Statins for Acute Ischemic Stroke
Statins have been claimed to be effective in the acute phase of ischemic stroke. The potential positive actions of statins during an acute cerebrovascular ischemic event are 2-fold: a neuroprotective effect, limiting damage and improving recovery and a preventative effect on early recurrence. The aim of this systematic review was to assess the efficacy and safety of statins in the treatment of acute cerebrovascular ischemic events, both transient ischemic attack and ischemic stroke.
We searched the Cochrane Stroke Group's Trials Register (November 2010); the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 4); MEDLINE (1950–November 2010); and EMBASE (1980–November 2010). In an effort to identify further published, unpublished, and ongoing trials, we searched ongoing trials and research registers (November 2010), checked reference lists from relevant articles, and contacted authors.
We included all randomized controlled trials comparing statins (any type and dosage) versus placebo or no treatment administered within 2 weeks of the onset of acute ischemic stroke or transient ischemic attack.
Data Collection and Analysis
Two review authors independently selected studies for inclusion and extracted data. We assessed methodological quality and, when necessary, contacted study authors for additional data. We based quantitative analysis of outcome on the intention-to-treat principle. The primary outcomes were mortality from ischemic stroke and mortality from adverse drug effects, bleeding, and infections. We estimated the overall treatment effect by the pooled OR with 95% CI using a fixed-effect model (Mantel-Haenszel).
We included 8 randomized controlled trials involving 625 participants. Only 1 study was judged as “low risk” of bias. There were insufficient published data from the 8 studies for all planned primary and secondary outcomes. No patients died from ischemic stroke or from adverse drug effects, bleeding, or infections among the 444 participants in the 6 studies in which these outcomes were reported. Statin treatment did not reduce all-cause mortality compared with placebo or no treatment (OR, 1.51; 95% CI, 0.60–3.81) in the 431 patients enrolled in 7 studies (Figure). No cases of rhabdomyolysis (the breakdown of muscle fibers resulting in the release of muscle fiber contents (myoglobin) into the bloodstream) occurred in 274 patients enrolled in 3 studies.
Implications for Practice
Insufficient data were available from randomized trials to establish whether statins are safe and effective in cases of acute ischemic stroke and transient ischemic attack.
Implications for Research
From a public health perspective, because stroke is the leading cause of disability and a major cause of mortality, even a small benefit from the use of statins may be desirable. Given the limitations highlighted in our systematic review, no clear-cut conclusions can be drawn at this point. There is a need for an international, multicenter, randomized, placebo-controlled, double-blind study including hundreds of patients with acute ischemic stroke and a basal National Institutes of Health Stroke Scale score >3 to assess the efficacy and safety of a statin administered at a medium/high dose within 48 hours from the onset of symptoms. If this provides positive results, then, and only then, should researchers (re)investigate the safety and efficacy of statins in patients with transient ischemic attack or minor stroke.
Sources of Funding
Italian Medicines Agency (AIFA), Italy. Independent drug research program 2008, contract no. FARM8EHHBW, National Institute for Health Research, UK, Cochrane Review Incentive Scheme 2010.
This article is based on a Cochrane Review published in The Cochrane Library 2011, Issue 8 (see www.thecochranelibrary.com for information). Cochrane Reviews are regularly updated as new evidence emerges and in response to feedback, and The Cochrane Library should be consulted for the most recent version of the review.1
- Received September 14, 2011.
- Accepted October 14, 2011.
- © 2012 American Heart Association, Inc.
- Squizzato A,
- Romualdi E,
- Dentali F,
- Ageno W