Effects of acadesine on myocardial infarction, stroke, and death following surgery. A meta-analysis of the 5 international randomized trials. The Multicenter Study of Perioperative Ischemia (McSPI) Research Group
D. T. Mangano
Department of Anesthesiology, Multicenter Study of Perioperative Ischemia, San Francisco, CA 94134, USA.
OBJECTIVE: To determine the effects of a purine nucleoside, acadesine, on
the incidence of fatal and nonfatal cardiovascular and cerebrovascular
complications following coronary artery bypass graft (CABG) surgery. DATA
SOURCES: Individual patient data from 5 randomized, placebo-controlled,
double-blind clinical trials, including 81 international medical centers of
the United States, Canada, and Europe. STUDY SELECTION: All patients from
all clinical trials were included: a total of 4043 patients undergoing CABG
surgery, evaluable for efficacy, and randomized to receive either placebo
(n= 2031) or acadesine (0.1 mg x kg(-1) x min(-1); n=2012) by intravenous
infusion for 7 continuous hours and via the cardioplegia solution. DATA
EXTRACTION: Individual patient data were collected prospectively using
standardized forms and methods and double-data entry. A general parametric
approach and analysis-by-patient meta-analysis were used, including both
fixed effects and random effects models. Inclusion and exclusion criteria,
general methodology, and outcome assessment techniques were similar for all
trials. DATA SYNTHESIS: Acadesine decreased the incidence of the primary
outcome, perioperative myocardial infarction (MI) by 27% (odds ratio [OR],
0.69; 95% confidence interval [CI], 0.51-0.95; P=.02), decreased the
incidence of cardiac death through postoperative day 4 by 50% (OR, 0.52;
95% Cl, 0.27-0.98; P=.04), and decreased the incidence of combined outcome
(MI, stroke, or cardiac death) by 26% (OR, 0.73; 95% Cl, 0.57-0.93; P=.01).
The random effects models for these outcomes also yielded significant
results. The incidence of cerebrovascular accident was not significantly
reduced by acadesine (OR, 0.69; 95% Cl, 0.44-1.08; P=.10). A secondary
analysis of cardiac death following MI through postoperative day 4
demonstrated that acadesine decreased by 89% the number of deaths from
13.3% (13 deaths/98 MIs) in the placebo group to 1.4% (1 death/71 MIs) in
acadesine-treated patients (P=.003). Acadesine also reduced the use of
ventricular-assistance devices for severe postoperative heart failure by
approximately one third (P=.05). Finally, regarding safety, the incidence
of adverse events was similar in the acadesine vs placebo groups, with the
exception of a transient increase in serum uric acid in the acadesine
group. CONCLUSIONS: The results of this meta-analysis indicate that in
patients undergoing CABG surgery, treatment with acadesine before and
during surgery can reduce early cardiac death, MI, and combined adverse
cardiovascular outcomes.
Efficacy and Safety of Pyridoxal 5'-Phosphate (MC-1) in High-Risk Patients Undergoing Coronary Artery Bypass Graft Surgery: The MEND-CABG II Randomized Clinical Trial
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ABSTRACT
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Acadesine activates AMPK and induces apoptosis in B-cell chronic lymphocytic leukemia cells but not in T lymphocytes
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ABSTRACT
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ABSTRACT
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ABSTRACT
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ACADESINE MAY REDUCE COMPLICATIONS AFTER CABG
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