PERIOPERATIVE CARDIOVASCULAR MEDICAL OPTIMIZATION AND 30-DAY MAJOR ADVERSE CARDIAC EVENTS IN ADULTS UNDERGOING MAJOR NON-CARDIAC SURGERY: A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract

Background:

Major adverse cardiac events are a significant cause of early morbidity and death following major non-cardiac surgery. Postoperative myocardial infarction and cardiac death are widespread even in the context of modern perioperative risk stratification and monitoring, especially in individuals with a history of cardiovascular disease. Various pharmacologic strategies, including beta-blockers, antiplatelet agents, alpha-2 agonists and statins have been studied to decrease the risk of perioperative cardiac events; however, there have been inconsistent results with randomized trials. A comprehensive synthesis of randomized evidence is needed to clarify the overall effectiveness of perioperative cardiovascular medical optimization on reduction of short-term major adverse cardiac events.

Objectives:

To assess the impact of perioperative cardiovascular medical optimization on 30-day death or non-fatal myocardial infarction in adults undergoing major non-cardiac surgery, and to examine effects of treatment by class of medication used.

Methods:

A systematic review and meta-analysis of randomized controlled trials was performed. Eight independent RCT comparisons were included: four trials of beta-blockers (POISE I, DIPOM, POBBLE and Mangano); one trial of antiplatelet agents (POISE II aspirin); two trials of alpha-2 agonists (POISE II clonidine and EPIC); one trial of statins (Durazzo). The first endpoint was 30-day death or non-fatal myocardial infarction. Pooled risk ratios (RR) were estimated using a random effect model (DerSimonian-Laird) and statistical heterogeneity was evaluated by the I² statistic.

Results:

A total of 15,875 patients were included in eight randomized comparisons. Overall, perioperative cardiovascular pharmacologic optimization did not have a significant effect on the composite outcome of 30-day death or non-fatal myocardial infarction compared with control (RR 0.96, 95% CI 0.80–1.15; I² = 58%). Subgroup analysis showed that there was not any statistically significant association between beta-blockers and the primary outcome (RR 0.88, 95% CI 0.64 - 1.21; I² = 35%). Aspirin treatment was not found to be significant (RR 0.99, 95% CI 0.86-1.14). Alpha-2 agonists were not linked with better outcomes (RR 1.15, 95% CI 0.83-1.59; I²=20%). In contrast, perioperative statin therapy had a significant reduction in the composite endpoint (RR 0.23, 95% CI 0.07-0.76), although this was based on one small randomized trial. Moderate heterogeneity existed in the overall model that appeared to be accounted for by differences in class of pharmacologic and baseline surgical risk.

Conclusion:

Perioperative cardiovascular pharmacologic optimization was not associated with significant reduction of 30-day death or non-fatal myocardial infarction overall. While beta-blockers, aspirin and alpha-2 agonists showed no consistent protective effect, there was some potential benefit from statin therapy in high-risk vascular surgery populations. These findings endorse specific perioperative cardiovascular risk assessment and specific pharmacologic strategies consistent with guidelines from the past couple of years.