Multivitamin Use Does Not Reduce Cardiovascular Risk in Men

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 Participant:

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.

JAMA. 2012;308(17):1751-1760. doi:10.1001/jama.2012.14805.

Zoledronic Acid Reduces Vertebral Fractures in Men with Osteoporosis

Background:

Fractures in men are a major health issue, and data on the antifracture efficacy of therapies for osteoporosis in men are limited. We studied the effect of zoledronic acid on fracture risk among men with osteoporosis.

Methods:

In this multicenter, double-blind, placebo-controlled trial, we randomly assigned 1199 men with primary or hypogonadism-associated osteoporosis who were 50 to 85 years of age to receive an intravenous infusion of zoledronic acid (5 mg) or placebo at baseline and at 12 months. Participants received daily calcium and vitamin D supplementation. The primary end point was the proportion of participants with one or more new morphometric vertebral fractures over a period of 24 months.

Results:

The rate of any new morphometric vertebral fracture was 1.6% in the zoledronic acid group and 4.9% in the placebo group over the 24-month period, representing a 67% risk reduction with zoledronic acid (relative risk, 0.33; 95% confidence interval, 0.16 to 0.70; P=0.002). As compared with men who received placebo, men who received zoledronic acid had fewer moderate-to-severe vertebral fractures (P=0.03) and less height loss (P=0.002). Fewer participants who received zoledronic acid had clinical vertebral or nonvertebral fractures, although this difference did not reach significance because of the small number of fractures. Bone mineral density was higher and bone-turnover markers were lower in the men who received zoledronic acid (P<0.05 for both comparisons). Results were similar in men with low serum levels of total testosterone. The zoledronic acid and placebo groups did not differ significantly with respect to the incidence of death (2.6% and 2.9%, respectively) or serious adverse events (25.3% and 25.2%).

Conclusions:

Zoledronic acid treatment was associated with a significantly reduced risk of vertebral fracture among men with osteoporosis.

(N Engl J Med 2012; 367:1714-1723November 1, 2012DOI: 10.1056/NEJMoa1204061

Funded by Novartis Pharma; ClinicalTrials.gov number, NCT00439647.)

Single Dose of Topical Ivermectin Kills Head Lice

Background:

The emergence of resistance to treatment complicates the public health problem of head-louse infestations and drives the need for continuing development of new treatments. There are limited data on the activity of ivermectin as a topical lousicide.

Methods:

In two multisite, randomized, double-blind studies, we compared a single application of 0.5% ivermectin lotion with vehicle control for the elimination of infestations without nit combing in patients 6 months of age or older. A tube of topical ivermectin or vehicle control was dispensed on day 1, to be applied to dry hair, left for 10 minutes, then rinsed with water. The primary end point was the percentage of index patients (youngest household member with ≥3 live lice) in the intention-to-treat population who were louse-free 1 day after treatment (day 2) and remained so through days 8 and 15.

Results:

A total of 765 patients completed the studies. In the intention-to-treat population, significantly more patients receiving ivermectin than patients receiving vehicle control were louse-free on day 2 (94.9% vs. 31.3%), day 8 (85.2% vs. 20.8%), and day 15 (73.8% vs. 17.6%) (P<0.001 for each comparison). The frequency and severity of adverse events were similar in the two groups.

Conclusions:

A single, 10-minute, at-home application of ivermectin was more effective than vehicle control in eliminating head-louse infestations at 1, 7, and 14 days after treatment.

(Funded by Topaz Pharmaceuticals [now Sanofi Pasteur]

N Engl J Med 2012; 367:1687-1693 November 1, 2012DOI: 10.1056/NEJMoa1200107