Clinical Outcomes of Early Administration of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors in East Asian Patients with Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

Background

Dyslipidemia is a modifiable risk factor and predictive biomarker for acute ischemic stroke (AIS) that necessitates early, aggressive lipid-lowering therapy to achieve target low-density lipoprotein cholesterol (LDL-C) levels for primary and secondary prevention. In certain patients, this can be difficult to achieve with statins alone. Proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) lipid-lowering agents may improve outcomes when introduced early. This review assessed whether early PCSK9i administration (within 3 weeks of AIS) reduced early neurological deterioration (END), recurrent stroke/transient ischemic attack (TIA), poor functional outcomes, and mortality.

Methods

This systematic review and meta-analysis included randomized clinical trials (RCTs) and observational studies. Random-effects meta-analysis and subgroup and sensitivity analyses were used to assess whether effects differed by treatment timing (≤72 vs. >72 h) and study design.

Results

Eight studies (three randomized clinical trials) in East Asian cohorts were included. Early PCSK9i initiation significantly reduced END compared with usual care (odds ratio [OR]: 0.39; 95% confidence interval [CI]: 0.26-0.57). Stroke/TIA recurrence and all-cause mortality within 6 months of stroke were also significantly reduced in the PCSK9i group (OR: 0.47; 95% CI: 0.28-0.77 and OR: 0.33; 95% CI: 0.15-0.72, respectively), and early initiation was associated with a greater likelihood of good functional outcomes at 90 days (OR: 2.28; 95% CI: 1.48-3.51). Sensitivity analyses yielded consistent results.

Conclusions

Early PCSK9i initiation within 3 weeks of AIS onset was associated with lower rates of END, recurrent stroke/TIA, and mortality, although the certainty of evidence was limited by the small number of included studies and the predominantly observational data. Outcomes did not differ significantly by initiation timing within this period. Large-scale trials in diverse populations are needed to define the optimal initiation window and long-term clinical effects.