September 2013
More Perioperative Beta-Blocker Controversy
In our May 2013 What’s New in the Patient Safety World column “Beta Blocker Debate Just Won’t Go Away” we joked that one pro-beta-blocker article always engenders another anti-beta-blocker article and vice versa! You guessed it – here’s more!
Most of you recall the history of the debate. After several years in which we pushed for almost universal use of beta blockers perioperatively, publication of the POISE trial (Devereaux 2008) significantly changed things. 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. Largely since that time recommendations have been to continue beta blockers in the perioperative period in patients previously taking them but most no longer begin them perioperatively in patients not previously taking them.
But there have been numerous criticisms of the POISE trial. Specifically, patients received fairly large doses of metoprolol shortly before their surgery and many have argued that starting beta blockers well in advance of surgery and titrating the dose slowly would not have produced the adverse outcomes seen in POISE.
In the interim, serious questions about the conduct and validity of several prior studies supporting the use of perioperative beta blockers have been raised (see the new study by Bouri et al. discussed below).
A number of retrospective observational studies had suggested that there might be a benefit from perioperative beta blockers in some cases. The most recent observational study again that we discussed in our May 2013 What’s New in the Patient Safety World column “Beta Blocker Debate Just Won’t Go Away” raised the question of utility of perioperative beta blockers in patients undergoing noncardiac surgery. That study (London 2013) found that among propensity-matched control patients undergoing noncardiac, nonvascular surgery, perioperative β-blocker exposure was associated with lower rates of 30-day all-cause mortality in patients with 2 or more Revised Cardiac Risk Index factors. But even that study has been questioned regarding potential bias due to the methodology used (see Mansi 2013 and the reply by London 2013b).
Because of the issues surrounding the series of pro-beta-blocker studies, a new meta-analysis of beta-blockade in non-cardiac surgery was undertaken excluding the discredited studies (Bouri 2013). The conclusion of that meta-analysis was that beta-blockade caused a 27% increase in all-cause mortality. While the rate of non-fatal MI was significantly reduced in that meta-analysis the rates of stroke and hypotension were increased in addition to the increased mortality rates. Note that the meta-analysis was dominated by the large POISE trial already mentioned above. Note also that the authors rebut some of the criticisms of the POISE trial related to dose and titration. The authors call for various specialty societies to revise their guidelines regarding beta-blockade in non-cardiac surgery until further randomized controlled trials are done.
We concur that the controversy is unlikely to go away until a large randomized controlled trial is undertaken using a beta-blockade regimen that everyone can agree upon.
Our prior columns on perioperative use of beta blockers:
November 20, 2007 “New Evidence Questions Perioperative Beta Blocker Use”
November 4, 2008 “Beta Blockers Take More Hits”
December 2009 “Updated Perioperative Beta Blocker Guidelines”
November 2010 “More Perioperative Beta Blocker Controversy”
November 2012 “Beta
Blockers Losing Their Luster?”
May 2013 “Beta
Blocker Debate Just Won’t Go Away”
References:
Devereaux PJ, Yang H, Yusuf S, et al for the POISE Study Group. Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled trial. Lancet 2008; 371(9627): 1839-1847
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2808%2960601-7/fulltext
London MJ, Hur K, Schwartz GG, Henderson WG. Association of Perioperative β-Blockade With Mortality and Cardiovascular Morbidity Following Major Noncardiac Surgery. JAMA 2013; 309(16): 1704-1713
http://jama.jamanetwork.com/article.aspx?articleid=1681412
Mansi I, Mortensen EM. Mortality After Perioperative β-Blocker Use in Noncardiac Surgery. JAMA 2013; 310(6): 645-646
http://jama.jamanetwork.com/article.aspx?articleid=1728707
London MJ, Schwartz GG, Henderson WG. Mortality After Perioperative β-Blocker Use in Noncardiac Surgery—Reply. JAMA 2013; 310(6): 646
http://jama.jamanetwork.com/article.aspx?articleid=1728709
Bouri S, Shun-Shin MJ, Cole GD, Mayet J, Francis DP. Meta-analysis of secure randomised controlled trials of β-blockade to prevent perioperative death in non-cardiac surgery. Heart 2013; Published Online First: 31 July 2013 doi:10.1136/heartjnl-2013-304262
http://heart.bmj.com/content/early/2013/07/30/heartjnl-2013-304262.full.pdf+html
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