Clinical trial NCT00607178: The Efficacy of Influenza Vaccine in Reducing Cardiovascular Events in Patients With Coronary Artery Diseases
Official title: Randomized, Single-Blind, Placebo-Controlled Study of Influenza Vaccine in Preventing Cardiovascular Events in Post-Myocardial Infarction Patients and in Those With Stable Angina Pectoris
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Coronary Artery Diseases
Myocardial Infarction
Stable Angina
Keywords: Influenza
Vaccine
Lead sponsor: Shahid Beheshti University of Medical Sciences
Sponsor class: OTHER
First posted: 2008-02-05
Enrollment: 300
Sex: ALL
Minimum age (years): 25
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Influenza vaccine reduces the cardiovascular events in post-myocardial infarction (MI) patients and in those with stable angina (SA).

Detailed description: A connection between infectious processes and atherosclerosis is repeatedly reported \[1\]. Acute respiratory infection was found to be associated with myocardial infarction (MI) \[2,3\] and a number of epidemiological studies found that mortality attributable to cardiovascular diseases is increased during influenza epidemics \[4\]. Naghavi et al \[5\] in a case-control study of patients with coronary artery disease (CAD) found that vaccination against influenza was negatively associated with the development of new MI during the same influenza season. While some clinical trials found influenza vaccine effective in secondary prevention of cardiovascular adverse events \[6,7\], a large trial \[8\] failed to approve such an efficacy. Furthermore, a recent review of published trials on the subject concluded that frailty selection bias and use of non-specific endpoints such as all cause mortality have led cohort studies to greatly exaggerate vaccine benefits and that the remaining evidence base is currently insufficient to indicate the magnitude of the mortality benefit of the vaccination program \[9\].

This study aims to assess the efficacy of vaccine in secondary prevention of cardiovascular events in MI and stable angina (SA) patients using specific endpoints including reliable quantitative tools.

Eligibility criteria: Inclusion Criteria:

* Patients with the diagnosis of acute, evolving or recent MI (after recovered the acute phase) as defined by:

  1. Typical rise and gradual fall (troponin) or more rapid rise and fall (CK-MB) of biochemical markers of myocardial necrosis with at least one of the following:

     * Ischemic symptoms
     * Development of pathologic Qwaves on the ECG
     * ECG changes indicative of ischemia (ST segment elevation or depression); OR
     * Coronary artery intervention (e.g., coronary angioplasty).
  2. Pathologic findings of an acute MI \[12\]
* Patients with stable angina pectoris and documented coronary artery stenosis (angiography).

Exclusion Criteria:

* Any acute disease
* Chronic liver or kidney diseases
* Conditions accompanied by immunosuppression (like organ transplantation, HIV)
* Diagnosed malignancy
* Incubation with influenza vaccine within the past 5 years
* Any psychological disease that interferes with regular follow-up
* Congestive heart failure (Killip class IV)
* Unstable angina, and contradictions of vaccine incubation (like egg allergy).

