Meta-Analysis Finds Flu Vaccine Halves CVD Risk; Skeptics Not Convinced

Marlene Busko

November 03, 2012

TORONTO — Could a simple flu shot cut the risk of having a major adverse cardiovascular event (MACE) within a year by half? This is the provocative conclusion researchers found in a meta-analysis of four trials of more than 3000 patients [1].

Speaking with heartwire after presenting here at the Canadian Cardiovascular Congress 2012, Dr Jacob Udell (University of Toronto, ON) admitted, "The skeptics . . . are right. There are no pills out there that reduce your risk by 50%. It is a profound finding, and if that's actually the case, this stuff should be in the water!"

On the other hand, "even if the advantage were a 10% reduction, you still would have a major improvement in cardiovascular clinical prevention, as well as cost-effectiveness and burden on the healthcare system," he argued.

The team performed a systematic literature review and identified only four trials that met their inclusion criteria. The trials, in the Netherlands, Argentina, Poland, and Thailand, were conducted from 1994 to 2008, when institutional review boards in the US would have likely found it unethical to deprive patients of receiving the flu shot, Udell noted.

A total of 3227 patients were enrolled: 1580 with no established CVD, 796 with early post-acute coronary syndrome, and 851 with stable CVD. About half received the influenza vaccine, and the other half typically received a placebo vaccine.

After one year, there were 187 MACE events (defined as MI, stroke, or cardiac death), and the flu vaccine provided an approximate 50% reduction in MACE events (odds ratio [OR] 0.52; p=0.0002).

There were 65 cardiovascular deaths and 70 total deaths, with a trend to fewer deaths in the treated patients.

This meta-analysis cannot prove how the influenza vaccine may be cardioprotective, Udell admitted, but he noted that two provocative theories--related to vulnerable patients or vulnerable plaque--might explain the science behind this effect. The flu shot may protect patients with multiple cardiovascular risk factors from getting respiratory infections that might lead to MI or stroke. Or it might prevent inflammation that may trigger rupture of vulnerable plaque.

The small number of events and the limitations in the designs of the four trials make it difficult to draw firm conclusions, he also acknowledged. The group is seeking funding to conduct a large, multicenter, prospective trial.

"Hard-to-Believe," "Pleiotropic "Effect

This study is "interesting and sheds some light [on the] pleiotropic effects of vaccination besides preventing flu," said comoderator of this session, Dr Albert Chan (Royal Columbian Hospital, New Westminster, BC), but at this point, it is only hypothesis generating, he stressed, speaking to heartwire .

Comoderator Dr Harindra Wijeysundera (Sunnybrook Health Sciences Centre, Toronto, ON) concurred. The treatment effect "is hard to believe," he added, noting that four studies are very few for a meta-analysis. "As the presenter stated, it lays the foundation as a hypothesis for more study," he said.

If the group does a prospective study that turns out to be positive, "certainly this [will be] another motivating factor to encourage people to get the flu vaccine," Chan said. "[That] study needs to target people at risk, not teenagers," he emphasized.

Flu Vaccine Might Decrease ICD Shocks

In another session, Dr Ramanan Kumareswaran (Sunnybrook Health Sciences Centre) presented study findings that suggested that among patients with implantable cardioverter defibrillators (ICDs), those who received the flu shot had fewer ICD shocks in the following flu season [2].

The researchers had invited all patients who presented at the Sunnybrook Hospital ICD clinic for follow-up between September 1, 2011 and November 31, 2011 to complete a survey asking whether they had received a flu shot the previous year. They then reviewed the patients' charts to determine the number of ICD shocks patients had received prior to and during the 2010–2011 flu season.

Of the 229 patients who completed the survey, 179 patients (78%) had gone for a flu shot. "Most patients could get [the influenza vaccine] easily," said Kumareswaran, noting that it is available at no cost to everyone living in Ontario.

A small number of patients--39 individuals (17%)--had received at least one ICD shock during the two study periods. There was a trend that fewer patients who had received the flu shot than patients who had not been inoculated subsequently had at least one ICD shock during the following flu season: 10.6% of patients vs 13.7% of patients (p=NS).

Study limitations are that it was a single-center study, the vaccination rate was based on self-reporting, and it was a small sample with a low event rate.

Although the trial needs to be replicated on a larger scale to see if the results are reproducible, nevertheless it suggests that "if there is a true decrease in ICD therapies, the influenza vaccine may lead to an increase in well-being" in patients who already have compromised survival, Kumareswaran said.

The researchers declared they had no conflict of interest.