LETTER TO THE EDITOR
Beta-Blockade and Noncardiac Surgery To the Editor: We were interested to read Guay & Ochroch’s meta-analysis of the influence of beta-blocking drugs on mortality and major outcomes at the time of surgery.1 Unfortunately, the conclusions of the meta-analysis cannot be relied on for a number of reasons. It is now accepted that the Mangano et al study was flawed for several distinct reasons.2 First, patients recruited for the trial were allocated to treatment or placebo irrespective of their prior treatment with beta-blockers. Consequently, the placebo group contained a higher percentage of patients who recently had ceased beta-blockers and were, therefore, at higher risk of myocardial infarction than the treatment group.3 Second, more patients in the treatment group suffered adverse cardiac events than in the placebo group; some of these adverse cardiac events occurred in the hospital. However, the analysis of the 2-year mortality excluded the in-hospital adverse events and analyzed only the adverse events after hospital discharge.2 This unusual treatment of the patients led Devereaux and colleagues to exclude the study from his meta-analysis of beta-blocker treatment at the time of surgery because the analysis was not on the basis of “intention to treat” and, therefore, did not meet sound statistical principles.4 We commented on this unusual analysis in our accompanying BMJ editorial.5 We have continued to make the same point from the same standpoint.6,7
The work of Don Polderman et al Dutch cardiovascular research group has recently been called into question and the Erasmus University in Rotterdam has withdrawn scientific approval for all but the first Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography (DECREASE) study.7 Thus, Guay and Ochroch should have excluded the Mangano et al, DECREASE IV, and DECREASE VI studies from their meta-analysis.2,8,9 We suspect that if such precautions had been taken the metaanalysis would have concluded that there was no benefit from routine perioperative beta-blockade at the time of noncardiac surgery.5–7 The question of the harm that can accrue from the initiation of such therapy at the time of noncardiac surgery, in the mistaken belief that it will improve outcomes, is still being debated.7,10 However, the excess mortality of 27% in betablocker–treated patients is important and has been estimated to be as many as 10,000 deaths in the UK annually.7,10 This may prompt the authors, or the Journal, to withdraw the article or the conclusion that “β-blockers reduced the 1-year risk of death postsurgery.” We hope that they will. Stephen N. Bolsin, BSc, MBBS, FRCA, FANZCA MHSM, DLit (Hon)* Mark Colson, MBBS, FANZCA† Angela Marsiglio, MBBS‡ *The Geelong Hospital, Melbourne, Australia †Geelong, Victoria, Australia ‡Mercy Hospital, Melbourne, Victoria, Australia
REFERENCES 1. Guay J, Ochroch EA: Beta-blocking agents for surgery: Influence on mortality and major outcomes. A meta-analysis. J Cardiothorac Vasc Anesth 27(5):834-844, 2013 2. Mangano DT, Layug E, Wallace A, et al: Effect of atenolol on mortality and cardiovascular morbidity after noncardiac surgery. N Engl J Med 335(23):1713-1721, 1996 3. Petros JA: Effect of atenolol on mortality and cardiovascular morbidity after noncardiac surgery. N Engl J Med 336:1452, 1997 4. Devereaux PJ, Beattie WS, Choi P, et al: How strong is the evidence for the use of perioperative β blockers in non-cardiac surgery? Systematic review and meta-analysis of randomised controlled trials. BMJ 331(6 Aug):313-321, 2005 5. Bolsin S, Colson M: Beta-blockers for patients at risk of cardiac events during non-cardiac surgery. BMJ 331(7522): 919-920, 2005 6. Bolsin S, Colson M, Conroy M: ß-blockers and statins in noncardiac surgery. BMJ 334(7607):1283-1284, 2007
7. Bolsin SN, Colson M, Marsiglio A: Perioperative beta-blockade. BMJ 347:9, 2013 8. Dunkelgrun M, Boersma E, Schouten O, et al: Bisoprolol and fluvastatin for the reduction of perioperative cardiac mortality and myocardial infarction in intermediate-risk patients undergoing noncardiovascular surgery: A randomized controlled trial (DECREASE-IV). Ann Surg 249(6):921-926, doi:http://dx.doi.org/10.1097/SLA.0b013e 3181a77d00, 2009 9. Poldermans D, Boersma E, Bax JJ, et al: The effect of bisoprolol on perioperative mortality and myocardial infarction in high-risk patients undergoing vascular surgery. N Engl J Med 341(24):1789-1794, 1999 10. Bouri S, Shun-Shin MJ, Cole GD, et al: Meta-analysis of secure randomised controlled trials of β-blockade to prevent perioperative death in non-cardiac surgery. Heart http://dx.doi.org/10.1136/heartjnl2013-304262, Jul 31, 2013
Journal of Cardiothoracic and Vascular Anesthesia, Vol ], No ] (Month), 2014: pp ]]]–]]]
http://dx.doi.org/10.1053/j.jvca.2014.01.013
1
