title: Multivitamins in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomized controlled trial.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  Daily multivitamin or placebo.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00270647.
authors.affiliation: Division of Preventive Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02215, USA. hsesso@hsph.harvard.edu
authors.forename: Howard D
authors.initials: HD
authors.lastname: Sesso
authors.forename: William G
authors.initials: WG
authors.lastname: Christen
authors.forename: Vadim
authors.initials: V
authors.lastname: Bubes
authors.forename: Joanne P
authors.initials: JP
authors.lastname: Smith
authors.forename: Jean
authors.initials: J
authors.lastname: MacFadyen
authors.forename: Miriam
authors.initials: M
authors.lastname: Schvartz
authors.forename: JoAnn E
authors.initials: JE
authors.lastname: Manson
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Glynn
authors.forename: Julie E
authors.initials: JE
authors.lastname: Buring
authors.forename: J Michael
authors.initials: JM
authors.lastname: Gaziano
mesh_terms: D000368:Aged; D002318:Cardiovascular Diseases / Q000401:mortality / Q000517:prevention & control*; D004311:Double-Blind Method; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000401:mortality / Q000517:prevention & control*; D010820:Physicians; D020521:Stroke / Q000517:prevention & control*; D016896:Treatment Outcome; D014815:Vitamins / Q000627:therapeutic use*
chemical_list: D014815:Vitamins