doi: 10.1161/CIRCOUTCOMES.108.795377
Cardiovascular Perspectives |
Changing the Practice of Perioperative Cardioprotection
Perioperative β-Blockers After POISE (PeriOperative ISchemic Evaluation)
From the Division of Hospital Medicine, University of California San Francisco.
Correspondence to Andrew D. Auerbach MD, MPH, UCSF Department of Medicine Hospitalist Group, 505 Parnassus Ave, Box 0131, San Francisco, CA 94143-0131. E-mail ada{at}medicine.ucsf.edu
Key Words: coronary disease • morbidity • mortality • prevention • surgery
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Introduction |
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 Top Introduction Come in, the Water's...Maybe We Should Tread...Everybody out of the...Life After POISEReferences |
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For the past decade or more, use of perioperative β-blockers was considered a safe and effective approach to reducing the risk of cardiac complications of surgery in a broad spectrum of patients undergoing noncardiac surgery. This initial sentiment was supported by a fairly small number of randomized trials studying a fairly small number of patients. In the past 5 years, however, evidence has been accumulating to suggest that β-blockers were, at the least, ineffective at reducing cardiac events, with the recent PeriOperative ISchemic Evaluation (POISE) study suggesting that the use of perioperative β-blockers produced net harm in surgical patients.
The publication of POISE, therefore, should prompt a fairly substantial change in the approach to using β-blockers in the patient undergoing noncardiac surgery. After POISE, and until more evidence accumulates, the use of β-blockers should be limited primarily to those patients who are on them lifelong or who are on them already. After surgery, the drug should be titrated carefully according to the patient’s clinical situation and continued through discharge.
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Come in, the Water’s Fine: Perioperative β-Blockers 1995 to 2005 |
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TopIntroductionCome in, the Water's...Maybe We Should Tread...Everybody out of the...Life After POISEReferences |
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Between 1996 and 2005, the practice of using β-blockers to prevent postoperative cardiac complications was adopted on the basis of a small number of randomized trials and reviews.1–4 Adoption was speedy because the potential benefit of perioperative β-blockers was large,5 with few attendant risks; rapid adoption was further bolstered because perioperative β-blockers were having the same effects in surgical patients that they had in other patients with coronary artery disease (eg, reducing the risk of death from coronary ischemia).
By 2005, the majority of the evidence supporting perioperative β-blockade was derived from highly screened patient populations undergoing specific procedures (eg, vascular surgery) and receiving agents (eg, intravenous atenolol, oral bisoprolol) not widely available in the United States (Table). The most important limitation of the evidence as of 2005 was that fewer than 1100 patients had been studied in randomized trials; this limitation left these studies open to false-positive results and provided the rationale for the larger randomized studies that followed.6,7
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Maybe We Should Tread Water for a Bit: Perioperative β-Blockers 2005 to 2008 |
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TopIntroductionCome in, the Water's...Maybe We Should Tread...Everybody out of the...Life After POISEReferences |
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Between 2005 and 2007, 3 randomized trials showed no difference between β-blocker–treated and –untreated patients8–10 in terms of risks for major cardiac end points or death. Also in this time period, a meta-analysis of all published studies suggested that the protective effects of β-blockers were less significant than previously thought,11 and a well-designed observational study showed a trend toward higher mortality rate in low-risk patients given β-blockers.12 Partially as a result of these new publications, American College of Cardiology/American Heart Association guidelines updated in 2007 suggested a restrictive approach to administering β-blockers—essentially limiting their use to patients on β-blockers already and to patients with known coronary ischemia who were undergoing vascular surgery.13
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Everybody out of the Pool: Perioperative β-Blockers After POISE |
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TopIntroductionCome in, the Water's...Maybe We Should Tread...Everybody out of the...Life After POISEReferences |
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Publication of POISE, a multicenter study of adequate size and scope to address limitations of previous studies, changes practice substantially.14 The bottom-line conclusions of POISE are a classic good news/bad news story: lower risks for cardiac events (eg, ischemia, atrial fibrillation, need for coronary interventions) but higher net risk for adverse effects when β-blockers are used—with the higher net risk largely related to stroke and higher mortality rate resulting from noncardiac complications. The biggest "problem" with POISE is the starting dose of β-blocker (metoprolol extended release XL 100 mg BID), which does seem high for β-blocker–naïve patients, but for which there was good rationale.7 Although a lower dose of β-blockers probably would have produced fewer strokes, it probably also would have been less effective in reducing ischemia. In fact, a lower starting dose was used in the 3 studies that saw both no harm and no benefit.8,9,15
In addition, POISE did not include a titration protocol before or after surgery. Most of the strokes in POISE appeared to take place early in hospitalization and were presumably related to early effects of the medication in conjunction with the effects of surgery itself. However, lack of titration may not replicate clinical care, where β-blockers are held in the event of bleeding or sepsis, and this is a valid concern for the excess deaths seen in β-blocked patients who had postoperative events that commonly happen later in hospitalization (such as infections or sepsis).