Beta-Blockade and Noncardiac Surgery To the Editor: We were interested to read Guay & Ochroch’s meta-analysis of the influence of beta-blocking drugs on mortality and major outcomes at the time of surgery.1 Unfortunately, the conclusions of the meta-analysis cannot be relied on for a number of reasons. It is now accepted that the Mangano et al study was flawed for several distinct reasons.2 First, patients recruited for the trial were allocated to treatment or placebo irrespective of their prior treatment with beta-blockers. Consequently, the placebo group contained a higher percentage of patients who recently had ceased beta-blockers and were, therefore, at higher risk of myocardial infarction than the treatment group.3 Second, more patients in the treatment group suffered adverse cardiac events than in the placebo group; some of these adverse cardiac events occurred in the hospital. However, the analysis of the 2-year mortality excluded the in-hospital adverse events and analyzed only the adverse events after hospital discharge.2 This unusual treatment of the patients led Devereaux and colleagues to exclude the study from his meta-analysis of beta-blocker treatment at the time of surgery because the analysis was not on the basis of “intention to treat” and, therefore, did not meet sound statistical principles.4 We commented on this unusual analysis in our accompanying BMJ editorial.5 We have continued to make the same point from the same standpoint.6,7
The work of Don Polderman et al Dutch cardiovascular research group has recently been called into question and the Erasmus University in Rotterdam has withdrawn scientific approval for all but the first Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography (DECREASE) study.7 Thus, Guay and Ochroch should have excluded the Mangano et al, DECREASE IV, and DECREASE VI studies from their meta-analysis.2,8,9 We suspect that if such precautions had been taken the metaanalysis would have concluded that there was no benefit from routine perioperative beta-blockade at the time of noncardiac surgery.5–7 The question of the harm that can accrue from the initiation of such therapy at the time of noncardiac surgery, in the mistaken belief that it will improve outcomes, is still being debated.7,10 However, the excess mortality of 27% in betablocker–treated patients is important and has been estimated to be as many as 10,000 deaths in the UK annually.7,10 This may prompt the authors, or the Journal, to withdraw the article or the conclusion that “β-blockers reduced the 1-year risk of death postsurgery.” We hope that they will. Stephen N. Bolsin, BSc, MBBS, FRCA, FANZCA MHSM, DLit (Hon)* Mark Colson, MBBS, FANZCA† Angela Marsiglio, MBBS‡ *The Geelong Hospital, Melbourne, Australia †Geelong, Victoria, Australia ‡Mercy Hospital, Melbourne, Victoria, Australia
REFERENCES 1. Guay J, Ochroch EA: Beta-blocking agents for surgery: Influence on mortality and major outcomes. A meta-analysis. J Cardiothorac Vasc Anesth 27(5):834-844, 2013 2. Mangano DT, Layug E, Wallace A, et al: Effect of atenolol on mortality and cardiovascular morbidity after noncardiac surgery. N Engl J Med 335(23):1713-1721, 1996 3. Petros JA: Effect of atenolol on mortality and cardiovascular morbidity after noncardiac surgery. N Engl J Med 336:1452, 1997 4. Devereaux PJ, Beattie WS, Choi P, et al: How strong is the evidence for the use of perioperative β blockers in non-cardiac surgery? Systematic review and meta-analysis of randomised controlled trials. BMJ 331(6 Aug):313-321, 2005 5. Bolsin S, Colson M: Beta-blockers for patients at risk of cardiac events during non-cardiac surgery. BMJ 331(7522): 919-920, 2005 6. Bolsin S, Colson M, Conroy M: ß-blockers and statins in noncardiac surgery. BMJ 334(7607):1283-1284, 2007
7. Bolsin SN, Colson M, Marsiglio A: Perioperative beta-blockade. BMJ 347:9, 2013 8. Dunkelgrun M, Boersma E, Schouten O, et al: Bisoprolol and fluvastatin for the reduction of perioperative cardiac mortality and myocardial infarction in intermediate-risk patients undergoing noncardiovascular surgery: A randomized controlled trial (DECREASE-IV). Ann Surg 249(6):921-926, doi:http://dx.doi.org/10.1097/SLA.0b013e 3181a77d00, 2009 9. Poldermans D, Boersma E, Bax JJ, et al: The effect of bisoprolol on perioperative mortality and myocardial infarction in high-risk patients undergoing vascular surgery. N Engl J Med 341(24):1789-1794, 1999 10. Bouri S, Shun-Shin MJ, Cole GD, et al: Meta-analysis of secure randomised controlled trials of β-blockade to prevent perioperative death in non-cardiac surgery. Heart http://dx.doi.org/10.1136/heartjnl2013-304262, Jul 31, 2013
Journal of Cardiothoracic and Vascular Anesthesia, Vol ], No ] (Month), 2014: pp ]]]–]]]
http://dx.doi.org/10.1053/j.jvca.2014.01.013
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