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January 22, 1997JAMA

Effects of Acadesine on Myocardial Infarction, Stroke, and Death Following SurgeryA Meta-analysis of the 5 International Randomized Trials

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Why the study?

Does acadesine reduce perioperative myocardial infarction, stroke, and death in patients undergoing CABG surgery?

Population

4,043 patients undergoing coronary artery bypass graft surgery, pooled from 5 randomized clinical trials…

Comparison

Acadesine by intravenous infusion for 7… vs Placebo

Design

Meta-analysis, randomized, double-blind, placebo-controlled

Follow-up

through postoperative day 4

Authors

DMDennis T. ManganoCardiac Surgery

Discussion

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Overview

Acadesine may warrant perioperative use in CABG to lower MI risk; confirms benefit across 5 RCTs in this meta-analysis.

Key Points

  • To evaluate the effects of the purine nucleoside acadesine on fatal and nonfatal cardiovascular and cerebrovascular complications in patients undergoing coronary artery bypass graft surgery.
  • Conducted an individual patient data meta-analysis of 5 randomized, placebo-controlled, double-blind trials across 81 international medical centers in the United States, Canada, and Europe.
  • Evaluated 4043 CABG surgery patients randomized to receive either placebo (n=2031) or acadesine (0.1 mg/kg/min; n=2012) via a 7-hour continuous IV infusion and cardioplegia solution.
  • Analyzed clinical outcomes using both fixed-effects and random-effects general parametric models.
  • Acadesine significantly decreased perioperative myocardial infarction by 27% (OR, 0.69; 95% CI, 0.51-0.95; P=.02) and cardiac death through postoperative day 4 by 50% (OR, 0.52; 95% CI, 0.27-0.98; P=.04).
  • The composite endpoint of myocardial infarction, stroke, or cardiac death decreased by 26% (OR, 0.73; 95% CI, 0.57-0.93; P=.01), though cerebrovascular accident alone was not significantly reduced (OR, 0.69; 95% CI, 0.44-1.08; P=.10).
  • Secondary analysis showed an 89% reduction in cardiac death following myocardial infarction with acadesine (1.4% [1 death/71 MIs] vs 13.3% [13 deaths/98 MIs] with placebo; P=.003), along with a one-third reduction in ventricular-assistance device usage (P=.05).

Structured PICO

Does acadesine reduce perioperative myocardial infarction, stroke, and death in patients undergoing CABG surgery?

P
Population
4,043 patients undergoing coronary artery bypass graft (CABG) surgery, pooled from 5 randomized clinical trials across 81 international medical centers.
I
Intervention
Acadesine (0.1 mg/kg/min) by intravenous infusion for 7 continuous hours and via the cardioplegia solution
C
Comparator
Placebo
O
Outcome
Perioperative myocardial infarction (MI)hard clinical

In patients undergoing CABG surgery, perioperative administration of acadesine significantly reduces the incidence of early myocardial infarction and cardiac death.

Cite This Study

Dennis T. Mangano (1997) studied this question.

synapsesocial.com/papers/6a702bb2ce524a4339c3effbhttps://doi.org/10.1001/jama.1997.03540280063035
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1An Initial Multicenter, Randomized Controlled Trial on the Safety and Efficacy of Acadesine in Patients Undergoing Coronary Artery Bypass Graft Surgery1994 · 55 citations
  2. 2Sustained protection by acadesine against ischemia- and reperfusion-induced injury. Studies in the transplanted rat heart.1992 · 60 citations
  3. 3Cumulative Meta-Analysis of Therapeutic Trials for Myocardial Infarction1992 · 1,158 citations
  4. 4Progressive cardiac dysfunction with repeated pacing-induced ischemia: protection by AICA-riboside1991 · 18 citations
  5. 5A comparison of results of meta-analyses of randomized control trials and recommendations of clinical experts. Treatments for myocardial infarction1992 · 212 citations