Pharmacologic Myocardial Protection in Patients Undergoing Noncardiac Surgery: A Quantitative Systematic Review

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Abstract
A number of drugs have been tested in clinical trials to decrease cardiac complications in patients undergoing noncardiac surgery. To compare the results of these studies, we conducted a quantitative systematic review. Medline, Embase, and Cochrane databases were searched for randomized trials that assessed myocardial ischemia, myocardial infarction, 30-day cardiac mortality, and adverse effects. Data were combined using a fixed-effect model and expressed as Peto odds ratios (OR) with 95% confidence interval (CI) and as numbers-needed-to-treat/harm (NNT/H). Twenty-one trials involving 3646 patients were included: 11 trials using beta-blockers (6 drugs; 866 patients), 6 clonidine or mivazerol (614 patients), 3 diltiazem or verapamil (121 patients), and 1 nitroglycerin (45 patients). All trials had an inactive control; there were no direct comparisons. beta-blockers decreased ischemic episodes during surgery (7.6% versus 20.2% with placebo; OR 0.32 [95% CI, 0.17-0.58]; NNT 8) and after surgery (15.2% versus 27.9% with control; OR 0.46 [95% CI, 0.26-0.81]; NNT 8). alpha(2)-agonists decreased ischemia during surgery only (19.4% versus 32.8%; OR 0.47 [95% CI, 0.33-0.68]; NNT 7). beta-blockers reduced the risk of myocardial infarction (0.9% versus 5.2%; OR 0.19 [95% CI, 0.08-0.48]; NNT 23) but only when 2 trials with high-risk patients were included. The effect of alpha(2)-agonists on myocardial infarction was not significant (6.1% versus 7.3%; OR 0.85 [95% CI, 0.62-1.14]). beta-blockers significantly decreased the risk of cardiac death from 3.9% to 0.8% (OR 0.25 [95% CI, 0.09-0.73], NNT 32). alpha(2)-agonists significantly decreased the risk of cardiac death from 2.3% to 1.1% (OR 0.50 [95% CI, 0.28-0.91], NNT 83). For calcium channel blockers and nitroglycerin, evidence of any benefit was lacking. The most common adverse effect was bradycardia, which occurred in 24.5% of patients receiving a beta adrenergic blocker versus 9.1% of controls (OR 3.76 [95% CI, 2.45-5.77], NNH 6).