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Background <p>Acute ischemic stroke (AIS) carries high risks of recurrence, disability, and death despite standard therapy. The role of Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors has been shown to provide cardiovascular benefits, but their role in the acute neurovascular phase of AIS remains uncertain.</p> Methods <p>We systematically searched PubMed, MEDLINE, Embase, Web of Science, and the Cochrane Library from inception to August 31, 2025, for studies initiating PCSK9 inhibitors during hospitalization or within 14 days of AIS symptom onset. Primary outcomes were early recurrent stroke/transient ischemic attack (TIA) within 30 days, early neurological deterioration (END) within 7 days, and functional independence (modified Rankin Scale [mRS] ≤ 2 at 90 days). Pooled risk ratios (RRs) and mean differences (MDs) were calculated using fixed-effect models when statistical heterogeneity was low (I² ≤50%) and random-effects models when heterogeneity was substantial (I² &gt;50%). This review was prospectively registered in PROSPERO (CRD420251144202).</p> Results <p>Five studies (<i>n</i> = 1,842) met eligibility criteria. Early PCSK9 inhibitor use was associated with a lower risk of recurrent stroke/TIA (5 studies, <i>n</i> = 1,842; RR 0.38, 95% CI 0.26–0.54; I²=45.5%; low certainty), all cause mortality (3 studies, <i>n</i> = 1,061; RR 0.48, 95% CI 0.30–0.77; I²=0%; low certainty), and early neurological deterioration (2 studies, <i>n</i> = 533; RR 0.56, 95% CI 0.36–0.88; I²=0%; low certainty), and was associated with a higher likelihood of functional independence (mRS ≤ 2 at 90 days) (2 studies, <i>n</i> = 533; RR 1.31, 95% CI 1.15– 1.50; I²=0%; very low certainty). LDLC was significantly reduced (5 studies, <i>n</i> = 1,842; MD − 0.91 mmol/L, 95% CI − 1.26 to − 0.57; I²=93%; very low certainty). The certainty of evidence was downgraded primarily due to the risk of bias in included studies and imprecision.</p> Conclusions <p>Early initiation of PCSK9 inhibitors after AIS was associated with a higher likelihood of favorable short-term clinical outcomes and substantial LDL-C reduction. These findings suggest that PCSK9 inhibitors may confer neurovascular benefits, warranting confirmation in larger trials.</p>

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Impact of early use of PCSK9 inhibitors in acute ischemic stroke: a systematic review and meta-analysis

  • 期刊论文

  • 发表日期：

    2026年3月26日

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  • Khadeeja Ali Hamzah,
  • Yousif Hameed Kurmasha,
  • Mohammedsadeq A. Shweliya,
  • Ali Saad Al-Shammari,
  • Khalid Radwan Alsaadany,
  • Abdallah Adel Nofal,
  • Abdullah Muataz Taha Al-Ibraheem,
  • Ahmed Sermed Al Sakini,
  • Nihar Jena,
  • Sharmeen Naz,
  • Moinuddin Syed,
  • Melaku Demede,
  • Yasar Sattar

摘要

Background

Acute ischemic stroke (AIS) carries high risks of recurrence, disability, and death despite standard therapy. The role of Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors has been shown to provide cardiovascular benefits, but their role in the acute neurovascular phase of AIS remains uncertain.

Methods

We systematically searched PubMed, MEDLINE, Embase, Web of Science, and the Cochrane Library from inception to August 31, 2025, for studies initiating PCSK9 inhibitors during hospitalization or within 14 days of AIS symptom onset. Primary outcomes were early recurrent stroke/transient ischemic attack (TIA) within 30 days, early neurological deterioration (END) within 7 days, and functional independence (modified Rankin Scale [mRS] ≤ 2 at 90 days). Pooled risk ratios (RRs) and mean differences (MDs) were calculated using fixed-effect models when statistical heterogeneity was low (I² ≤50%) and random-effects models when heterogeneity was substantial (I² >50%). This review was prospectively registered in PROSPERO (CRD420251144202).

Results

Five studies (n = 1,842) met eligibility criteria. Early PCSK9 inhibitor use was associated with a lower risk of recurrent stroke/TIA (5 studies, n = 1,842; RR 0.38, 95% CI 0.26–0.54; I²=45.5%; low certainty), all cause mortality (3 studies, n = 1,061; RR 0.48, 95% CI 0.30–0.77; I²=0%; low certainty), and early neurological deterioration (2 studies, n = 533; RR 0.56, 95% CI 0.36–0.88; I²=0%; low certainty), and was associated with a higher likelihood of functional independence (mRS ≤ 2 at 90 days) (2 studies, n = 533; RR 1.31, 95% CI 1.15– 1.50; I²=0%; very low certainty). LDLC was significantly reduced (5 studies, n = 1,842; MD − 0.91 mmol/L, 95% CI − 1.26 to − 0.57; I²=93%; very low certainty). The certainty of evidence was downgraded primarily due to the risk of bias in included studies and imprecision.

Conclusions

Early initiation of PCSK9 inhibitors after AIS was associated with a higher likelihood of favorable short-term clinical outcomes and substantial LDL-C reduction. These findings suggest that PCSK9 inhibitors may confer neurovascular benefits, warranting confirmation in larger trials.