Flu vaccine linked to lower risk for CV events

Use of the influenza vaccine was associated with lower risk for major adverse CV events in a meta-analysis of randomized controlled trials.

Jacob A. Udell, MD, MPH, FRCPC, and colleagues analyzed six randomized clinical trials (five published, one unpublished) of influenza vaccine use in people with high risk for CVD. In all studies, CV events were included as efficacy or safety outcomes.

The trials analyzed covered 6,735 patients (mean age, 67 years; 51.3% women; 36.2% with cardiac history; mean follow-up time, 7.9 years). The primary endpoint was a composite of major adverse CV events, including CV death or hospitalization for MI, unstable angina, stroke, HF and urgent coronary revascularization within 12 months of follow-up. The secondary endpoint was CV mortality and other individual CV events within 12 months of follow-up.

Vaccine group had fewer CV events

Among participants in the published trials, influenza vaccine was associated with lower risk for the primary composite endpoint (vaccine group, 2.9%; placebo or control group, 4.7%; RR=0.64; 95% CI, 0.48-0.86). The absolute risk difference was 1.74% (95% CI, 0.81-2.67) and the number needed to treat to prevent one major adverse CV event was 58 (95% CI, 38-124).

Adding participants from the unpublished trial did not change the results (vaccine group, 2.9%; placebo or control group, 4.6%; RR=0.64; 95% CI, 0.49-0.84), Udell and colleagues found.

The researchers also conducted a subgroup analysis of three trials of patients with CAD (n=1,389). Among those participants, influenza vaccine was strongly associated with lower risk for major adverse CV events in patients with a history of ACS within 12 months of randomization (vaccine group, 10.25%; placebo or control group, 23.1%; RR=0.45; 95% CI, 0.32-0.63) compared with patients with stable CAD (vaccine group, 6.9%; placebo or control group, 7.4%; RR=0.94; 95% CI, 0.55-1.61; P for interaction=.02). The absolute risk difference for patients with recent ACS was 12.9% (95% CI, 7.75-18) and the number needed to treat to prevent one major adverse CV event was eight (95% CI, 6-13). Adding participants from the unpublished trial did not change the results.

CV mortality at 12 months did not differ between vaccinated and unvaccinated participants (vaccine group, 1.3%; placebo or control group, 1.7%; RR=0.81; 95% CI, 0.36-1.83). There was also no difference in all-cause mortality at 12 months (vaccine group, 1.9%; placebo or control group, 2.1%; RR=0.85; 95% CI, 0.45-0.61).

“The greatest treatment effect was seen among the highest-risk patients with more active coronary disease,” Udell, a cardiologist at Women’s College Hospital, Toronto, and colleagues wrote. “A large, adequately powered, multicenter trial is warranted to address these findings and assess individual [CV] endpoints.”

Results biologically plausible

Kathleen M. Neuzil

In a related editorial, Kathleen M. Neuzil, MD, MPH, of PATH, Seattle, wrote that, “It is biologically plausible that influenza vaccine could prevent serious [CV] outcomes, and this is supported by animal models and epidemiological studies examining the relationship of [CV] disease and influenza virus circulation.”

According to Neuzil, the overall absolute risk difference of 1.74% is plausible, but the absolute risk difference of 12.9% for patients with recent ACS appears to be too high and “suggests possible design flaws and residual bias in at least some of the individual studies that contributed to the meta-analysis.”

For more information:

Neuzil KM. JAMA. 2013;310:1681-1682.

Udell JA. JAMA. 2013;310:1711-1720.

Disclosure: See the full study for a list of the researchers’ relevant financial disclosures. Neuzil reports no relevant financial disclosures.