Most Patients With Heart Failure Are Missing the Boat on Flu, Pneumococcal Vaccines

Despite evidence suggesting that vaccination against respiratory infections improves cardiovascular outcomes in patients with heart failure, not to mention supportive guideline recommendations, coverage rates remain woefully low in this population, a review shows.

A recent analysis of the PARADIGM-HF trial conducted in North and South America, Asia, and Europe among patients who had chronic heart failure with reduced ejection fraction showed that just 21% received flu vaccine. The rate was higher in the United States (55%) but that still trailed behind several other Western nations.

Consistent with those low numbers, a study conducted at a single center in Florida found flu and pneumococcal immunization rates of just 28.3% and 30.7%, respectively, in patients with reduced LVEF.

Ankeet Bhatt, MD (Duke University Medical Center, Durham, NC), lead author of the review, said part of the reason for the poor coverage rates is that the medical community has not figured out the best way to implement vaccination in patients with heart failure. It’s unclear whether the effort should be made in the inpatient or outpatient setting and whether primary care physicians or cardiologists should take the lead, he said.

“We know there are clear benefits to using both pneumococcal and influenza vaccination in patients with heart failure,” Bhatt told TCTMD. “I think we should look at the way we implement vaccinations and perhaps we can get some more insight into why vaccination rates are so low and then change the way our systems are developed to promote higher rates.”

Jacob Udell, MD (University of Toronto, Canada), who was not involved in the review, called the low immunization rates “abysmal” and said the blame can be spread around. “I don’t think providers are doing a fantastic job of reminding patients that it’s standard of care,” he told TCTMD. “We can certainly do better.”

But Udell also said the suboptimal rates can be partially attributed to a prevailing skepticism in the public about whether vaccinations are needed. Heart failure itself does not represent a contraindication to vaccination, although those who are acutely decompensated probably should not receive a shot, he added. This would also likely apply to patients with other conditions who are unstable.

But for patients with heart failure, Udell said, “There’s very little reason why you shouldn’t be getting a vaccine every year.”

Respiratory Infections Spark Heart Failure Exacerbations

One reason for looking at the effects of immunization in patients with heart failure is that vaccination has been shown in other chronic disease settings to be an effective, low-cost intervention to improve outcomes, said Bhatt.

Vaccination against flu and pneumococcal disease may be particularly important, he said, because of the strong association between respiratory infections and heart failure exacerbations. Thus, those vaccines may improve overall heart failure outcomes by reducing the frequency or severity of respiratory infections, he and his coauthors write in a paper published online February 1, 2017, ahead of print in JACC: Heart Failure.

Their review of the literature revealed, however, that those ideas have not been well studied in patients with heart failure, even though the Centers for Disease Control and Prevention  and several professional societies recommend yearly flu vaccination in patients with chronic cardiovascular disease, including heart failure.

There is some evidence from randomized trials and epidemiological studies to suggest that protecting against flu improves outcomes in elderly patients and those with ACS, but there have been no randomized trials comparing flu vaccination and placebo exclusively in patients with heart failure. Data on the effects of pneumococcal vaccination in that population are even more limited.

Yet, it is biologically plausible that protecting against flu and pneumococcal disease would have cardiovascular benefits, according to the authors, who point to preclinical studies showing that inflammatory processes associated with respiratory infections may accelerate atherogenesis or impair myocardial contractility.

“A direct link between vaccination-induced reduction in atherogenesis and the [heart failure] phenotype is not yet clearly established, though it would be theorized to reduce the incidence and progression of ischemic cardiomyopathy,” they write. “Given these proposed mechanisms, further investigation should be conducted to understand differential responses to vaccination in those with ischemic versus nonischemic cardiomyopathy.”

The Holy Grail of ‘Heart Disease Vaccines’

The reviewers say there are many opportunities for research across basic, translational, and clinical realms—looking at optimal timing and dosing and ways to improve vaccination rates, for example—and they give their support to a large, multicenter trial to evaluate the impact of respiratory vaccination in patients with heart failure.

Just such a trial is currently recruiting patients in North America. With a planned enrollment of 9,300 patients, INVESTED is investigating whether high-dose flu vaccine will improve outcomes in patients with a recent history of hospitalization for MI or heart failure compared with a standard dose. The primary endpoint is a composite of all-cause mortality or cardiopulmonary hospitalization.

“The Holy Grail has always been whether these vaccines that can protect us against infectious illness can really act as heart disease vaccines, [whether] ultimately these can be protective from triggering heart attacks, congestive heart failure, and death from cardiovascular complications,” said Udell, who is the Canada co-principal investigator for the trial.