Beta-blockers for cardiac risk reduction in people undergoing non-cardiac vascular surgery

Background

As the population is ageing, more people will undergo major vascular surgery, which carries an increased risk of cardiac complications. The increased risk of cardiac complications is often the result of asymptomatic heart disease. Treating severe symptoms, such as critical limb ischaemia (severely narrowed arteries of the lower limbs resulting in rest pain, ulcers, or gangrene), in people with peripheral arterial disease is a common reason for undergoing vascular surgery, which carries an increased risk heart attack (myocardial infarction) ranging from 5% to 24% during and shortly after surgery. There is clear evidence for the use of beta-blockers (a class of medications used to treat certain heart conditions as well as high-blood pressure and other conditions) to reduce cardiac risk in people with known heart disease, and it has been suggested that beta-blockers may reduce short-term cardiac illness (morbidity) and death (mortality) in people undergoing major non-cardiac vascular surgery.

Study characteristics

We identified two studies that evaluated beta-blockers giving during surgery (perioperatively) in people undergoing major non-cardiac vascular surgery, with follow-up data on cardiovascular outcomes. A total of 599 participants were randomised to receive beta-blockers (301 participants) or placebo (298 participants). Both studies were double-blind (neither participants nor surgeon were aware of the treatment), randomised controlled trials evaluating the beta-blocker, metoprolol.

Key results

The results of the analysis offered no clear evidence that perioperative beta-blockers reduced death from any cause (all-cause mortality), cardiovascular death, non-fatal heart attack, irregular heartbeat (arrhythmia), heart failure, stroke, combined cardiovascular events or re-hospitalisation at 30 days. There was evidence to support that beta-blockers increased the risk of intra-operative low heart rate (bradycardia) and low blood pressure (hypotension). These complications should be weighed with any benefit when considering the use of beta-blockers in this population.

Quality of the evidence

Study quality was good for both trials. One trial did not adequately describe their randomisation techniques and the other trial did not report whether the outcome assessors were blinded to the treatment group, and was possibly underpowered. With only two studies included, several of the outcomes only had data from a single study, and neither of the studies reported on blockage or obstruction of blood vessels (vascular patency/graft occlusion), reducing the quality of evidence to moderate.

Authors' conclusions: 

This meta-analysis currently offers no clear evidence that perioperative beta-adrenergic blockade reduces postoperative cardiac morbidity and mortality in people undergoing major non-cardiac vascular surgery. There is evidence that intra-operative bradycardia and hypotension are more likely in people taking perioperative beta-adrenergic blockers, which should be weighed with any benefit.

Read the full abstract...
Background: 

People undergoing major vascular surgery have an increased risk of postoperative cardiac complications. Beta-adrenergic blockers represent an important and established pharmacological intervention in the prevention of cardiac complications in people with coronary artery disease. It has been proposed that this class of drugs may reduce the risk of perioperative cardiac complications in people undergoing major non-cardiac vascular surgery.

Objectives: 

To review the efficacy and safety of perioperative beta-adrenergic blockade in reducing cardiac or all-cause mortality, myocardial infarction, and other cardiovascular safety outcomes in people undergoing major non-cardiac vascular surgery.

Search strategy: 

The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (January 2014) and the Cochrane Central Register of Controlled Trials (CENTRAL; 2013, Issue 12). We searched trials databases and checked reference lists of relevant articles.

Selection criteria: 

We included prospective, randomised controlled trials of perioperative beta-adrenergic blockade of people over 18 years of age undergoing non-cardiac vascular surgery.

Data collection and analysis: 

Two review authors independently performed study selection and data extraction. We resolved disagreements through discussion. We performed meta-analysis using a fixed-effect model with odds ratios (ORs) and 95% confidence intervals (CIs).

Main results: 

We included two studies in this review, both of which were double-blind, randomised controlled trials comparing perioperative beta-adrenergic blockade (metoprolol) with placebo, on cardiovascular outcomes in people undergoing major non-cardiac vascular surgery. We included 599 participants receiving beta-adrenergic blockers (301 participants) or placebo (298 participants). The overall quality of studies was good. However, one study did not report random sequence generation or allocation concealment techniques, indicating possible selection bias, and the other study did not report outcome assessor blinding and was possibly underpowered. It should be noted that several of the outcomes were only reported in a single study and neither of the studies reported on vascular patency/graft occlusion, which reduces the quality of evidence to moderate. There was no evidence that perioperative beta-adrenergic blockade reduced all-cause mortality (OR 0.62, 95% CI 0.03 to 15.02), cardiovascular mortality (OR 0.34, 95% CI 0.01 to 8.32), non-fatal myocardial infarction (OR 0.83, 95% CI 0.46 to 1.49; P value = 0.53), arrhythmia (OR 0.70, 95% CI 0.26 to 1.88), heart failure (OR 1.71, 95% CI 0.40 to 7.23), stroke (OR 2.67, 95% CI 0.11 to 67.08), composite cardiovascular events (OR 0.87, 95% CI 0.55 to 1.39; P value = 0.57) or re-hospitalisation at 30 days (OR 0.86, 95% CI 0.48 to 1.52). However, there was strong evidence that beta-adrenergic blockers increased the odds of intra-operative bradycardia (OR 4.97, 95% CI 3.22 to 7.65; P value < 0.00001) and intra-operative hypotension (OR 1.84, 95% CI 1.31 to 2.59; P value = 0.0005).

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