Perioperative β-Blockade in Noncardiac Surgery: A Cautionary Tale of Over-reliance on Small Randomized Prospective Trials.

Purpose: Our aim was to analyze the current scientific literature relevant to the use of β-adrenergic receptor antagonists for the prevention of cardiovascular morbidity and mortality in patients undergoing noncardiac surgery.

Methods: A PubMed search was conducted for the following concepts: pre- or perioperative, β-adrenergic receptor antagonist, treatment outcome, and cardiovascular complication. Randomized clinical trials measuring the effect of β-adrenergic blocking agents against that of placebo on cardiovascular outcomes after noncardiac surgery were included in the review.

Findings: Two small randomized controlled trials published in 1996 and 1999 reported associations between perioperative β-blockade and significant reductions in long-term and 30-day cardiac mortality, respectively. These 2 studies prompted guideline changes in 2002 encouraging perioperative β-blockade in subsets of noncardiac surgery patients. However, subsequent trials failed to validate these results. In 2008, the first large randomized controlled trial on the topic was published and found an association between perioperative β-blockade and an increase in perioperative mortality. Furthermore, in 2011, the lead author of the 1999 study was dismissed from his academic position for scientific misconduct, casting doubt on the validity of guidelines based on his work. Existing studies are highly heterogeneous, making comparisons difficult. Current literature does not support initiating perioperative β-blockade in noncardiac surgery patients not already receiving these medications.

Implications: Future research on the topic should account for the influence individual genetic variation can have on outcomes and β-blocker metabolism. Additionally, the relationship between outcomes and the β-1 selectivity of different β-blockers should be explored.