Oseltamivir Protective Against Influenza Induced Cardiac Events
By Amesh A. Adalja, MD, April 3, 2009
When given at the appropriate time and barring resistance, antiviral therapy is known to lessen symptoms, shorten hospitalizations, and reduce respiratory complications of influenza infections in humans. A new study finds that it can also reduce cardiovascular complications following influenza infection in patients with previous cardiac disease.
In people, human-adapted influenza viruses replicate primarily in the respiratory tract; however, this local infection produces systemic disease related to the intense immune response and possible viremia. Cardiac complications such as pericarditis and myocarditis are frequently encountered, and increased hospitalization rates for cardiovascular events such as stroke, myocardial infarction, angina, and sudden cardiac death have been reported during influenza epidemics as well.1 Evidence has accumulated indicating that antiviral treatment, along with vaccination, may protect against the occurrence of cardiovascular complications.1
Recurrent Cardiovascular Events Monitored
In a study published in Circulation: Cardiovascular Quality Outcomes, Casscells and colleagues analyzed data from more than 36,000 individuals with influenza to ascertain the relationship between cardiovascular outcomes and receipt of the antiviral medication oseltamivir.1
Utilizing the U.S. Department of Defense’s TRICARE Program,* the authors examined records for those members who had a prior diagnosis of cardiovascular disease (myocardial infarction, angina pectoris, heart failure, stroke, a history of angioplasty, or coronary artery bypass) and a subsequent diagnosis of influenza between 2003–2007. Of those with a history of cardiovascular disease and influenza infection, records for the 30 day period after influenza diagnosis were analyzed for adverse cardiovascular outcomes (myocardial infarction, stroke, angina pectoris, and sudden cardiac arrest). Outcomes for patients who were and were not prescribed oseltamivir were compared. Patients who received zanamivir and who filled their prescription outside the 2-day window for maximal effectiveness were excluded.1
Event Rate More Than Double in Untreated Subjects
The authors identified 37,482 study subjects who had a history of cardiovascular disease and a subsequent diagnosis of influenza; of those, 6,771 were prescribed oseltamivir. Of note, there were more subjects prescribed anti-lipid agents in the oseltamivir group (34.3% vs. 28.8%, P<0.005).1
The authors report that the incidence of cardiovascular outcomes was significantly higher in the untreated group (21.1% vs. 8.6%), and that all 4 individual outcomes (myocardial infarction, stroke, sudden cardiac death, heart failure, and angina) were significantly higher in the untreated group. Also, the mean days to event were significantly reduced amongst those not treated (8.1 vs. 12.7 days). A propensity-score weighted regression analysis, utilized to minimize bias that may have occurred in antiviral treatment decisions, yielded a significant protective effect (OR 0.417) of oseltamivir treatment. Receipt of anti-lipid agents was not a significant predictor of cardiovascular events in this model.1
Antiviral Therapy Should Be Strongly Advocated
This study provides more evidence of the benefits of antiviral treatment for seasonal influenza, which causes 36,000 deaths per year in the U.S. Reducing all types of morbidity through expeditious treatment of influenza is a key component of a comprehensive approach to both seasonal and pandemic influenza. As recent studies have shown, antiviral therapy is underutilized, and studies that show benefits of antiviral therapy beyond symptomatic relief are an important factor that should be weighed when prescribing antivirals.2 Given the almost universal resistance to oseltamivir among current influenza A H1N1 isolates, it is reassuring to know that similar cardiovascular benefits have been demonstrated with other influenza antivirals.3,4
*The TRICARE program is a component of the Military Health System that encompasses active duty service members, retirees, and their dependents.
Casscells SW, Granger E, Kreiss AM, et al. Use of oseltamivir after influenza infection as associated with reduced incidence of recurrent adverse cardiovascular outcomes among military health system beneficiaries with prior cardiovascular diseases. Circ Cardiovasc Qual Outcomes 2009; 2: 108-115. http://www.tiny.cc/PLATT. Accessed April 2, 2009.
Wilkes JJ, Zaoutis TE, Keren R, et al. Treatment with oseltamivir in children hospitalized with community-acquired, laboratory-confirmed influenza: Review of five seasons and evaluation of an electronic reminder. Journal of Hospital Medicine 2009; 4: 171-178. http://tiny.cc/wSgFk. Accessed April 2, 2009.
Enger C, Nordstrom BL, Takrar B, et al. Health outcomes among patients receiving oseltamivir. Pharmacoepideiol Drug Saf 2004; 13: 227-237. http://tiny.cc/iFQcP. Accessed April 2, 2009.
Dharan NJ, Gubareva LV, Meyer JJ, et al. Infections with oseltamivir-resistant influenza A(H1N1) virus in the United States. JAMA 2009;301: 1034-41. http://tiny.cc/VgVqW. Accessed April 2, 2009.