Quality of Evidence and Limitations
Overall, our findings are based on a relatively small number of cardiovascular events (246 major adverse cardiovascular events and 97 cardiovascular deaths) among trials that varied in study design, intended primary outcomes, and patient populations. Subsequently, individual outcome analyses were of limited power. Moreover, several studies have design concerns regarding bias from inadequate randomization, concealment, and end point adjudication, which may limit our interpretation of the association of influenza vaccination with a lower risk of cardiovascular events.35
For instance, a significant difference in the cardiovascular risk associated with influenza vaccine compared with placebo was detected among the subgroup of trials recording events as primary (efficacy) compared with secondary (safety) end points. This finding could suggest heterogeneity in outcome ascertainment between trials; however, it should be considered in context of multiple testing and chance of type I error.
In addition, events such as unstable angina, cardiac ischemia, and coronary revascularization events included in a composite primary end point with myocardial infarction or cardiovascular death may not represent equal weighting of cardiovascular morbidity.
Finally, our meta-analysis comprised a mix of both primary and secondary prevention populations, challenging our ability to distinguish the association of influenza vaccine with lower cardiovascular risk in each group.
The strengths of the current study include efforts to identify and systematically review all influenza vaccine RCTs since the inception of major biomedical literature databases, thereby limiting the likelihood of publication bias and risk of confounding from nonrandomized studies. In addition, we performed a number of sensitivity analyses that revealed no suggestion of inconsistency among trial results or missing data confirming the robustness of our primary results. In fact, funnel plots suggest potential small trials of cardiovascular benefit may remain unpublished.
Clinical and Policy Implications
The widespread influenza activity of 2012-2013 was a strong reminder of the potential cardiovascular complications that may occur in association with a severe respiratory tract infection.67 Greater attention to prevention of cardiovascular events is therefore imperative to address the specific pathophysiology underlying this complication, particularly in elderly patients.
Influenza vaccination may prevent cardiovascular events via avoidance of atherosclerotic plaque rupture or other forms of cardiac injury in a vulnerable patient and represents a simple once-annual protective therapy to reduce cardiovascular events. This finding has considerable clinical and health policy importance, given the profound underuse of vaccination among the general public and the potential impact this preventive strategy may have on high-risk patients.60,61
Within this global meta-analysis of RCTs that studied patients with high cardiovascular risk, influenza vaccination was associated with a lower risk of major adverse cardiovascular events within 1 year. Influenza vaccination was particularly associated with cardiovascular prevention in patients with recent ACS.
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.If I understand the authors, they're saying this is a glimpse of a promising new direction for research, not a thunderbolt promising an end to heart attacks and strokes.