American Heart Association (AHA) 2012 Scientific Sessions: Page 2 of 2

February 19, 2013

The authors randomized patients in a 1:1 ratio to receive 30 µg/kg serelaxin or placebo daily, administered intravenously for 48 hours. Patients were enrolled between October 2009 and February 2012 at 96 sites across 11 countries. They received the medication within 16 hours of hospitalization. Most patients had elevated systolic blood pressure (mean, 142 mm Hg).

Over an 180-day follow-up, there was a significant improvement favoring the serelaxin group in cardiovascular mortality (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.41-0.96; P=.028) as well as in all-cause death (HR, 0.63; 95% CI, 0.43-0.93; P=.02). There were also significant improvements in the signs and symptoms of congestion at day 2.

From baseline through day 5, there was a 19.4% increase in the area under the curve for dyspnea relief in patients who took serelaxin compared with placebo (P=.0075). Teerlink said that results showed serelaxin improved survival according to the authors’ prespecified criteria. No significant difference in cardiovascular death or heart failure rehospitalization through day 60 was observed (HR, 1.02; 95% CI, 0.74-1.41; P=.89). There was a 30% reduction in cardiovascular deaths in the serelaxin group but a 20% increase in rehospitalizations in patients who took serelaxin, although the differences were not statistically significant.—Tim Casey

The study was funded by Corthera, a Novartis affiliate company.

Use of Daily Multivitamin Does Not Reduce Risk of Cardiovascular Disease

Older male physicians who took a multivitamin every day for more than a decade had similar rates of major cardiovascular events, total myocardial infarction, and total stroke compared with a group that took a placebo, according to a randomized, double-blind, placebo-controlled, factorial design study.

Lead author Howard D. Sesso, MD, associate professor, Brigham and Women’s Hospital, Boston, MA, presented the findings in a late-breaking abstract session at the AHA meeting. Results were simultaneously published online in the Journal of the American Medical Association (2012;308[17]:1751-1760). The trial was part of the Physicians’ Health Study II that includes 14,641 male physicians in the United States who are 50 years of age or older. Of the participants, 7641 had enrolled in the Physicians’ Health Study I from 1982 through 1996, during which they received aspirin and beta-carotene via mail to test if the products prevented cardiovascular disease and cancer. The remaining 7000 physicians were from part 2 of the study, which began in 1997 and is ongoing.

Sesso said more than half of adults in the United States take vitamin supplements, and more than one-third take multivitamins. He indicated that components of multivitamins might reduce the risk of cardiovascular disease, although observational studies have not demonstrated that association. This is the first large, long-term, randomized trial testing multivitamins in preventing cardiovascular disease and other chronic diseases, according to Sesso. He said the individual trials tested higher doses of vitamins and minerals, whereas multivitamins contain lower doses of the individual vitamins and minerals in combination.

Participants in the study took a multivitamin (n=7317) or placebo (n=7324) daily. Cardiovascular disease and cancer were the primary outcomes, while eye disease and cognitive function were secondary outcomes. The primary cardiovascular outcome was major cardiovascular events, defined as the composite of nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death.

The researchers used a monthly calendar pack to help physicians adhere to their regimens. The mean follow-up was 11.2 years. At 4 years, 77% of participants adhered to the multivitamin regimen; at 8 years, the adherence rate was 72%; and at study end, the rate was 67%. The groups were well balanced. The mean age was 64 years, and mean body mass index was 26.0 kg/m2. The participants were healthy: approximately 3.5% were smokers, 62% exercised at least once per week, 77% took aspirin, and daily intake of fruits and vegetables was higher compared with the general population, according to Sesso.

There were 876 major cardiovascular events in the multivitamin group and 856 in the placebo group (hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.91-1.10; P=.91). Total myocardial infarctions were 317 and 335, respectively (HR, 0.93; 95% CI, 0.80-1.91; P=.39), while instances of total stroke were 332 and 311, respectively (HR, 1.06; 95% CI, 0.91-1.23; P=.48).

There was also no effect for primary or secondary prevention of cardiovascular disease among participants with or without a history of cardiovascular disease. Sesso noted that there were 27 deaths due to myocardial infarction in the multivitamin group compared with 43 in the placebo group, which he deemed as a “borderline reduction” (HR, 0.61; 95% CI, 0.38-0.995; P=.048). “We had a very small number of events,” Sesso said. “We consider that to be interesting but exploratory at this point.”—Tim Casey

The study was funded by the National Institutes of Health and the BASF Corporation. Study packaging was provided by DSM 
Nutritional Products Inc.