Influenza Vaccination in Prevention From Acute Coronary Events in Coronary Artery Disease - FLUCAD Study
Condition: Coronary Artery Disease
MeSH terms: Influenza, Human; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      Background: Influenza vaccination is recommended in patients (pts) with cardiovascular
      disease, however there is a shortage of clinical studies proving its protective effect on
      clinical course of coronary artery disease (CAD). The aim of the study was to evaluate the
      effect of influenza vaccination on the incidence of coronary events in pts with CAD confirmed
      by coronary angiography.
    

Detailed description: 
      A possible relation between influenza and higher mortality from cardiovascular problems was
      first noticed in early nineteen hundreds, after epidemics in Europe and United States were
      discovered (1). In the last decade many studies implicating an important role of inflammation
      and infection (Herpes virus, Chlamydia pneumoniae, Helicobacter pylori) in development and
      progression of atherosclerosis (2,3), and markers of inflammation like: hs-CRP, fibrinogen,
      have become new independent cardiovascular risk factors (4).

      Many general physicians now recommend influenza vaccination in patients with coronary artery
      disease (CAD) despite shortage of studies proving its protective effect on clinical course of
      CAD. In literature we found only a few reports exploring the hypothesis that influenza
      vaccination might reduce the incidence of myocardial infarction (MI) and acute coronary
      syndromes (ACS).

      Naghavi et all. in retrospective, case- control study of 218 patients with chronic coronary
      disease reported that influenza vaccination was strongly associated with freedom from new MI
      during the same influenza season. (OR 0.33, 95% CI 0.13 to0.82, p=0.017) (5). Gurfinkiel et
      all. evaluated in prospective, single- blind Fluvacs study that preventive impact of
      vaccination on subsequent ischemic events at 6 months follow-up. Study group consisted of 301
      patients after coronary angioplasty (PCI). The first primary outcome- cardiovascular death
      occurred in 2% in vaccine group compared with 8% in the control group (p=0.01) and triple
      composite end point (death, myocardial infarction and hospitalization from ischemia occurred
      in 11% in vaccine group vs. 23% in controls (p=0.0009) (6). In the contrary, Jackson et all.
      in largest study of 1378 survivors of first MI, in long (median 2.3 year) follow-up didn't
      find the benefit of influenza vaccine on the protection against recurrent coronary events
      (7).

      The aim of our study is to evaluate the influence of influenza vaccination on the incidence
      of cardiac events (cardiovascular death, myocardial infarction, acute coronary syndromes,
      coronary revascularization and hospitalizations from ischemia) in patients with
      angiographically confirmed coronary disease.

      References:

        1. Collins SD. Excess mortality from causes other that influenza and pneumonia during
           influenza epidemics. Public Health Rep. 1932;47:2159-80.

        2. Sorlie PD, Adam E, Melnick SL, et al. Cytomegalovirus/herpesvirus and carotid
           atherosclerosis: the ARIC Study. J Med Virol. 1994;42:33-37.

        3. Zhou YF, Wanishsawad C, Epstein SE. Chlamydia pneumonia-induced transaction of
           cytomegalovirus: potential synergy of infectious agents in the pathogenesis of
           atherosclerosis. J Am Coll Cardiol. 1999;33(suppl A):260A.

        4. Toss H, Lindahl B, Siegbahn A, Wallentin L. (Frisc study group). Prognostic Influence of
           Increased Fibrinogen and C- reactive Protein Levels in Unstable Coronary Artery Disease.
           Circulation 1997; 96: 4304- 4210.

        5. Naghavi M., Barlas Z., Siadaty S., Nagiub S., Madjid M., Casscells W.: Association of
           influenza vaccination and reduced risk of myocardial infarction Circulation 2000;
           102:3039-3045.

        6. Gurfinkel E.P., Leon de la Fuente R., Mendiz O., Mautner B. For the FLUVACS Study Group:
           Influenza vaccine pilot study in acute coronary syndromes and planned percutaneous
           coronary interventions. The FLU vaccination acute coronary syndromes (FLUVACS) Study.
           Circulation 2002;105:2143-2147.

        7. Jackson L.A., Heckbert S.R., Psaty B.M., Malais D., Barlow W.E., Thompson W.W. Vaccine
           Safety Datalink Study Group: Influenza vaccination is not associated with a reduction in
           the risk of recurrent coronary events. Am. J. Epidemiol. 2002; 156: 634-40.
    

Intervention name(s): Influenza vaccination: Influvac (SolvayPharma); placebo influenza vaccine
Intervention type(s): Biological; Biological
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: influenza vaccination; coronary artery disease; prevention; acute coronary syndromes