Statins in Acute Ischemic Stroke: A Systematic Review

Abstract

Background and purpose: Statins have pleiotropic effects of potential neuroprotection. However, because of lack of large randomized clinical trials, current guidelines do not provide specific recommendations on statin initiation in acute ischemic stroke (AIS). The current study aims to systematically review the statin effect in AIS.

Methods: From literature review, we identified articles exploring prestroke and immediate post-stroke statin effect on imaging surrogate markers, initial stroke severity, functional outcome, and short-term mortality in human AIS. We summarized descriptive overview. In addition, for subjects with available data from publications, we conducted meta-analysis to provide pooled estimates.

Results: In total, we identified 70 relevant articles including 6 meta-analyses. Surrogate imaging marker studies suggested that statin might enhance collaterals and reperfusion. Our updated meta-analysis indicated that prestroke statin use was associated with milder initial stroke severity (odds ratio [OR] [95% confidence interval], 1.24 [1.05-1.48]; P=0.013), good functional outcome (1.50 [1.29-1.75]; P<0.001), and lower mortality (0.42 [0.21-0.82]; P=0.0108). In-hospital statin use was associated with good functional outcome (1.31 [1.12-1.53]; P=0.001), and lower mortality (0.41 [0.29-0.58]; P<0.001). In contrast, statin withdrawal was associated with poor functional outcome (1.83 [1.01-3.30]; P=0.045). In patients treated with thrombolysis, statin was associated with good functional outcome (1.44 [1.10-1.89]; P=0.001), despite an increased risk of symptomatic hemorrhagic transformation (1.63 [1.04-2.56]; P=0.035).

Conclusions: The current study findings support the use of statin in AIS. However, the findings were mostly driven by observational studies at risk of bias, and thereby large randomized clinical trials would provide confirmatory evidence.

Keywords: Acute ischemic stroke; Mortality; Outcome; Statins; Stroke severity; Symptomatic hemorrhagic transformation.

Figure 1.

Summary of study selection. ^*11 articles were overlapped. CEA, carotid endarterectomy; RCT, randomized controlled trial.

Figure 2.

Association of prestroke statin use and initial stroke severity (A), good functional outcome (B), and short-term mortality (C, pooling studies providing OR; D, pooling studies providing HR). Values of OR or HR greater than 1.0 indicate that prestroke statin use was associated with milder initial stroke severity (A), good functional outcome (B), and higher risk of mortality (C and D). SE, standard error; IV, inverse variance; CI, confidence interval.

Figure 3.

Association of in-hospital statin use and good functional outcome (A), and short-term mortality (B, pooling studies providing ORs; C, pooling studies providing HRs). Values of OR or HR greater than 1.0 indicate that in-hospital statin use was associated with good functional outcome (A), and higher risk of mortality (B and C). SE, standard error; IV, inverse variance; CI, confidence interval.

Figure 4.

Association of statin withdrawal during hospitalization and poor functional outcome. Values of ORs greater than 1.0 indicate that statin withdrawal during hospitalization was associated with poor functional outcome. SE, standard error; IV, inverse variance; CI, confidence interval.

Figure 5.

Association of statin use and good functional outcome (A), 90-day mortality (B), and symptomatic hemorrhagic transformation (C). Values of ORs than 1.0 indicate that statin use was associated with good functional outcome (A), higher risk of mortality (B), and higher risk of symptomatic hemorrhagic transformation (C). SE, standard error; IV, inverse variance; CI, confidence interval.

Figure 6.

Association of statin use and post-stroke infection risk. Values of ORs greater than 1.0 indicate that statin use was associated with an increased risk of post-stroke infection. SE, standard error; IV, inverse variance; CI, confidence interval.