CABG: acadesine given perioperatively prevented MI and cardiac death.

Clinical bottom line (level 2a)

  1. Patients given acadesine during coronary artery bypass surgery had fewer cardiovascular events (perioperative myocardial infarctions, strokes or cardiac deaths) (NNT = 52 at 4 days) .
Mangano : Journal of the American Medical Association 1997; 277 (4): 325-332
Expires June 2003

The study

Systematic review of five 'reasonably similar' double-blind randomised controlled trials of
  • Patients: undergoing coronary artery bypass surgery
  • Outcome: perioperative MI, diagnosed by new Q-waves on ECG and CK-MB changes or autopsy; cardiac death and stroke


    • Articles found in not stated using not stated, not stated (search terms: none given - presumed pharmaceutical database )

    Selection criteria: RCTs of acadesine vs placebo
    Appraisal criteria: none given
    Articles excluded if: none given

    5 studies had 4046 patients (mean age 63y, 79% male) for safety analysis, 4043 for stroke/cardiac death and 3993 for perioperative MI
    • Acadesine 0.1 mg/kg/min iv and cardioplegia solution 5 µg/ml Study drug was started 15 minutes before anaesthesia and continued for seven hours to immediate post-operative period. Cardioplegia solution also contained study drug.
    None formally stated, but one study (n=38) did not receive acadesine in the cardioplegia solution

    The evidence

    Outcome Time to outcome CER OR
    (95% CI)    		 NNT
    (95% CI)
    perioperative MI 4 days 98/2005
    (4.9%)    		 0.69
    (0.51 to 0.95)     		68
    (43 to 430)
    cardiac death 4 days 26/2031
    (1.3%)    		 0.52
    (0.27 to 0.98)     		160
    (110 to 3900)
    stroke 4 days 47/2031
    (2.3%)    		 0.68
    (0.44 to 1.08)     		140
    (NNT = 78 to infinity;
    NNH = 560 to infinity)
    MI, cardiac death or stroke 4 days 154/2031
    (7.6%)    		 0.73
    (0.57 to 0.93)     		52
    (32 to 200)

    • There was no significant difference noted between the two groups for adverse effects.

    Comments

    1. Regarding applicability the main and unsolvable obstacle is that, with almost absolute certainty, acadesine is not available.
    2. No attempt was made to identify other clinical trials.
    3. Acadesine is a purine nucleoside analogue that selectively raises tissue adenosine levels during ischaemic conditions.
    4. Perioperative beta-blockers have also shown to be beneficial in reducing perioperative MI.

    Citation

    1. Mangano DT, : Effects of acadesine on myocardial infarction, stroke and death following surgery: a meta-analysis of 5 international randomized trials. Journal of the American Medical Association 1997; 277 (4): 325-332
    Search Terms: angioplast* in Cochrane
    Contributor: Chris Ball and Clare Wotton, June 2000
    Reviewer: Luis Ruiz del Fresno

    Clinical Question.
    Patient undergoing coronary artery bypass surgery
    Intervention or Exposure acadesine
    Comparison placebo
    Outcome MI, cardiac death, stroke