Published Online
on April 12, 2007

A more recent version of this article appeared on June 1, 2007

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Submitted on October 13, 2006
Revised on January 7, 2007
Accepted on January 11, 2007

Combining Multiple Approaches for the Secondary Prevention of Vascular Events After Stroke. A Quantitative Modeling Study

Daniel G. Hackam BSc, MD, PhD, FRCPC^* and J. David Spence MD, FRCPC, FAHA

From the Division of Clinical Pharmacology & Toxicology (D.G.H.), Department of Medicine, University of Toronto, Canada; the Cardiac Rehabilitation & Secondary Prevention Program (D.G.H.), Toronto Rehabilitation Institute, and Institute for Clinical Evaluative Sciences, Canada; the Stroke Prevention and Atherosclerosis Research Center (J.D.S.), Robarts Research Institute, London, Canada; and the Division of Clinical Pharmacology and Department of Clinical Neurological Sciences (J.D.S.), University of Western Ontario, London, Canada.

^* To whom correspondence should be addressed. E-mail: Daniel.Hackam{at}ICES.ON.CA.

Background and Purpose--Numerous effective strategies for the secondary prevention of cardiovascular events in high-risk patients have now been established. We sought to calculate the cumulative benefit of combining multiple strategies for preventing recurrent events in patients with a history of ischemic stroke or transient ischemic attack.

Methods--A comprehensive literature search was undertaken to identify meta-analyses of randomized controlled trials reporting on the efficacy of secondary prevention strategies. The baseline incidence of vascular events was modeled from the Life Long After Cerebral Ischemia study. Strategies were combined on a multiplicative scale and cumulative risk reductions were computed over a 5-year interval.

Results--The combination of 5 proven strategies applied to survivors of an initial stroke or transient ischemic attack--dietary modification, exercise, aspirin, a statin, and an antihypertensive agent--could result in a cumulative relative risk reduction of 80%. Given a 5-year major cardiovascular event rate of 24%, this translates to a number needed to treat of about 5. Further gains would result from applying multimodality therapy over longer intervals and enriching the base strategy with dual antiplatelet therapy, high-dose statins, and more intensive blood pressure-lowering. Even more benefit would be present in high-risk subgroups with the addition, where appropriate, of carotid endarterectomy, moderate intensity oral anticoagulants, glycemic control, and smoking cessation.

Conclusions--At least four-fifths of recurrent vascular events in patients with cerebrovascular disease might be prevented by application of a comprehensive, multifactorial approach.

Key words: cerebrovascular disease • medical Rx • prevention • risk factor modification • secondary prevention • statistical models • stroke • systematic review

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Peter M. Rothwell
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