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Life After POISE |
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TopIntroductionCome in, the Water's...Maybe We Should Tread...Everybody out of the...Life After POISEReferences |
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POISE confirmed the growing suspicion prompted by the drumbeat of negative studies (and studies suggesting harm11,12) that preceded it. Although it is possible that early studies were false-positives, it is possible also that early studies were more flawed than we thought; for example, β-blocker discontinuation in placebo-treated patients may have inflated "baseline" risks.1 Moreoever, POISE’s findings of higher rates of hypotension and stroke are consistent with meta-analytic results.11
The counterpoint to POISE comes from researchers in the Netherlands, where perioperative β-blocker administration appears to be managed in a way that is both effective and safe.15 The researchers appear to achieve this balance because they not only can aggressively screen to find actively ischemic patients but can also follow up patients more closely preoperatively as they titrate the β-blockers to a target heart rate. This approach may be difficult to replicate in the United States, where care is more fragmented; patients are often admitted to hospital on the day of surgery, at which point the need for β-blockers may be first discovered; and inconsistent information systems across inpatient and outpatient care settings impede care management.
As we await evidence from trials currently underway,15 the safest approach is to focus on continuing β-blockers in patients on them already and to only start β-blockers perioperatively in patients who need lifelong β-blocker therapy, such as those with known coronary ischemia who are undergoing vascular surgery.13 This general approach mirrors the approach recommended for preoperative revascularization, which should be pursued only in patients who have a clear need for it outside of the context of a planned surgery.13
If a patient is not on β-blockers before surgery, POISE suggests that starting β-blockers immediately beforehand may be harmful, and other studies suggest that this approach is at best ineffective.8–10 A general recommendation would be to start β-blockers as early before surgery as practicable. As much as a month beforehand may be best.2
After surgery, it is critical that focus shifts to continuing β-blockers16,17 appropriately, a process that requires watching β-blocked patients carefully after surgery to assess not only for cardiac events but also for infection, pain, hypovolemia, or bleeding. The careful clinician should use his or her best judgment in titrating or discontinuing β-blockers as situations dictate, ensuring that, if discontinued, β-blockers are restarted as soon as unstable issues are resolved and ensuring that β-blockers are a part of the discharge medication list. A focus on maintaining medication continuity may be useful in the management of patients on statins18,19 as well.
POISE cannot and will not be the last word in the evolution of evidence surrounding use of perioperative β-blockers. Future trials should seek to address the questions reopened by POISE: How long before surgery should the drug be started? How high a dose should be started, and how should it be titrated during the hospital period? How long afterward should it be continued, if not lifelong? Which risk group is most likely to have more benefits than risks from perioperative β-blockers? How should use of β-blockers be combined with use of statins or revascularization20? And perhaps most importantly, how can this knowledge—such as care practices surrounding the use of perioperative β-blockers that appear to be so effective in the Netherlands—be adopted effectively in the United States? POISE clearly should change clinical practice and catalyze research that answers these critical questions.
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Acknowledgments |
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Disclosures
Dr Auerbach has a National Heart, Lung, and Blood Institute–funded research study that is looking at ways to effectively use β-blockers perioperatively.
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Footnotes |
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The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.
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References |
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TopIntroductionCome in, the Water's...Maybe We Should Tread...Everybody out of the...Life After POISEReferences |
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1. Mangano DT, Layug EL, Wallace A, Tateo I. Effect of atenolol on mortality and cardiovascular morbidity after noncardiac surgery. Multicenter Study of Perioperative Ischemia Research Group. N Engl J Med. 1996; 335: 1713–1720.
2. Poldermans D, Boersma E, Bax JJ, Thomson IR, van de Ven LL, Blankensteijn JD, Baars HF, Yo TI, Trocino G, Vigna C, Roelandt JR, van Urk H. The effect of bisoprolol on perioperative mortality and myocardial infarction in high-risk patients undergoing vascular surgery. Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography Study Group. N Engl J Med. 1999; 341: 1789–1794.
3. Boersma E, Poldermans D, Bax JJ, Steyerberg EW, Thomson IR, Banga JD, van De Ven LL, van Urk H, Roelandt JR. Predictors of cardiac events after major vascular surgery: role of clinical characteristics, dobutamine echocardiography, and beta-blocker therapy. JAMA. 2001; 285: 1865–1873.
4. Auerbach AD, Goldman L. β-Blockers and reduction of cardiac events in noncardiac surgery: scientific review. JAMA. 2002; 287: 1435–1444.
5. Lindenauer PK, Fitzgerald J, Hoople N, Benjamin EM. The potential preventability of postoperative myocardial infarction: underuse of perioperative beta-adrenergic blockade. Arch Intern Med. 2004; 164: 762–766.
6. Auerbach A, Goldman L. Assessing and reducing the cardiac risk of noncardiac surgery. Circulation. 2006; 113: 1361–1376.
