Wednesday, October 23, 2013

JAMA: Flu Vaccine and Cardiovascular Outcomes



# 7890


One of the problems with determining the true burden of influenza on the public’s health is that influenza is rarely listed as the primary cause of death when a patient dies with a history of other co-morbidities like coronary artery disease, Asthma, Diabetes, or COPD.   Yet we know that during the winter months, when influenza and other respiratory viruses are at their height – overall mortality goes up. 


Roughly 15 years ago, a study looked at the rate of heart attacks in the United States, and found that Acute Myocardial Infarctions (AMIs) run as much 53% higher during the winter months than than during the summer. While cold weather combined with strenuous physical activity (like clearing snow from sidewalks) have often been blamed for this spike, even in balmy Southern California, studies have shown a 33% increase in heart attacks over the holidays (cite).


Although not the first to do so, a year ago  in Study: Influenza And Heart Attacks, we looked at research that appeared in the Journal of Infectious Diseases that suggested Influenza - and other acute respiratory infections - can act as a trigger for heart attacks.  

Despite often disappointing vaccine effectiveness (VE) numbers for those over the age of 65 (see NFID: The Challenges Of Influenza In Older Adults), in recent years we’ve seen a series of studies that have suggested that the flu vaccine may be partially protective against heart attacks. 


In 2010 we saw a study in the CMAJ: Flu Vaccinations Reduce Heart Attack Risk that found that those over the age of 40 who get a seasonal flu vaccine each year may reduce their risk of a heart attack by as much as 19%. Almost immediately questions were raised over the way this study was conducted (see Vaccine/Heart Attack Study Questioned). The primary concern was these researchers only looked at heart attacks during `flu season’, without the control of looking at AMI risks year-round.


Just last August (see Study: Flu Vaccine May Reduce Heart Attack Risk), we looked at a new study out of Australia – published in the BMJ Journal Heart, that found compelling – but not exactly conclusive – evidence that flu shots may reduce the risk of heart attacks.


Today, another study, which appears in JAMA, that performed a meta-analysis of  5 published and 1 unpublished randomized clinical trials involving  6735 patients - some of whom received a flu shot while others received a placebo - and calculated the number of cardiac events each group suffered in the months that followed. 


Among those who had previously had a heart attack, the receipt of a flu vaccine was linked to a 55% reduction in having another major cardiac event in the next few months.


First a link to the JAMA study, and then some excerpts from the press release from  Women's College Hospital at the University of Toronto:


Association Between Influenza Vaccination and Cardiovascular Outcomes in High-Risk Patients

A Meta-analysis


Jacob A. Udell, MD, MPH, FRCPC1; Rami Zawi, MD2; Deepak L. Bhatt, MD, MPH3,4; Maryam Keshtkar-Jahromi, MD, MPH5,6; Fiona Gaughran, MD7,8; Arintaya Phrommintikul, MD9; Andrzej Ciszewski, MD10; Hossein Vakili, MD11; Elaine B. Hoffman, PhD4; Michael E. Farkouh, MD, MSc, FRCPC12; Christopher P. Cannon, MD4

Results Five published and 1 unpublished randomized clinical trials of 6735 patients (mean age, 67 years; 51.3% women; 36.2% with a cardiac history; mean follow-up time, 7.9 months) were included. Influenza vaccine was associated with a lower risk of composite cardiovascular events (2.9% vs 4.7%; RR, 0.64 [95% CI, 0.48-0.86], P = .003) in published trials. A treatment interaction was detected between patients with (RR, 0.45 [95% CI, 0.32-0.63]) and without (RR, 0.94 [95% CI, 0.55-1.61]) recent ACS (P for interaction = .02). Results were similar with the addition of unpublished data.

Conclusions and Relevance In a meta-analysis of RCTs, the use of influenza vaccine was associated with a lower risk of major adverse cardiovascular events. The greatest treatment effect was seen among the highest-risk patients with more active coronary disease. A large, adequately powered, multicenter trial is warranted to address these findings and assess individual cardiovascular end points.



From the press release:

Flu shot halves risk of heart attack or stroke in people with history of heart attack, study finds

TORONTO, ON, October 22, 2013 — The flu vaccine may not only ward off serious complications from influenza, it may also reduce the risk of heart attack or stroke by more than 50 per cent among those who have had a heart attack, according to new research led by Dr. Jacob Udell, a cardiologist at Women's College Hospital and clinician-scientist at the University of Toronto. What's more, the vaccine's heart protective effects may be even greater among those who receive a more potent vaccine.

"Our study provides solid evidence that the flu shot helps prevent heart disease in vulnerable patients —with the best protection in the highest risk patients," Dr. Udell said. "These findings are extraordinary given the potential for this vaccine to serve as yearly preventative therapy for patients with heart disease, the leading cause of death among men and women in North America."

Published today in the Journal of the American Medical Association, the study reviewed six clinical trials on heart health in people who received the flu vaccine. The studies included more than 6,700 patients with a history of heart disease. The researchers found people who received the flu shot:

  • Had a 36 percent lower risk of a major cardiac event (heart attack, stroke, heart failure, or death from cardiac–related causes) one year later
  • Had a 55 percent lower risk of a major cardiac event if they had a recent heart attack
  • Were less likely to die from cardiac-related and other causes, and
  • Were less likely to have a major cardiac event with a more potent vaccine compared with the standard seasonal vaccine

(Continue . . .)


While not a slam dunk (larger, more robust more studies are needed), this latest report adds to the body of evidence suggesting that influenza contributes significantly to cardiovascular events, and that flu vaccines may be useful in reducing cardiac mortality rates. 

I’m fully cognizant of the limitations of today’s flu vaccines, and try not to `oversell’  them in this blog. Nevertheless, I get one every year and urge that others do the same.


Not because they are 100% protective.  They aren’t. But they do offer moderate levels of protection (see CIDRAP: A Comprehensive Flu Vaccine Effectiveness Meta-Analysis), and have an excellent safety profile. 


We take sensible precautions every day – like buckling up when we drive, or wearing a helmet when we bike. None of these provide a 100% guarantee of avoiding injury, but they make sense because they increase our odds of walking away from an accident.   


I view getting a yearly flu shot in much the same way.