Multivitamins in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomized controlled trial.

JAMA

Nov 2012

DOI: 10.1001/jama.2012.14805

Citations:185

Influential Citations:9

Interventional (Human) Studies

Enhanced Details

Methods

Randomized, double-blind, placebo-controlled trial (2×2×2×2 factorial) in 14,641 male U.S. physicians aged ≥50 years; mean age 64.3 years; included men with and without prior cardiovascular disease at randomization; follow-up through June 1, 2011.

Intervention

Centrum Silver daily multivitamin; duration: median follow-up 11.2 years (end of follow-up June 1, 2011); taken daily.

Results

Daily multivitamin did not reduce major cardiovascular events versus placebo over about 11 years (HR 1.01; 95% CI 0.91-1.10; P=0.91). No significant effects on total MI (HR 0.93; 95% CI 0.80-1.09; P=0.39), total stroke (HR 1.06; 95% CI 0.91-1.23; P=0.48), cardiovascular death (HR 0.95; 95% CI 0.83-1.09; P=0.47), or total mortality (HR 0.94; 95% CI 0.88-1.02; P=0.13). Effect did not differ by baseline CVD history (P interaction = 0.62). Conclusion: A daily multivitamin did not reduce major cardiovascular events or other CV outcomes; findings do not support multivitamin use for CVD prevention in this population.

Limitations

Population limited to middle-aged and older male physicians (predominantly Caucasian); may limit generalizability to women or non-physician populations. Participants were generally well-nourished at baseline; results may not apply to individuals with nutrient deficiencies. Only one multivitamin formulation (Centrum Silver) studied; applicability to other formulations uncertain. Adherence and drop-ins occurred; although analyses adjusted, residual confounding possible. Multiple secondary analyses raise risk of type I error; results may not apply to earlier life or more diverse populations.

Abstract

CONTEXT Although multivitamins are used to prevent vitamin and mineral deficiency, there is a perception that multivitamins may prevent cardiovascular disease (CVD). Observational studies have shown inconsistent associations between regular multivitamin use and CVD, with no long-term clinical trials of multivitamin use. OBJECTIVE To determine whether long-term multivitamin supplementation decreases the risk of major cardiovascular events among men. DESIGN, SETTING, AND PARTICIPANTS The Physicians' Health Study II, a randomized, double-blind, placebo-controlled trial of a common daily multivitamin, began in 1997 with continued treatment and follow-up through June 1, 2011. A total of 14,641 male US physicians initially aged 50 years or older (mean, 64.3 [SD, 9.2] years), including 754 men with a history of CVD at randomization, were enrolled. INTERVENTION Daily multivitamin or placebo. MAIN OUTCOME MEASURES Composite end point of major cardiovascular events, including nonfatal myocardial infarction (MI), nonfatal stroke, and CVD mortality. Secondary outcomes included MI and stroke individually. RESULTS During a median follow-up of 11.2 (interquartile range, 10.7-13.3) years, there were 1732 confirmed major cardiovascular events. Compared with placebo, there was no significant effect of a daily multivitamin on major cardiovascular events (11.0 and 10.8 events per 1000 person-years for multivitamin vs placebo, respectively; hazard ratio [HR], 1.01; 95% CI, 0.91-1.10; P = .91). Further, a daily multivitamin had no effect on total MI (3.9 and 4.2 events per 1000 person-years; HR, 0.93; 95% CI, 0.80-1.09; P = .39), total stroke (4.1 and 3.9 events per 1000 person-years; HR, 1.06; 95% CI, 0.91-1.23; P = .48), or CVD mortality (5.0 and 5.1 events per 1000 person-years; HR, 0.95; 95% CI, 0.83-1.09; P = .47). A daily multivitamin was also not significantly associated with total mortality (HR, 0.94; 95% CI, 0.88-1.02; P = .13). The effect of a daily multivitamin on major cardiovascular events did not differ between men with or without a baseline history of CVD (P = .62 for interaction). CONCLUSION Among this population of US male physicians, taking a daily multivitamin did not reduce major cardiovascular events, MI, stroke, and CVD mortality after more than a decade of treatment and follow-up. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00270647. show less