7. Devereaux PJ, Yang H, Guyatt GH, Leslie K, Villar JC, Monteri VM, Choi P, Giles JW, Yusuf S. Rationale, design, and organization of the PeriOperative ISchemic Evaluation (POISE) trial: a randomized controlled trial of metoprolol versus placebo in patients undergoing noncardiac surgery. Am Heart J. 2006; 152: 223–230.[CrossRef][Medline]
8. Brady AR, Gibbs JS, Greenhalgh RM, Powell JT, Sydes MR. Perioperative beta-blockade (POBBLE) for patients undergoing infrarenal vascular surgery: results of a randomized double-blind controlled trial. J Vasc Surg. 2005; 41: 602–609.[CrossRef][Medline]
9. Yang H, Raymer K, Butler R, Parlow J, Roberts R. The effects of perioperative beta-blockade: results of the Metoprolol after Vascular Surgery (MaVS) study, a randomized controlled trial. Am Heart J. 2006; 152: 983–990.[CrossRef][Medline]
10. Juul AB, Wetterslev J, Gluud C, Kofoed-Enevoldsen A, Jensen G, Callesen T, Norgaard P, Fruergaard K, Bestle M, Vedelsdal R, Miran A, Jacobsen J, Roed J, Mortensen MB, Jorgensen L, Jorgensen J, Rovsing ML, Petersen PL, Pott F, Haas M, Albret R, Nielsen LL, Johansson G, Stjernholm P, Molgaard Y, Foss NB, Elkjaer J, Dehlie B, Boysen K, Zaric D, Munksgaard A, Madsen JB, Oberg B, Khanykin B, Blemmer T, Yndgaard S, Perko G, Wang LP, Winkel P, Hilden J, Jensen P, Salas N. Effect of perioperative beta blockade in patients with diabetes undergoing major non-cardiac surgery: randomised placebo controlled, blinded multicentre trial. BMJ. 2006; 332: 1482.
11. Devereaux PJ, Beattie WS, Choi PT, Badner NH, Guyatt GH, Villar JC, Cina CS, Leslie K, Jacka MJ, Montori VM, Bhandari M, Avezum A, Cavalcanti AB, Giles JW, Schricker T, Yang H, Jakobsen CJ, Yusuf S. How strong is the evidence for the use of perioperative beta blockers in non-cardiac surgery? Systematic review and meta-analysis of randomised controlled trials. BMJ. 2005; 331: 313–321.
12. Lindenauer PK, Pekow P, Wang K, Mamidi DK, Gutierrez B, Benjamin EM. Perioperative beta-blocker therapy and mortality after major noncardiac surgery. N Engl J Med. 2005; 353: 349–361.
13. Fleisher LA, Beckman JA, Brown KA, Calkins H, Chaikof E, Fleischmann KE, Freeman WK, Froehlich JB, Kasper EK, Kersten JR, Riegel B, Robb JF, Smith SC Jr, Jacobs AK, Adams CD, Anderson JL, Antman EM, Buller CE, Creager MA, Ettinger SM, Faxon DP, Fuster V, Halperin JL, Hiratzka LF, Hunt SA, Lytle BW, Nishimura R, Ornato JP, Page RL, Tarkington LG, Yancy CW. ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery). Anesth Analg. 2008; 106: 685–712.
14. Devereaux PJ, Yang H, Yusuf S, Guyatt G, Leslie K, Villar JC, Xavier D, Chrolavicius S, Greenspan L, Pogue J, Pais P, Liu L, Xu S, Málaga G, Avezum A, Chan M, Montori VM, Jacka M, Choi P. Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled trial. Lancet. 2008; 371: 1839–1847.[CrossRef][Medline]
15. Fleisher LA, Poldermans D. Perioperative beta blockade: where do we go from here? Lancet. 2008; 371: 1813–1814.[CrossRef][Medline]
16. Shammash JB, Trost JC, Gold JM, Berlin JA, Golden MA, Kimmel SE. Perioperative beta-blocker withdrawal and mortality in vascular surgical patients. Am Heart J. 2001; 141: 148–153.[CrossRef][Medline]
17. Hoeks SE, Scholte Op Reimer WJ, van Urk H, Jorning PJ, Boersma E, Simoons ML, Bax JJ, Poldermans D. Increase of 1-year mortality after perioperative beta-blocker withdrawal in endovascular and vascular surgery patients. Eur J Vasc Endovasc Surg. 2007; 33: 13–19.[CrossRef][Medline]
18. Heeschen C, Hamm CW, Laufs U, Snapinn S, Bohm M, White HD. Withdrawal of statins increases event rates in patients with acute coronary syndromes. Circulation. 2002; 105: 1446–1452.
19. Colivicchi F, Bassi A, Santini M, Caltagirone C. Discontinuation of statin therapy and clinical outcome after ischemic stroke. Stroke. 2007; 38: 2652–2657.
20. Brett A. Coronary assessment before noncardiac surgery: current strategies are flawed. Circulation. 2008; 117: 3145–3151.
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