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Am Fam Physician. 2004;69(11):2716-2719

Statin Use After Stroke and TIA

The Stroke Council of the American Heart Association and American Stroke Association has released a scientific advisory on the use of statins. “Statins After Ischemic Stroke and Transient Ischemic Attack” appears in the April 2004 issue ofStroke and is available online at

Based on results of numerous large-scale randomized trials, the vast majority of patients with a history of ischemic stroke or transient ischemic attack could benefit from statin use.

Although prevention of a second stroke was not the primary aim of any completed study, some studies included patients whose primary reason for entry was stroke. Multiple studies have shown that statins reduce risk of stroke in patients with coronary artery disease and elevated total or low-density lipoprotein (LDL) cholesterol levels. Recently, the Heart Protection Study showed that 40 mg per day of simvastatin reduced the risk of stroke by 25 percent among patients with coronary artery disease, other occlusive arterial disease, or diabetes. In the subgroup enrolled with prior ischemic stroke or transient ischemic attack but no coronary artery disease, the risk of major vascular events (i.e., coronary events, stroke, or revascularization) was reduced by 21 percent (absolute risk reduction, 1 percent per year; number needed to treat, 102 to prevent one event each year). Benefits persisted in those with LDL levels lower than 116 mg per dL (3.0 mmol per L) or total cholesterol levels lower than 193 mg per dL (5.0 mmol per L).

A meta-analysis also shows that the benefit of statins in reducing the rates of stroke and cardiovascular events is independent of cholesterol levels and occurs with other statins. Given early benefits in trials of acute coronary syndromes, statin initiation during hospitalization for first ischemic stroke of atherosclerotic origin is probably justified and may increase rates of long-term use. Results of the ongoing Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial will provide additional information about the role of statins in the minority of patients with prior stroke but no history of coronary heart disease, other occlusive arterial disease, or diabetes.

Antioxidants Are of Little, If Any, Benefit in CVD

The Agency for Healthcare Research and Quality (AHRQ) has released an evidence report on antioxidants and cardiovascular disease. “Effect of Supplemental Antioxidants Vitamin C, Vitamin E, and Coenzyme Q10 for the Prevention and Treatment of Cardiovascular Disease” is available online at

To assess the efficacy of three antioxidants, vitamins E and C, and coenzyme Q10, in the prevention and treatment of cardiovascular disease (CVD) or modification of known risk factors for CVD, the AHRQ performed a detailed review of the scientific literature. Among the findings are the following:

  • The available evidence did not generally support the assertion that there was any positive benefit associated with the use of vitamin E either alone or in the combinations tested for the prevention of all-cause death or cardiovascular death. Neither was there any evidence of significant harm from the same intervention. An effect of vitamin E on overall mortality and on cardiovascular mortality reported in one trial was only observed in a four-way analysis (that is, comparing each arm of the 2 × 2 factorial study separately), and not seen in the two-way analysis (comparing all subjects who received vitamin E with all those who did not). The investigators themselves noted that the results in the four-way analysis were probably due to chance and concluded that vitamin E supplementation conferred no benefit. Reduction in all-cause mortality (by 9 percent) was reported in another study and was caused primarily by a decrease in cancer deaths, not cardiovascular deaths. Therefore, there is little evidence that vitamin E supplementation results in a reduction in cardiovascular mortality.

  • For the risk of myocardial infarction (MI), fatal and nonfatal, the evidence regarding results of supplementation with vitamin E alone or in combination is mixed. No pooled analysis yielded a beneficial or adverse effect for vitamin E supplementation, either alone or in combination. However, individual studies did report significant effects. One study reported a benefit on fatal MI but a nonsignificant adverse effect on non-fatal MI. Furthermore, the beneficial effects in this study were seen only in the four-way analysis and not in the larger two-way analysis. The Alpha-Tocopherol Beta Carotene (ATBC) trials reported a significant adverse effect of vitamin E on fatal MI but a nearly significant beneficial effect of vitamin E on nonfatal MI. While there were distinct differences in the two trials (ATBC assessed 50 mg of vitamin E, the other trial assessed 300 mg, but the baseline risk of fatal and nonfatal MI was approximately equivalent in the two studies), such disparities in results cast doubt on the observed effects being brought about by a causal relationship, because consistency of effect and a dose response effect are two important constituents of causality.

  • Supplementation with vitamin E alone and in combinations in doses ranging from 100 IU to 1,200 IU did not demonstrate a statistically significant effect on serum lipids after at least eight weeks and no more than 24 weeks of treatment. Two large primary prevention trials reported clinically insignificant (but statistically significant) changes in these outcomes. Thus, there is no evidence that vitamin E, alone or in combinations, has a clinically and statistically significant favorable or unfavorable effect on lipids.

  • There have been few studies of the use of coenzyme Q10 that have enrolled at least 60 patients and completed at least six months' duration of treatment and measured clinical outcomes. A meta-analysis of the effect of coenzyme Q10 on indices of cardiac function concluded that its use was associated with a substantial improvement. This conclusion was not confirmed by two subsequent randomized trials. The studies reporting clinical outcomes yielded mixed results. Two studies reported distinctly favorable clinical outcomes for coenzyme Q10-treated patients. However, one study probably had a serious potential flaw in design and execution in that it is not reported to be placebo-controlled or blinded with respect to outcome measurement. The second study is reported in insufficient detail to allow an adequate assessment of the enrolled population or the results. Four subsequent studies reported either no or clinically small improvements. Therefore, the value of coenzyme Q10 supplementation in patients with CVD is still an open question, with convincing evidence neither supporting nor refuting evidence of benefit or harm.

  • Four studies assessing vitamin C (mostly in combination with vitamin E) provide scant evidence that these combinations of antioxidant supplements have any cardiovascular health benefits. The only reported benefit was in the Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) Study, and that was in an intermediate outcome only, and then only in the subpopulation of male smokers. The Heart Protection Study, in particular, because of its size and follow-up, provides good evidence that these antioxidant supplements in these doses are unlikely to have any substantial effects on CVD outcomes.

Educational Booklets for Older Adults

The Council on Family Health, the U.S. Food and Drug Administration, and the Administration on Aging (AoA) have released a new booklet on appropriate medicine use in older adults. The booklet, “Medicines and You: A Guide for Older Adults” is available in English and Spanish versions by calling the AoA's Eldercare Locator at 800–677–1116 or online at

The 17-page booklet provides information for older adults about the use of prescription and over-the-counter medicines, facts about drug interactions, tips for talking to physicians and pharmacists, and ways older adults can help lower their medicine costs. The booklet also features “My Medicine Record,” a chart on which older adults can list the medicines they take and other important health information.

The Agency for Healthcare Research and Quality (AHRQ) has released a booklet for older adults on staying healthy. “The Pocket Guide to Staying Healthy at 50+” is available by calling the AHRQ Publications Clearinghouse at 800–358–9295 and is available online in English at and in Spanish at

The pocket guide includes tips and recommendations on good health habits, screening tests, and immunizations. It provides charts to help track personal health information and includes questions to ask health care professionals, as well as resources to contact for additional information.

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