Sunday, July 29, 2007

Perioperative beta blockers: not so fast!

The initial enthusiasm for perioperative beta blockers was soon tempered by conflicting studies. In an effort to address the controversy the American College of Cardiology (ACC) issued guidelines last year which were somewhat more conservative than previous recommendations. Their class I recommendation was restricted to those patients who were already taking beta blockers and patients undergoing vascular surgery who had had ischemia demonstrated on preoperative testing. A class IIa recommendation was given for all other patients undergoing vascular surgery in addition to certain other high risk patients.

But now we must ask whether the guidelines are evidence based. The MaVS trial, the largest blinded RCT published at that time, demonstrated no benefit from perioperative metoprolol. The study, published last fall in the American Heart Journal, was composed of patients undergoing vascular surgery, a group that would be expected to uniquely benefit from beta blockers.

According to an editorial in the same issue “Larger and even more convincing trials are in the process of publication, demonstrating no impact of beta-blockade on perioperative events.” One of these, the DIPOM trial, was presented at the 2004 American Heart Association scientific sessions.

The editorial writer believes that poor quality studies combined with initial “belief” in the protective effects of beta blockers led to premature endorsement. An appeal to pathophysiology might help explain a lack of observed effect. Most ischemic cardiac events, particularly in this era of revascularization, are caused by rupture of a vulnerable (and often non hemodynamically significant) plaque, a process not mitigated by beta blockers. The relatively few patients with severe epicardial coronary disease who are susceptible to acute increases in myocardial oxygen demand might benefit.

As discussed in the editorial, these pathophysiologic considerations have fuelled interest in the use of statin drugs for perioperative cardiac protection. Early evidence suggests a strong protective effect. At least one larger trial is in progress. While it may be too early to recommend routine perioperative use of statins it is probably safe to say that patients with coronary disease already taking statins should continue them through the perioperative period.

Are perioperative beta blockers evidence based? It would seem that the answer is a cautious no. Should the ACC guideline be followed? There is strong pathophysiologic rationale for the class I indication. Patients already taking beta blockers should probably have them continued as seamlessly as possible perioperatively. The hemodynamic stress of surgery combined with the hemodynamic stress of beta blocker withdrawal might put patients at risk for ischemic events. Those undergoing vascular surgery who demonstrated ischemia on preoperative stress testing are more likely to have severe epicardial coronary artery disease and be susceptible to hemodynamic stress which would be mitigated by beta blockers.

The editorial’s pessimistic view of perioperative beta blockers is summarized by--

Where did the evidence-based guidelines process go wrong? The most readily apparent answer is in the reliance of small and in some cases unblinded trials, which had sparse absolute differences in event rates. When this is encountered in a systematic review, it should be realized that by random error, if a handful of events occurred in the opposite group by chance alone, then the significant result could not have been found. Thus, based on an intuitive and expected effect with beta-blockers, the ACC/AHA guidelines process has produced recommendations that almost certainly will be reversed.

For now, pending further results from clinical trials, I intend to follow the ACC guidelines for the class I indication, consider statin use in high risk patients, and continue statins perioperatively, when possible, in those patients already on statins. I also look for statins to emerge as the “next beta blockers” for perioperative treatment in the coming years.

1 comment:

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