Many of you have been following the interesting series of articles explaining why some things in medicine sound too good to be true and eventually turn out not to be true or at least not as good as initially thought Lehrer 2007). Most such studies initially had relatively small numbers and were subject to a number of biases. With time and further attempts at replication the results become much less impressive.
Use of beta blockers probably exemplifies that concept as well as anything else in medicine. Back in the 1980’s a number of randomized controlled trials showed that patients suffering acute myocardial infarction (AMI) had a substantial reduction in mortality if they were treated with beta blockers. The mean duration of followup in those studies was a little more than a year. From those studies we extrapolated and began to recommend such patients be continued on beta blockers ad infinitum. Moreover, we also extrapolated the need for beta blockers to patients with coronary artery disease (CAD) but no known MI and even to patients just having multiple risk factors for coronary artery disease.
Now researchers using the REACH registry (patients with or at high risk of coronary artery disease followed longitudinally for several years) have looked retrospectively at outcomes of patients in some of the above categories to determine whether beta blockers had an impact (Bangalore 2012). In fact, there was no significant difference in outcomes in the MI cohort for those taking beta blockers and those not taking them. In the CAD without MI cohort there also was no difference. And in the cohort just having risk factors for CAD there was actually a higher rate of adverse events in those patients taking beta blockers. Admittedly this is just an observational study and there are many unanswered questions but these results certainly challenge some longstanding practices. The results support the most recent AHA recommendations for use of beta blockers in patients with acute MI, acute coronary syndrome, and congestive heart failure. But they certainly suggest that many other patients may be inappropriately taking beta blockers.
The other controversial area, one which we have addressed on many occasions, is perioperative use of beta blockers. The controversy over perioperative use of beta blockers just won’t go away. We’ve addressed the issue in multiple columns (see Patient Safety Tips of the Week for November 20, 2007 “New Evidence Questions Perioperative Beta Blocker Use” and November 4, 2008 “Beta Blockers Take More Hits”, our December 2009 What’s New in the Patient Safety World column “Updated Perioperative Beta Blocker Guidelines” and our November 2010 What’s New in the Patient Safety World column “More Perioperative Beta Blocker Controversy”).
After several years in which we pushed for almost universal use of beta blockers perioperatively, publication of the POISE trial significantly changed things. You’ll recall that the POISE trial showed that, though preoperative beta blockers prevented 15 MI’s for every 1000 patients treated, there was an increased risk of stroke and an excess of 8 deaths per 1000 patients treated.
Recent revelations regarding potential irregularities in the published works of one of the most prolific researchers in the perioperative beta blocker field have further challenged the perioperative beta blocker picture (Chopra 2012).
But there are some studies that demonstrate a continued need to continue beta blockers in patients previously taking them. Our November 2010 What’s New in the Patient Safety World column “More Perioperative Beta Blocker Controversy” noted some observational data (Wallace 2010) suggesting that perioperative beta blockade reduces mortality at both 30 days and one year. And that data reinforces that perioperative withdrawal of beta blockers increases mortality. In fact, the Wallace paper showed that beta blocker withdrawal almost quadrupled the 30-day mortality rate and almost doubled the 1-year mortality rate.
Another recent observational study supports the current practice of continuing beta blockers perioperatively in patients who had been taking them prior to their surgery (Kwon 2012). This study, part of a collaborative quality improvement project in Washington state, found that failure to continue beta blockers in patients previously on them almost doubled their rate of adverse events within 90 days after noncardiac surgery.
And, to complicate matters even more, another recent study suggests that mortality is reduced in ICU patients with sepsis who had previously been on beta blockers (Macchia 2012).
We often joke that one pro-beta-blocker article always engenders another anti-beta-blocker article and vice versa! This year has been no different. Lots of still unanswered questions but these serve as a reminder that sometimes evidence-based medicine turns out to be not so evidence-based.
Lehrer J. The Truth Wears Off. The New Yorker. December 13, 2007
Bangalore S, Steg G, Deedwania P, et al. β-Blocker Use and Clinical Outcomes in Stable Outpatients With and Without Coronary Artery Disease. JAMA 2012; 308(13): 1340-1349
Chopra V, Eagle KA. Perioperative Mischief: The Price of Academic Misconduct. Amer J Med 2012; 125(10): 953-955
Wallace AW, Au S, Cason BA. Association of the Pattern of Use of Perioperative ß-Blockade and Postoperative Mortality. Anesthesiology 2010; 113(4): 794-805
Kwon S, Thompson R, Florencem M, et al. β-Blocker Continuation After Noncardiac SurgeryA Report From the Surgical Care and Outcomes Assessment Program
Arch Surg. 2012; 147(5): 467-473
Macchia A, Romero M, Comignani PD, et al. Previous prescription of β-blockers is associated with reduced mortality among patients hospitalized in intensive care units for sepsis. Critical Care Medicine 2012; 40(10): 2768-2772, October 2012.
Print “PDF version”