Medical College Hospital, Beijing 100005, China.
Medicine (Baltimore). 2024 Mar 8;103(10):e37416. doi: 10.1097/MD.0000000000037416.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to be effective and safe in patients with stable angina and previous myocardial infarction. However, evidence for initiating their use in patients hospitalized with acute coronary syndrome (ACS) is limited. This systematic review and meta-analysis was performed to provide more clinical evidence.
PubMed, Embase, OVID, Cochrane Library and ClinicalTrials.gov were systematically searched for eligible randomized controlled trials up to March 20, 2023. The risk ratios, standardized mean differences and 95% confidence intervals were calculated for primary and secondary outcomes. The bias risk of the included studies was assessed using the Cochrane RoB 2 criteria.
About 8 randomized controlled trials involving 1255 inpatients with ACS were included. PCSK9 inhibitor treatment significantly reduced low-density lipoprotein cholesterol (LDL-C) (SMD -1.28, 95% CI -1.76 to -0.8, P = .001), triglycerides (TG) (SMD -0.93, 95% CI -1.82 to -0.05, P = .03), total cholesterol (SMD -1.36, 95% CI -2.01 to -0.71, P = .001), and apolipoprotein B (Apo B) (SMD -0.81, 95% CI -1.09 to -0.52, P = .001) within approximately 1 month. PCSK9 inhibitor treatment significantly reduced the total atheroma volume (TAV) (SMD -0.33, 95% CI -0.59 to -0.07, P = .012). It also significantly increased minimum fibrous cap thickness (FCT) (SMD 0.41, 95% CI 0.22-0.59, P = .001) in long-term follow-up (>6 months). PCSK9 inhibitor treatment significantly reduced the risk of readmission for unstable angina (RR 0.32, 95% CI 0.12-0.91, P = .032) in short-term follow-up (<6 months). There were no significant differences in all-cause mortality, cardiovascular death, myocardial infarction, ischemic stroke, coronary revascularization or heart failure. Only nasopharyngitis (RR 1.71, 95% CI 1.01-2.91, P = .047) adverse events were significantly observed in the PCSK9 inhibitor group.
Application of a PCSK9 inhibitor in hospitalized patients with ACS reduced lipid profiles and plaque burdens and was well tolerated with few adverse events.
前蛋白转化酶枯草溶菌素 9（PCSK9）抑制剂已被证明在稳定型心绞痛和心肌梗死患者中安全有效。然而，关于在急性冠状动脉综合征（ACS）住院患者中启动其使用的证据有限。本系统评价和荟萃分析旨在提供更多的临床证据。
系统检索 PubMed、Embase、OVID、Cochrane 图书馆和 ClinicalTrials.gov 截至 2023 年 3 月 20 日的合格随机对照试验。计算主要和次要结局的风险比、标准化均数差和 95%置信区间。使用 Cochrane RoB 2 标准评估纳入研究的偏倚风险。
共纳入 8 项涉及 1255 例 ACS 住院患者的随机对照试验。PCSK9 抑制剂治疗可显著降低低密度脂蛋白胆固醇（LDL-C）（SMD-1.28，95%CI-1.76 至-0.8，P=0.001）、甘油三酯（TG）（SMD-0.93，95%CI-1.82 至-0.05，P=0.03）、总胆固醇（SMD-1.36，95%CI-2.01 至-0.71，P=0.001）和载脂蛋白 B（Apo B）（SMD-0.81，95%CI-1.09 至-0.52，P=0.001），治疗后约 1 个月。PCSK9 抑制剂治疗可显著降低总动脉粥样硬化体积（TAV）（SMD-0.33，95%CI-0.59 至-0.07，P=0.012）。在长期随访（>6 个月）中，它还显著增加了最小纤维帽厚度（FCT）（SMD 0.41，95%CI 0.22-0.59，P=0.001）。在短期随访（<6 个月）中，PCSK9 抑制剂治疗可显著降低不稳定型心绞痛再入院风险（RR 0.32，95%CI 0.12-0.91，P=0.032）。全因死亡率、心血管死亡率、心肌梗死、缺血性卒中和冠状动脉血运重建或心力衰竭均无显著差异。仅观察到 PCSK9 抑制剂组的鼻咽部炎症（RR 1.71，95%CI 1.01-2.91，P=0.047）不良事件显著增加。
PCSK9 抑制剂在 ACS 住院患者中的应用可降低血脂谱和斑块负担，且耐受性良好，不良事件较少。
