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

Abstract

In Brief 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 β-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. β-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). α2-agonists decreased ischemia during surgery only (19.4% versus 32.8%; OR 0.47 [95% CI, 0.33–0.68]; NNT 7). β-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 α2-agonists on myocardial infarction was not significant (6.1% versus 7.3%; OR 0.85 [95% CI, 0.62–1.14]). β-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). α2-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 β adrenergic blocker versus 9.1% of controls (OR 3.76 [95% CI, 2.45–5.77], NNH 6). IMPLICATIONS: Among the drugs that have been tested in randomized-controlled trials, β-blockers, clonidine, and mivazerol are effective in preventing cardiac complications in patients undergoing noncardiac surgery. For β-blockers, high-risk patients are most likely to benefit from treatment. Valid studies are required to directly compare the efficacy of these classes of drug and determine how dose, timing, and duration of treatment influence outcome.