Am I Getting the Influenza Shot Too?: Influenza Vaccination as Post–Myocardial Infarction Care for the Prevention of Cardiovascular Events and Death
2021; Lippincott Williams & Wilkins; Volume: 144; Issue: 18 Linguagem: Inglês
10.1161/circulationaha.121.057534
ISSN1524-4539
AutoresErin D. Michos, Jacob A. Udell,
Tópico(s)Influenza Virus Research Studies
ResumoHomeCirculationVol. 144, No. 18Am I Getting the Influenza Shot Too?: Influenza Vaccination as Post–Myocardial Infarction Care for the Prevention of Cardiovascular Events and Death Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toFree AccessEditorialPDF/EPUBAm I Getting the Influenza Shot Too?: Influenza Vaccination as Post–Myocardial Infarction Care for the Prevention of Cardiovascular Events and Death Erin D. Michos, MD, MHS and Jacob A. Udell, MD, MPH Erin D. MichosErin D. Michos Correspondence to: Erin D. Michos, MD, MHS, Associate Professor of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Blalock 524-B, 600 N Wolfe St, Baltimore, MD 21287. Email E-mail Address: [email protected] https://orcid.org/0000-0002-5547-5084 Division of Cardiology, Johns Hopkins School of Medicine, Baltimore, MD (E.D.M.). and Jacob A. UdellJacob A. Udell https://orcid.org/0000-0001-7402-9584 Cardiovascular Division, Women's College Hospital and Peter Munk Cardiac Centre, Toronto General Hospital, University of Toronto, Ontario, Canada (J.A.U.). Originally published1 Nov 2021https://doi.org/10.1161/CIRCULATIONAHA.121.057534Circulation. 2021;144:1485–1488This article is a commentary on the followingInfluenza Vaccination After Myocardial Infarction: A Randomized, Double-Blind, Placebo-Controlled, Multicenter TrialAn ounce of prevention is worth a pound of cure.—Benjamin Franklin1Article, see p 1476The link between viral infections and acute cardiovascular complications has been well established.2 A viral-mediated inflammatory response can trigger acute plaque rupture leading to a type 1 myocardial infarction (MI) or induce global myocardial depression. Serious viral illness can also exacerbate underlying cardiovascular disease (CVD) and contribute to a type 2 MI through the increased metabolic demand conferred by fever, tachycardia, and hypoxemia.2,3 Moreover, patients with viral infections are vulnerable to developing opportunistic secondary bacterial infections that are also associated with cardiovascular risk. The cardiovascular complications associated with serious influenza are not trivial. In a study of US adults hospitalized with laboratory-confirmed influenza from 2010 to 2017, approximately 1 in 8 patients experienced an acute cardiovascular event, with 31% of those requiring intensive care and 7% eventually dying.4 Before the coronavirus disease 2019 (COVID-19) pandemic, in the 2018 to 2019 influenza season, an estimated 36 million persons in the United States were infected with influenza, nearly 500 000 were hospitalized, and >34 000 died.5To mitigate this risk, since 2006, the American Heart Association and the American College of Cardiology have recommended influenza vaccination for all patients with established coronary artery disease with a Class I recommendation (Level of Evidence B).6 This is similar to guidance from the Centers for Disease Control and Prevention that recommend annual influenza vaccination for all adults, with a stronger endorsement for individuals at high risk for severe illness from influenza and its associated complications, such as older adults ≥50 years of age; those with chronic conditions such as coronary artery disease, heart failure, and chronic lung disease; pregnant women; and household contacts of these high-risk patients and health care workers.7Yet, despite these long-standing recommendations, their uptake remains suboptimal. A 2016 to 2019 US-based survey found that only 50% of patients with atherosclerotic CVD received an influenza vaccination, with substantial disparities by race, ethnicity, and region,8 highlighting the socioeconomic determinants that are associated with the receipt of influenza vaccination. Similarly, between 2012 and 2017, 1 in every 3 patients hospitalized with heart failure were not vaccinated for influenza or pneumococcus in the American Heart Association Get With The Guidelines-Heart Failure program, without any sign of improvement over 5 years of study.9The evidence for benefit of influenza vaccination among individuals with CVD was already strong.10,11 In a previous meta-analysis including 4 randomized controlled trials and 12 observational studies, comprising almost 240 000 patients with CVD, the authors found that influenza vaccination was associated with a 28% and a 18% relative risk reduction in all-cause and cardiovascular mortality, respectively, and a 13% relative risk reduction in major adverse cardiovascular events over a median follow-up of 20 months.11 Although a recent trial did not find any difference in cardiopulmonary outcomes when comparing a high-dose trivalent versus a standard-dose quadrivalent inactivated influenza vaccine among high-risk patients with CVD,12 vaccination is still strongly indicated for these patients, without a clear preference for 1 type of vaccine over another.3However, there still remained some areas of uncertainty. For example, although serious vaccine-associated adverse events are exceedingly low, whether vaccination (which might generate a temporary, slight increase in heart