Influenza vaccine wards off cardiovascular events, death in CAD patients

A meta-analysis of randomized trials has revealed that influenza vaccination is effective at preventing all-cause mortality, cardiovascular mortality, major acute cardiovascular events, and acute coronary syndrome (ACS) among patients with coronary artery disease (CAD), particularly in those with ACS.

“Influenza vaccination is a cheap and effective intervention and should be enforced as a standard secondary prevention therapy for CAD patients,” the researchers said.

The databases of Central, Embase, Medline, clinicaltrials.gov, and the World Health Organization International Clinical Trials Registry Platform were searched from inception to September 2021 for relevant studies. The researchers then summarized estimates using the Mantel-Haenzel method and a random-effects model. They also assessed heterogeneity using the I² statistic.

Five trials, involving a total of 4,187 patients, met the eligibility criteria. Of the studies, two included patients with ACS and three with stable CAD and ACS. [Am J Med 2023;136:466-475]

Influenza vaccination resulted in a significant decrease in the risks for all-cause mortality (relative risk [RR], 0.56, 95 percent confidence interval [CI], 0.38‒0.84), cardiovascular mortality (RR, 0.54, 95 percent CI, 0.37‒0.80), major acute cardiovascular events (RR, 0.66, 95 percent CI, 0.49‒0.88), and ACS (RR, 0.63, 95 percent CI, 0.44‒0.89).

Subgroup analysis revealed that the efficacy of influenza vaccine was consistent in these outcomes in ACS but failed to reach statistical significance in CAD. Vaccination also fell short of reducing the risk of revascularization (RR, 0.89, 95 percent CI, 0.54‒1.45), stroke or transient ischaemic attack (RR, 0.85, 95 percent CI, 0.31‒2.32), or heart failure hospitalization (RR, 0.91, 95 percent CI, 0.21‒4.00).

“This study may serve as a foundation for clinicians and future healthcare strategies to help increase influenza vaccination rates among the population with ischemic heart disease,” the researchers said.

Similar findings were found in a previous meta-analysis, which showed that influenza vaccination was most effective among patients with a recent history of ACS. [JAMA 2013;310:1711-1720]

“Previous studies and the results of this meta-analysis are consistent with the conclusion that influenza vaccine benefits CAD patients, reducing multiple hard outcomes (eg, all-cause mortality, cardiovascular mortality, and major acute cardiovascular events),” the researchers said.

Current guidelines by the American Heart Association, American College of Cardiology, and the European Society of Cardiology grade influenza vaccine as a class IB recommendation for CAD patients. However, based on available data from several studies, influenza vaccination could be graded as class IA in future guidelines. [J Am Coll Cardiol 2006;48:1498-1502; Eur Heart J 2021;42:1289-1367]

Mechanism

Infection with influenza virus could undermine atherosclerotic plaques. Acute viral infections, such as influenza and COVID-19, result in an inflammatory response known as the inflammation cascade, which then leads to an increased release of pro-inflammatory cytokines, such as interleukins 1, 6, and 8 and tumour necrosis factor α, according to the researchers.

“These cytokines activate inflammatory cells within atherosclerotic plaques and promote the deposition of immune complexes,” they said.

Moreover, prior studies have shown that macrophages in the coronary arteries may increase, causing plaque rupture and subsequent thrombosis. [Am J Cardiol 1997;80:11I-16I; Clin Cardiol 1993;16:761-762; Rev Cardiovasc Med 2014;15:168-175; Eur Heart J Suppl 2022;24:I84-I88]

Several studies also found that influenza viruses prefer vascular structures and that infections may lead to the progression of atherosclerosis. [Circulation 2003;107:762-768; Eur Heart J Suppl 2022;24:I84-I88]

“Because influenza vaccination reduces the risk of influenza infection, this may explain why it reduces the risk of undesirable outcomes as seen in our study,” the researchers said. “Although there is significant evidence supporting a link between influenza infections and ACS and cardiovascular events, further studies are still needed to understand the underlying mechanisms of this association.”