The now published results of the POISE trial raises the question that the rush to make peri-operative beta blockers a quasi-mandatory quality measure may have lead to a number of deaths from stroke . Could that possibly be right?
In the words of at least one of the trial investigators the answer is yes.Dr. P.J. Devereaux's comments can be found here in Medscape news report describing the trial and various commentators' reactions to the results.
POISE was a large ( 8000 plus subjects) randomized trial designed to determine the effect of the peri-operative use of Metoprolol-XL. 100 mg was given 2-4 hours preop and again 0-6 hours post op and then 200mg daily for thirty days.
Total mortality was increased in the treatment arm (3.1% versus 2.3%,Hazard ratio 1.33,p=03) while myocardial infarctions were decreased but strokes were increased.Strokes occurred in 1% of the treatment arm patients versus 0.5 5,Hazard ratio 2.17. Hypotension was also significantly increased in the treatment arm while the incidence of atrial fibrillation was decreased.
Critics of the trial might argue that the dose of Metoprolol was simply too high and too much of this putative good thing might well cause more hypotension. They might argue that POISE only demonstrated that if you give an inappropriate dose of a beta blocker you cause harm. But I do not believe that the results of the trial will be dismissed based on different experts differing on dosing details of the trial.More likely major changes in guidelines will be made.(I will have to admit that if I took 200 mg of metoprolol a day, I would move like a turtle and have a heart of 12.)
If there is a lesson here it is not just that a large randomized clinical trial gives results opposite to earlier smaller trials-that is a story we have heard more than once before. The lesson is not that expert committees sometimes have to revise their recommendations as new information becomes available.The lesson I think that should be emphasized is that overzealous quality rule writers and enforcers can be a hazard to your health ( and I have said that before). Read Dr. Devereaux's comments regarding how many patients may have been harmed by taking peri operative beta blockers and then wonder how many patients received them simply because premature quality guidelines were in place and physicians were caught up in the rush to treat even though it seems clear now that the evidence for such zealous efforts was inadequate.
Dr. DB (AKA Dr. Robert Centor) nailed it when he recently spoke about in this regard " the performance and quality movement which has a 'ready,fire, aim' philosophy".