Primary outcomes:
measure: Cardiovascular death
timeFrame: 6 months
Secondary outcomes:
measure: Acute coronary syndrome (MI or unstable angina)
timeFrame: 6 months
measure: Admission for Coronary Artery Disease
timeFrame: 6 months
measure: Angina severity (Seattle Angina Questionnaire [10])
timeFrame: 6 months
measure: Coronary artery stenosis (modified Gensini score [11])
timeFrame: 6 months
measure: Coronary revascularization (artery bypass graft or percutaneous coronary intervention)
timeFrame: 6 months
measure: Influenza infection
timeFrame: 6 months
Other outcomes:
Locations:
city: Tehran
country: Iran, Islamic Republic of
facility: Shaheed Modarres Medical Center
Study officials:
affiliation: Infectious Diseases and Tropical Medicine Research Center, Shaheed Beheshti Medical University, Tehran, Iran
name: Maryam Keshtkar-Jahromi, M.D.; M.P.H.
role: STUDY_CHAIR
affiliation: Cardiovascular Research Center, Shaheed Beheshti Medical University, Tehran, Iran
name: Hossein Vakili, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Shahid Beheshti University of Medical Sciences
name: Ali Eskandari, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Shahid Beheshti University of Medical Sciences
name: Mohammad Rahnavardi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Shaheed Beheshti University (MC)
name: Sharareh Gholamin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Shaheed Beheshti University (MC)
name: Seyed Mostafa Razavi, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gurfinkel E, Lernoud V. The role of infection and immunity in atherosclerosis. Expert Rev Cardiovasc Ther. 2006 Jan;4(1):131-7. doi: 10.1586/14779072.4.1.131.
citation: Spodick DH, Flessas AP, Johnson MM. Association of acute respiratory symptoms with onset of acute myocardial infarction: prospective investigation of 150 consecutive patients and matched control patients. Am J Cardiol. 1984 Feb 1;53(4):481-2. doi: 10.1016/0002-9149(84)90016-x.
citation: Bainton D, Jones GR, Hole D. Influenza and ischaemic heart disease--a possible trigger for acute myocardial infarction? Int J Epidemiol. 1978 Sep;7(3):231-9. doi: 10.1093/ije/7.3.231.
citation: Gurevich VS. Influenza, autoimmunity and atherogenesis. Autoimmun Rev. 2005 Feb;4(2):101-5. doi: 10.1016/j.autrev.2004.10.006. Epub 2004 Nov 20.
citation: Naghavi M, Barlas Z, Siadaty S, Naguib S, Madjid M, Casscells W. Association of influenza vaccination and reduced risk of recurrent myocardial infarction. Circulation. 2000 Dec 19;102(25):3039-45. doi: 10.1161/01.cir.102.25.3039.
citation: Gurfinkel EP, de la Fuente RL, Mendiz O, Mautner B. Influenza vaccine pilot study in acute coronary syndromes and planned percutaneous coronary interventions: the FLU Vaccination Acute Coronary Syndromes (FLUVACS) Study. Circulation. 2002 May 7;105(18):2143-7. doi: 10.1161/01.cir.0000016182.85461.f4.
citation: Leon de la Fuente R, Gurfinkel EP, Toledo D, Mautner B; Grupo de Estudio FLUVACS. [Flu vaccination in patients with acute coronary syndromes: treatment benefit in prespecified subgroups]. Rev Esp Cardiol. 2003 Oct;56(10):949-54. doi: 10.1016/s0300-8932(03)76991-7. Spanish.
citation: Jackson LA, Yu O, Heckbert SR, Psaty BM, Malais D, Barlow WE, Thompson WW; Vaccine Safety Datalink Study Group. Influenza vaccination is not associated with a reduction in the risk of recurrent coronary events. Am J Epidemiol. 2002 Oct 1;156(7):634-40. doi: 10.1093/aje/kwf073.
citation: Simonsen L, Taylor RJ, Viboud C, Miller MA, Jackson LA. Mortality benefits of influenza vaccination in elderly people: an ongoing controversy. Lancet Infect Dis. 2007 Oct;7(10):658-66. doi: 10.1016/S1473-3099(07)70236-0.
citation: Spertus JA, Winder JA, Dewhurst TA, Deyo RA, Prodzinski J, McDonell M, Fihn SD. Development and evaluation of the Seattle Angina Questionnaire: a new functional status measure for coronary artery disease. J Am Coll Cardiol. 1995 Feb;25(2):333-41. doi: 10.1016/0735-1097(94)00397-9.
citation: Gensini GG. Coronary Angiography. Mount Kisco, NY: Futura Publishing Co; 1975.
citation: Alpert JS, Thygesen K, Antman E, Bassand JP. Myocardial infarction redefined--a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. J Am Coll Cardiol. 2000 Sep;36(3):959-69. doi: 10.1016/s0735-1097(00)00804-4.