Variations in Pharmacology of β-Blockers May Contribute to Heterogeneous Results in Trials of Perioperative β-Blockade

• Published in: Anesthesiology (Philadelphia) 2010-09, Vol.113 (3), p.585-592
• Main Authors: BADGETT, Robert G, LAWRENCE, Valerie A, COHN, Steven L
• Format: Article
• Language: English
• Subjects: Adrenergic beta-Antagonists - pharmacology; Anesthesia; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Cytochrome P-450 CYP2D6 - genetics; Cytochrome P-450 CYP2D6 - metabolism; Genetic Variation - drug effects; Genetic Variation - genetics; Humans; Medical sciences; Perioperative Care - methods; Polymorphism, Genetic - drug effects; Randomized Controlled Trials as Topic - methods
• ISSN: 0003-3022; 1528-1175
• DOI: 10.1097/ALN.0b013e3181e73eea

Randomized controlled trials and meta-analyses provide conflicting guidance on the role of beta-adrenergic receptor blockers (beta-blockers) in reducing perioperative complications. We hypothesize that variability in trial results may be due in part to heterogeneous properties of beta-blockers. First, we propose that the extent of beta-blocker metabolism by cytochrome P-450 and the time available to titrate the dosage before surgery (titration time) may interact; dependence on P-450 may be most harmful when titration time is short. Second, beta-blockers vary in their selectivity for the beta-1 receptor and reduced selectivity may contribute to cerebral ischemia. We used meta-analysis and meta-regression of existing trials to explore the role of these pharmacological properties. We found that both of these pharmacological factors are significantly associated with reduced efficacy of beta-blockers. Pharmacological properties of beta-blockers may contribute to heterogeneous trial results. Many trials have used metoprolol, which is extensively metabolized by cytochrome P450 and is less selective for the beta-1 receptor. For these two reasons, the efficacy of metoprolol to prevent perioperative cardiac complications should be compared with the efficacy of other beta-blockers.