Efficacy and safety of PCSK9 inhibitors combined with statins in acute ischemic stroke: a systematic review and meta-analysis
In brief
Adding PCSK9 drugs more than doubled odds of independence after stroke
In pooled trials of people with acute ischemic stroke, adding a PCSK9 inhibitor to a statin was associated with more than twice the odds of functional independence and about two-thirds fewer recurrent strokes than statin alone. Short-term adverse events were similar, but evidence for recurrence and safety was low certainty, so larger trials are needed to confirm the benefits.
- Journal
- Journal of neurology (Q1)
- Published
- 8 October 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Xiaozuo Lin, Rongxin He, Xiaohan Zhang, Yinan Zeng, Tian Wang, Simin Chen, et al.
- PMID
- 42848227
- DOI
- 10.1007/s00415-026-14199-w
Why clinicians should know about it
- Picked for Neurology (clinical) (top studies of the week, 11 October 2026): PCSK9 inhibitors plus statins in acute ischemic stroke – meta‑analysis
Abstract
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.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.