Our guest contributor is Dr. Joshua Goldenberg, a naturopathic physician, professor, researcher, and creator of Dr. Journal Club. He has presented nationally and internationally on evidence-based medicine as well as probiotics and research methodology. He created www.DrJournalClub.com which is an online repository of educational videos serving to keep medical professionals up-to-date on current and relevant research as well as hone their evidence-based medicine skills. In Part 4 of the Flu Shot Research series, he continues his review of the current state of evidence for flu vaccinations for high-risk cardiac patients.
Today we will review a 2013 systematic review and meta-analysis published in JAMA that evaluates whether the flu vaccine prevents major coronary events in high-risk cardiac patients. The authors found six trials, five of which were published and used in the primary analysis, which included over 6,700 participants. The primary outcome was a composite of major cardiovascular events. They also looked at mortality as well, although you need a huge amount of participants to be adequately powered to see an effect there.
The authors used the Cochrane Risk of Bias tool to evaluate the studies for risk of bias. They did a grey literature search to identify all studies and they also used a funnel plot to visually inspect for publication bias. Their major subgroup analysis of interest was those patients who had had an acute coronary syndrome (ACS) in the past 12 months versus those with stable coronary artery disease (CAD).
What they found is that overall there was a reduction in risk of major coronary events by about a third – so a rather impressive effect size! The reduction in risk for mortality was 19% but it was not statistically significant. When they looked at those who had a recent cardiac event – so those at very high baseline risk – what they found was that the effect was even greater: a 55% relative risk reduction. This finding was based only on three studies that looked at patients in this risk category.
It is important to discuss absolute risk reduction when you can, as relative risk reductions can be deceiving. This high-risk group of patients who had an ACS in the past year were 23% likely to have another event in a year. If you vaccinated these participants however the risk reduced to 10%. So this is an absolute risk difference of 13% (versus the relative risk reduction of 55%). To calculate the numbers needed to treat, or vaccinate in this case, you simply use the inverse of this absolute risk reduction, which is eight. So you need to vaccinate eight very high-risk cardiac patients to prevent one cardiac event.
There are some issues with this paper. Specifically, they really only had five studies for their primary meta-analysis and once they stratified by timing of ACS they only had three on the high-risk subgroup, only one of which was high quality (low risk of bias). However, the effect they saw was large, clinically significant, consistent across the studies they had, and biologically plausible. I think the take home is that vaccinating against the flu in cardiac patients and especially high-risk cardiac patients is essential.