rate and low-grade fever attributable to activation of an immune response) could be delivered safely in the post-MI period remained less well established. In addition, whether provision of an influenza vaccine early post-MI would lead to additional cardioprotection on top of contemporary standard of care was uncertain.The IAMI study (Influenza Vaccination After Myocardial Infarction) was a double-blind randomized controlled trial to test whether influenza vaccination given early after an admission for MI or high-risk coronary artery disease can reduce major adverse cardiovascular events (defined as a composite of all-cause death, MI, or stent thrombosis) within 12 months of the index event. IAMI enrolled 2571 participants from 30 centers across 8 countries between October 2016 and March 2020, before being stopped early by the Data Safety Monitoring Board because of the onset of the COVID-19 pandemic. The key findings, published by Fröbert et al13 in this issue of Circulation, were that influenza vaccination administered within 72 hours of an invasive coronary procedure or hospitalization with MI resulted in a 28% lower risk of major adverse cardiovascular events, a 41% reduction in cardiovascular mortality, and a 41% reduction in all-cause mortality. The findings for MI trended in a favorable direction but were not statistically significant, which may have been attributable to low numbers of events and limited statistical power. Findings for the primary outcome in IAMI were consistent by subgroups defined by sex, age (<65 versus ≥65 years), diabetes status, smoking status, previous MI, ST-segment–elevation MI versus non–ST-segment–elevation MI, and influenza season. There were no increased serious adverse events, confirming that influenza vaccination can be given safely in the immediate post-MI period. The authors also combined the IAMI results in a meta-analysis with 3 other trials and demonstrated a 49% reduction in cardiovascular death (pooled hazard ratio, 0.51 [95% CI, 0.36–0.71]).We congratulate the authors for undertaking this important study, and the findings should influence clinical practice, prompting an even stronger endorsement for influenza vaccination as part of routine post-MI care during influenza season. However, interpretation of the study findings should be noted with some caveats. For one, the study enrolled only 2571 individuals of the planned 4372, because it was terminated early. Early termination may exaggerate the estimates of the benefits of study drug. Second, similar to many other cardiovascular trials,14 there was an unfortunate underrepresentation of women, who comprised only 19% of participants, limiting the generalizability in that subgroup. Third, and most notably, all these patients would already be indicated for influenza vaccination by the aforementioned guidelines, which raised ethical implications of those assigned to placebo. However, the investigators only enrolled individuals who were not already vaccinated that season or planning to get vaccinated, and individuals were still allowed to pursue vaccination outside the trial if desired. Only 13% of individuals in the placebo group did cross over to vaccination, but this crossover would have only weakened, not strengthened the benefits seen.The observed 41% reduction in both all-cause and cardiovascular death is truly remarkable, especially when placed into context with other established secondary prevention pharmacological interventions such as β-blockers, statins, and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers that reduce the risk of reinfarction in the range of 20% to 25% post-MI (Figure).15-22 Nevertheless, despite having an even greater magnitude of benefit for risk reduction, influenza vaccination has not been given the same level of attention or priority as a secondary prevention strategy. Although it should be acknowledged that relative risk reductions for different pharmacotherapies cannot be directly compared across studies given different study designs and background risk of study populations, it should also be noted that the patients in IAMI were very well treated with contemporary medical therapy at discharge post-MI, with 98% on aspirin, 97% on P2Y12 inhibitor, 70% on angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, 78% on β-blockers, and 98% on statins; the benefit of influenza vaccine was incremental to that.Download figureDownload PowerPointFigure. Cumulative impact of evidence based medical therapies after myocardial infarction on all-cause or cardiovascular mortality. Lytics: 17 187 patients with acute myocardial infarction (MI) in ISIS-2 trial (Second International Study of Infarct Survival). Follow-up of 5 weeks. Vascular death events: aspirin+thrombolysis (8%) versus Control (13.2%), for a 42% risk reduction (odds ratio, 0.58 [95% CI, 0.50–0.66]).16 Primary PCI: 7720 patients with ST-segment–elevation MI in a meta-analysis. Follow-up through 30 days. All-cause death events: primary PCI; (7%) versus thrombolysis (9%), for a 27% risk reduction (odds ratio, 0.73 [95% CI, 0.62–0.86]).17 β-Blockers: BHAT (Beta-Blocker Heart Attack Trial; Unique identifier: NCT00000492) of 3837 patients post-MI. Follow-up 25 months. Cardiovascular death rates: 6.6% (propranolol) versus 8.9% (placebo) for 26% risk reduction.18 Similar reduction in a meta-analysis of 24 974 patients with acute MI in a meta-analysis. Follow-up 6 to 