The drive to immunize people against flu received a shot in the arm with a meta-analysis published in the Oct. 23/30 issue of JAMA that found vaccine use was associated with a lower risk of cardiovascular complications.

“If severe influenza-associated morbidity and mortality is in part due to acutely triggered ischemic cardiovascular events, and a vaccine preventing influenza could decrease the risk of cardiovascular events, then this therapy could address a sizable component of residual cardiovascular risk not addressed by current therapy and provide yearlong coverage through one simple inoculation,” wrote Jacob A. Udell, MD, MPH, of Women’s College Hospital in Toronto, and colleagues.

Udell et al conducted a meta-analysis of randomized clinical trials on influenza vaccines that included cardiovascular events as outcomes. They identified trials from 1946 to August 2013 through MEDLINE, EMBASE and the Cochrane Library Central Register of Controlled Trials. The primary endpoint was a composite of major adverse cardiovascular events (MACE). The secondary endpoint was cardiovascular mortality and individual cardiovascular events.

They reviewed trial designs with either a placebo, control or intense vs. standard vaccination; duration of follow-up between 28 days and one year; and a sample size of 50 or more. One unpublished and five published randomized clinical trials that enrolled 6,735 patients fit their inclusion criteria.

In the published trials, 2.9 percent of patients who received a flu vaccine developed MACE compared with 4.7 percent in the placebo or control groups. That translated into 58 patients treated per one MACE avoided.

A subgroup analysis of three clinical trials that assessed patients with coronary artery disease found that those with a history of a recent acute coronary syndrome had a MACE rate of 10.25 percent compared with 23.1 percent in the placebo or control groups.     

Udell et al proposed that mechanisms such as avoiding atherosclerotic plaque rupture may explain a flu shot’s possible powers for reducing MACE risk. “Future research with an adequately powered multicenter trial to confirm the efficacy of this low-cost, annual, safe, easily administered, and well-tolerated therapy to reduce cardiovascular risk beyond current therapies is warranted,” they wrote.

In an accompanying editorial, Kathleen M. Neuzil, MD, MPH, of the Vaccine Access and Delivery program at PATH in Seattle, pointed out that only one of the three high-quality randomized trials used in the meta-analysis found that flu vaccines showed a benefit against cardiovascular events, and that trial enrolled only 658 participants.

“[A]s with all meta-analyses, the findings are limited by the quality of the underlying studies and do not imply causation,” she wrote. “Regardless of whether influenza vaccine reduces cardiovascular disease, the known morbidity of influenza in older adults with and without high-risk conditions and the known efficacy of the vaccine warrant its use.”

The flu vaccination rate for the general population in the U.S. is about 30 percent, Udell and colleagues wrote. Only about half of patients under 65 years old with high-risk conditions get an annual flu shot, Neuzil added, and only two-thirds of elderly patients are vaccinated.  She encouraged physicians to recommend to annual influenza vaccinations to their patients, which she argued was an effective way to improve vaccination rates and outcomes.