PCSK9抑制剂联合他汀类药物治疗急性缺血性卒中的疗效与安全性：一项系统评价与荟萃分析。
完整摘要 · 中文译文
背景：急性缺血性卒中（AIS）在全球范围内造成显著的死亡和长期残疾负担。作为新型调脂药物，前蛋白转化酶枯草溶菌素/kexin 9型抑制剂（PCSK9i）已在广泛的心血管患者群体中显示出治疗获益，但在AIS队列中的专门证据尚未进行定量综合。因此，我们开展了这项meta分析，以比较PCSK9i联合他汀治疗与单用他汀治疗在AIS患者中的疗效和安全性。 方法：我们检索了7个数据库，从建库至2026年5月31日，纳入随机对照试验（RCT）。两名评价者独立进行研究筛选、数据提取和偏倚风险评估。二分类结局和连续型结局分别采用比值比（OR）和均数差（MD）进行合并。通过I2统计量和Cochran's Q检验评估异质性，并采用逐一剔除敏感性分析和模型切换来探究异质性并检验稳健性。我们采用GRADE方法评价证据确定性。 结果：与单用他汀治疗相比，PCSK9i联合治疗显著改善了功能独立（改良Rankin量表（mRS）0-2：OR = 2.17，95% CI 1.29-3.64，P = 0.003，I2 = 48%），并降低了复发性缺血性卒中风险（OR = 0.33，95% CI 0.16-0.69，P = 0.003，I2 = 0%）。联合治疗组LDL-C显著降低（MD = 0.66 mmol/L，95% CI 0.45-0.87，P < 0.00001），高异质性（I2 = 86%）部分可由他汀类型（阿托 他汀与瑞舒伐他汀比较，P = 0.02）。美国国立卫生研究院卒中量表（NIHSS）评分未见显著差异（MD = 2.38，95% CI - 0.63 至 5.39，P = 0.12，I2 = 98%），异质性主要由一项研究驱动。安全性结局，包括肝功能异常（OR = 0.67，95% CI 0.35-1.28，P = 0.22）、主要不良心血管事件（MACE）（OR = 0.56，95% CI 0.18-1.75，P = 0.32）和总不良事件（OR = 0.85，95% CI 0.49-1.45，P = 0.54），在组间具有可比性。根据GRADE评估，mRS的证据确定性为中等，复发性卒中、LDL-C和安全性结局为低，NIHSS为极低。 结论：PCSK9i辅助治疗可能改善接受他汀治疗的AIS患者的功能恢复并减少卒中复发，短期安全性可接受；然而，当前证据仍属初步，需要在更大规模、把握度充分的随机试验中加以确认。
完整摘要 · 英文原文
BACKGROUND: Acute ischemic stroke (AIS) imposes a substantial global burden of mortality and long-term disability. As novel lipid-modulating agents, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) have demonstrated therapeutic benefits across a wide range of cardiovascular patient groups, but dedicated evidence in AIS cohorts has not been quantitatively synthesized. We therefore conducted this meta-analysis to compare the efficacy and safety of PCSK9i combined with statin therapy versus statin monotherapy among patients with AIS. METHODS: We searched seven databases from inception to May 31, 2026 for randomized controlled trials (RCTs). Two reviewers independently performed study screening, data extraction, and risk-of-bias assessment. Dichotomous and continuous outcomes were synthesized using odds ratios (OR) and mean differences (MD), respectively. Heterogeneity was assessed via the I2 statistic and Cochran's Q test, with leave-one-out sensitivity analysis and model switching to explore heterogeneity and test robustness. We evaluated the certainty of evidence using the GRADE approach. RESULTS: Compared with statin monotherapy, PCSK9i combination therapy significantly improved functional independence (modified Rankin Scale (mRS) 0-2: OR = 2.17, 95% CI 1.29-3.64, P = 0.003, I2 = 48%) and reduced recurrent ischemic stroke risk (OR = 0.33, 95% CI 0.16-0.69, P = 0.003, I2 = 0%). LDL-C was substantially reduced in the combination group (MD = 0.66 mmol/L, 95% CI 0.45-0.87, P < 0.00001), with high heterogeneity (I2 = 86%) partially explained by statin type (atorvastatin vs. rosuvastatin, P = 0.02). No significant difference was observed in National Institutes of Health Stroke Scale (NIHSS) scores (MD = 2.38, 95% CI - 0.63 to 5.39, P = 0.12, I2 = 98%), with heterogeneity largely driven by one study. Safety outcomes, including abnormal liver function (OR = 0.67, 95% CI 0.35-1.28, P = 0.22), major adverse cardiovascular events(MACE) (OR = 0.56, 95% CI 0.18-1.75, P = 0.32), and total adverse events (OR = 0.85, 95% CI 0.49-1.45, P = 0.54), were comparable between groups. According to the GRADE assessment, evidence certainty was moderate for mRS, low for recurrent stroke, LDL-C, and safety outcomes, and very low for NIHSS. CONCLUSIONS: PCSK9i adjunctive therapy may improve functional recovery and reduce stroke recurrence in AIS patients receiving statins, with acceptable short-term safety; however, the current evidence remains preliminary and requires confirmation in larger, adequately powered randomized trials.