48 months. All-cause death for β-blocker versus placebo, 23% risk reduction (odds ratio, 0.77 [95% CI, 0.69–0.85]).19 ACE inhibitors: Among 5966 patients from the SAVE (Survival and Ventricular Enlargement), AIRE (Acute Infarction Ramipril Efficacy), and TRACE (Trandolapril Cardiac Evaluation) trials post-MI, all-cause death at 1 year: 15.3% for ACE inhibitors versus 17.6% for placebo for 16% risk reduction (odds ratio, 0.84 [95% CI, 0.73–0.97]).20 P2Y12 inhibitors: 12 562 patients with acute coronary syndrome in the CURE trial (Clopidogrel in Unstable Angina to Prevent Recurrent Events). Mean follow-up 9 months. Cardiovascular death events: clopidogrel (5.1%) versus placebo (5.5%), for a nonsignificant 7% risk reduction (RR, 0.93 [95% CI, 0.79–1.08]).21 Statins: 26 491 patients after acute coronary syndrome in a meta-analysis. Follow-up 1 year. Cardiovascular mortality events: high-intensity statin (2.7%) versus placebo (3.6%), for a 24% risk reduction (RR, 0.76 [95% CI, 0.60–0.96]).22 Influenza vaccine: 2571 patients post-MI or admission with high-risk coronary artery disease. Follow-up 1 year. Cardiovascular death events: vaccine (2.7%) versus placebo (4.5%), for a 41% risk reduction (hazard ratio, 0.59 [95% CI, 0.39–0.90]). (IAMI trial [Influenza Vaccination After Myocardial Infarction]: NCT02831608) ACEi indicates angiotensin-converting enzyme inhibitors; ASA, aspirin; and PCI, percutaneous coronary intervention.The mechanisms behind such a remarkable cardiovascular benefit may be multifactorial. In addition to preventing influenza infection and avoiding the metabolic stressors of a serious virus-associated illness, it has also been theorized that the vaccination process itself may interact with immune and inflammatory systems to promote plaque stabilization. Indeed, in the IAMI trial, it was demonstrated that the time-to-event curves for vaccination versus placebo separated early after the index hospitalization and then stabilized around 3 months, supporting more immediate benefits from vaccination. Whether this early benefit is through dampening of the inflammatory response and stabilization of plaque in the immediate aftermath of an acute MI is uncertain.The findings of IAMI support and even strengthen the existing American Heart Association/American College of Cardiology Guideline recommendations already in place,5 which perhaps could move from a Class I (Level of Evidence B) to a Class I (Level of Evidence A) given the consistency of trial results across multiple randomized controlled trials. After the IAMI trial, there should be new implementation strategies put in place, such as adding influenza vaccination to the post-MI checklist, along with their statins, β-blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and lifestyle recommendations. All patients post-MI should be offered vaccination in the hospital before discharge, if not already vaccinated that season, and its provision potentially measured as a care performance metric. Receipt of vaccination could also be double-checked/confirmed on enrollment to cardiac rehabilitation. Influenza vaccination can be coadministered with the COVID-19 vaccination, if not already received.23 Because acute cardiovascular events have also been demonstrated with COVID-19 infection, COVID-19 vaccination is also strongly recommended for patients with or at risk for CVD.23As Benjamin Franklin said, "An ounce of prevention is worth a pound of cure."1 It is time to change the thinking around vaccination as just being a prevention strategy for the avoidance of viral illness but as a prevention strategy for avoidance of cardiovascular morbidity and mortality. Often vaccination is relegated to the domain of primary care with the hope that it gets done. But, given the suboptimal uptake of influenza vaccine among patients with CVD, cardiologists should take greater ownership to ensure their patients receive this important, guideline-recommended cardiovascular preventive strategy in the same fashion as other prevention strategies such as statins. As part of a team-based approach to care, this should also fall within the scope of practice for cardiologists to provide influenza vaccines to their high-risk patients with CVD, essentially an annual vaccination against cardiovascular outcomes.Article InformationSources of FundingNone.Disclosures Unrelated to this work, Dr Michos has served on advisory boards for Novo Nordisk, Bayer, Amarin, AstraZeneca, Esperion, and Novartis. Dr Udell has served as a consultant or speaker for AstraZeneca, Bayer, Boehringer Ingelheim-Lilly, Janssen, Merck, Novartis, and Sanofi and has received research grants from AstraZeneca, Amgen, Bayer, Boehringer Ingelheim-Lilly, and Janssen.Footnoteshttps://www.ahajournals.org/journal/circThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.For Sources of Funding and Disclosures, see page 1488.Correspondence to: Erin D. 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Circulation. 2021;144:1476-1484 November 2, 2021Vol 144, Issue 18Article InformationMetrics Download: 445 © 2021 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.121.057534PMID: 34723637 Originally publishedNovember 1, 2021 Keywordsheart disease risk factorsmyocardial infarctioninfluenza vaccinescardiovascular diseasesinfluenza, humanEditorialsPDF download Advertisement SubjectsSecondary Prevention
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