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(Stroke. 2004;35:1908.)
© 2004 American Heart Association, Inc.

Original Contributions

Postintervention Effect of Alpha Tocopherol and Beta Carotene on Different Strokes

A 6-Year Follow-Up of the Alpha Tocopherol, Beta Carotene Cancer Prevention Study

Markareetta E. Törnwall, MD, PhD; Jarmo Virtamo, MD, PhD; Pasi A. Korhonen, PhD; Mikko J. Virtanen, MSc; Demetrius Albanes, MD Jussi K. Huttunen, MD, PhD

From the National Public Health Institute (M.E.T., J.V., P.A.K., M.J.V., J.K.H.), Helsinki, Finland; and the National Cancer Institute (D.A.), Bethesda, Md.

Correspondence to Dr Markareetta E. Törnwall, National Public Health Institute, Department of Epidemiology and Health Promotion, Mannerheimintie 166, 00300 Helsinki, Finland. E-mail markareetta.tornwall{at}ktl.fi

Background and Purpose— In the Alpha Tocopherol, Beta Carotene Cancer Prevention Study, alpha tocopherol supplementation decreased risk of cerebral infarction by 14% (95% CI, –25% to –1%), and beta carotene increased risk of intracerebral hemorrhage by 62% (95% CI, 10% to 132%). We report here the 6-year postintervention effects of alpha tocopherol and beta carotene supplementation on stroke and its subtypes.

Methods— A total of 29 133 male smokers, aged 50 to 69 years, were randomized to receive 50 mg of alpha tocopherol, 20 mg of beta carotene, both, or placebo daily for 5 to 8 years. At the beginning of the post-trial follow-up, 24 382 men were still at risk for first-ever stroke. During the post-trial follow-up, 1327 men experienced a stroke: 1087 cerebral infarctions, 148 intracerebral hemorrhages, 64 subarachnoid hemorrhages, and 28 unspecified strokes.

Results— Post-trial risk for cerebral infarction was elevated among those who had received alpha tocopherol compared with those who had not (relative risk [RR], 1.13; 95% CI, 1.00 to 1.27), whereas beta carotene had no effect (RR, 0.97; 95% CI, 0.86 to 1.09). Alpha tocopherol supplementation was associated with a postintervention RR of 1.01 (95% CI, 0.73 to 1.39) for intracerebral hemorrhage and 1.38 (95% CI, 0.84 to 2.26) for subarachnoid hemorrhage. The corresponding RRs associated with beta carotene supplementation were 1.38 (95% CI, 0.99 to 1.91) and 1.09 (95% CI, 0.67 to 1.77), respectively.

Conclusions— Neither alpha tocopherol nor beta carotene supplementation had any postintervention preventive effects on stroke. The post-trial increase in cerebral infarction risk among recipients of alpha tocopherol may present a rebound of the reduced risk of cerebral infarction during the intervention.

Key Words: stroke • primary prevention • randomized controlled trials • antioxidants