DB’s Medical Rants

Once again a study challenges dogma - POISE Published, Debate on Perioperative Beta Blockers Continues

Publication of the landmark Perioperative Ischemic Evaluation (POISE) trial online May 12, 2008, in the Lancet has triggered another heated debate about the pros and cons of using beta blockers perioperatively in noncardiac surgery [1]. In one corner are the authors of POISE, which was first reported at the American Heart Association (AHA) 2007 Scientific Session and which found that beta blockers do more harm than good in this setting; and in the other, two accompanying editorialists, who suggest that it is the POISE protocol—specifically, the doses of beta blocker used and timing of initiation of therapy—that explains the findings and that a different protocol might shift the risk/balance back in favor of using beta blockers in this setting [2].

"What POISE says is that in the dosing we used, we see beta blockers have substantial risk in the perioperative setting," Dr Philip J Devereaux (McMaster University, Hamilton, ON) told heartwire. "And until someone demonstrates with a clear and large randomized controlled trial that an alternative dose is both effective and safe, it’s just not rational, not in people’s best interests, to be assuming—that’s how we got into this trouble in the first place."

I have not done preoperative and perioperative management for many years, and have not followed this literature carefully.  I did know that most experts thought that beta blockers markedly decreased MI risk during and after non-cardiac surgery.  So as a more casual observer, this article surprised me.

Devereaux first reported POISE—a randomized controlled trial in more than 8000 patients undergoing noncardiac surgery who were not on beta blockers, randomized to either the beta blocker metoprolol or placebo—at the AHA meeting last year. The results showed that the beta blocker reduced the risk of myocardial infarction (MI) but increased the risk of severe stroke and overall death in patients undergoing noncardiac surgery. It suggested that for every 1000 patients treated, metoprolol would prevent 15 MIs, but there would be an excess of eight deaths and five severe disabling strokes.

Devereaux told heartwire that the new analysis featured in the Lancet "helps to explain why death went up and stroke went up [with metoprolol]. Death was clearly driven by a hypotensive state, leading to shock, which we’ve recognized is so common in the perioperative setting, and that’s what tipped the balance and why we saw the excess death. Also it’s not that simple to predict who will develop shock, and many people who are going to get it are the same people who are going to get a heart attack also."

He and his coinvestigators conclude: "Patients are unlikely to accept the risk associated with perioperative extended-release metoprolol. Current perioperative guidelines that recommend beta-blocker therapy to patients undergoing noncardiac surgery should reconsider their recommendations in light of these findings."

I take several messages from this study.  First, we really do not know answers to complex clinical questions until we careful prospective studies, especially randomized controlled clinical trials.  Second, the performance indicator and safety movement which has a "ready, fire, aim" philosophy, must reevaluate their strategies.  One must wonder if our current push towards performance measurement has caused strokes and death in some patients.  Finally, 30 years after finishing my residency, I continue to reshape my medical knowledge.  As new knowledge appears we must quickly adjust our practice.  I am interested in the ability of the performance movement to adjust.  Of course, they will shrug off the unintended consequences that they caused here.