PCSK9 inhibitor combination with statins improves functional independence and reduces recurrence in ischemic strokeAdding PCSK9 inhibitors to statins may help stroke recovery

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 I 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, I = 48%) and reduced recurrent ischemic stroke risk (OR = 0.33, 95% CI 0.16-0.69, P = 0.003, I = 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 (I = 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, I = 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.