The Efficacy of Influenza Vaccine in Reducing Cardiovascular Events in Patients With Coronary Artery Diseases

Study Overview
=================
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.

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

Conditions
-----------------
Coronary Artery Diseases, Myocardial Infarction, Stable Angina

Intervention / Treatment
-----------------
* Biological: influenza vaccine
* Biological: placebo for influenza vaccine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with the diagnosis of acute, evolving or recent MI (after recovered the acute phase) as defined by: 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). 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).

Ages Eligible for Study
-----------------
Minimum Age: 25 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Influenza vaccine<br>Enrolled patients who are randomly assigned to receive influenza vaccine | Biological: influenza vaccine<br>* Intramuscular injection of one 0.5-mL dose of influenza vaccine<br>* Other names: 2006-2007 vaccination campaign of Influvac (SolvayPharma);|
| Placebo Comparator: Placebo<br>Enrolled patients who are randomly assigned to receive placebo of influenza vaccine | Biological: placebo for influenza vaccine<br>* Intramuscular injection of one 0.5-mL dose of placebo for influenza vaccine<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiovascular death |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute coronary syndrome (MI or unstable angina) |  | 6 months | 
| Admission for Coronary Artery Disease |  | 6 months | 
| Angina severity (Seattle Angina Questionnaire [10]) |  | 6 months | 
| Coronary artery stenosis (modified Gensini score [11]) |  | 6 months | 
| Coronary revascularization (artery bypass graft or percutaneous coronary intervention) |  | 6 months | 
| Influenza infection |  | 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Influenza, Vaccine