Flu Shot Seen to Help Protect Diabetics From CV Hospitalizations

Marlene Busko

July 26, 2016

LONDON, UK — In a population of adults with type 2 diabetes seen in UK primary-care clinics, those who received the influenza shot had lower rates of hospitalization for flu and pneumonia, major cardiovascular diseases, and death during the following flu season compared with their unvaccinated peers[1].

The study by Dr Eszter P Vamos (Imperial College London, UK) and colleagues examined data from seven flu seasons from 2003–2004 to 2009–2010 and was published online July 25, 2016 in CMAJ.

The diabetic patients who received the flu shot had 15% to 30% lower rates of death or hospital admission for stroke, heart failure, pneumonia, or influenza (P <0.05) during the subsequent flu season.

Although many countries strongly recommend annual flu shots for older adults and patients with chronic conditions such as diabetes, evidence from small, less rigorous trials has not been compelling. This is the first study to look at specific cardiovascular outcomes in diabetic patients who did or did not receive a flu shot.

Influenza vaccine is largely underused among people with chronic diseases such as diabetes, Vamos told heartwire from Medscape. This study shows that it may significantly reduce cardiovascular illness and death during flu season, and thus it is very important for this high-risk population to get vaccinated, she stressed.

Dr Jacob A Udell (Peter Munk Cardiac Centre and Cardiovascular Division, University Health Network, and University of Toronto, ON), who was not involved with this study, agrees. These observational data provide "positive reinforcement of why we should be getting patients vaccinated, particularly patients who aren't over 65 but have diabetes," he told heartwire .

Before flu season starts, cardiologists, internists, and endocrinologists should ask their patients if they have received a flu shot, and if not, should offer it at their local sites. "I strongly believe it should be considered a performance measure in our system," similar to screening for high cholesterol, he added. This study shows "no harm and certainly potential benefit" if all adult diabetic patients get a flu shot. Moreover, "we shouldn't be satisfied with just a 65% vaccination rate," he said.

Udell is an investigator in the Influenza Vaccine to Effectively Stop Cardio Thoracic Events and Decompensated Heart Failure (INVESTED), which is just getting under way and will compare two newer types of influenza vaccines for protection from major heart and respiratory illness..

124,000 Diabetic Patients, Seven Flu Seasons

Vamos and colleagues aimed to compare the risk of hospitalization for major cardiovascular outcomes and death in flu season in patients with type 2 diabetes who did or did not receive a flu shot.

They also looked at influenza or pneumonia as a combined outcome, which is common in clinical trials since "influenza is often not detected or recognized as a trigger of severe events and remains profoundly underrecorded as a primary cause of illness on hospital admission records and mortality files," Vamos explained.

The researchers analyzed data from 300 primary-care practices in England that are part of a Clinical Practice Research Datalink. They identified 124,503 patients with type 2 diabetes over a 7-year period between 2003–2004 and 2009–2010.

The patients' vaccination uptake ranged from 63% in 2008–2009 to 69% in 2006–2007.

Compared with the other patients, those who received the flu shot were generally older, sicker, and taking more medications, but they had lower HbA1c and cholesterol levels.

Across these study years, there were 5142 hospital admissions for acute MI, 4515 admissions for stroke, 14,154 admissions for pneumonia or influenza, 12,915 admissions for heart failure, and 21,070 deaths.

After adjusting for covariates (age, sex, diabetes duration, number of comorbid conditions, smoking status, medications, blood pressure, body-mass index, HbA1c, cholesterol, hospital admissions, past influenza vaccination, pneumococcal vaccination, and cohort year) and residual confounding (calculated from the summer period when the vaccine should not provide benefit), they found that patients who had received the flu vaccination had significantly lower rates of all studied outcomes during the flu season, except for risk of acute MI.

Cardiovascular and Mortality Outcomes in Flu Season, Vaccinated vs Unvaccinated Diabetic Patients

Flu season outcome IRR (95% CI) P
Hospitalization for acute MI 0.81 (0.62–1.04) NS
Hospitalization for stroke 0.70 (0.53–0.91) <0.05
Hospitalization for heart failure 0.78 (0.65–0.92) <0.05
Hospitalization for pneumonia or influenza 0.85 (0.74–0.99) <0.05
All-cause death 0.76 (0.65–0.83) <0.05
IRR=incidence rate ratio, adjusted for multiple covariables and residual confounding
NS=not significant

The findings were similar after they excluded the 2 study years when there was not a good match between the vaccine and the circulating virus.

"Patients with diabetes . . . have a relatively suppressed immune system," so their immune system doesn't generate as good a response when they are infected with influenza, Udell noted, and the lower response in younger people with diabetes is similar to the age-associated decline in immune response.

The current study reinforces the importance of a flu shot in all patients with diabetes, he reiterated.

INVESTED Will Compare Trivalent vs Quadrivalent Vaccine, Two Doses

The current standard of care in the US and Canada is a trivalent vaccine with two strains of influenza A and one strain of influenza B, with 15 µg of each strain, Udell explained.

A quadrivalent vaccine with two strains of influenza A and two of influenza B, with 15 µg, has been approved by Health Canada and by the US Food and Drug Administration (FDA), and it is starting to come into use in the US and more slowly in Canada.

Moreover, he said, a high-dose trivalent vaccine with two influenza A strains and one influenza B strain with 60 µg of each strain has also been approved by the FDA and Health Canada, largely based on a recent trial[2], but it is not approved for adults under 65; in this age group, its use is investigational.

INVESTED will shed light on these two newer forms of flu vaccines in the general population, including diabetic patients, according to Udell. It will test the hypothesis that Fluzone (Sanofi Pasteur) high-dose trivalent influenza vaccine will reduce cardiopulmonary events to a greater extent than Fluzone standard-dose quadrivalent influenza vaccine in high-risk cardiovascular patients with a recent history of MI or heart failure.

The trial plans to enroll 9300 participants over a pilot season and three additional influenza seasons, and the primary end point will be a composite of all-cause mortality or cardiopulmonary hospitalization. Enrollment for the pilot phase will start in September 2016 at 40 sites across North America (about 15 sites in Canada), and the final results are expected in February 2021.

The study authors and Udell have no relevant financial relationships.

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