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EDITORIALS: Stephen Bolsin, Mark Colson, and Myles Conroy blockers and statins in non-cardiac surgery BMJ 2007; 334: 1283-1284 [Full text]

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Perioperative beta blockade for high risk vascular patients

Adam C Pichel   (25 June 2007)

The routine use of beta-blockade and statin therapy to prevent cardiac complications in patients undergoing non-cardiac surgery.

Andrew J Turley, Michael J Stewart, Gerry Danjoux   (12 July 2007)

Perioperative beta blockade for high risk vascular patients 25 June 2007
Adam C Pichel, Consultant Anaesthetist Department of Anaesthesia, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WL Send response to journal: Re: Perioperative beta blockade for high risk vascular patients	Bolsin, Colson and Conroy report that the benefit of perioperative beta blockade remains unclear. However there is evidence of a benefit for those who are at greatest risk of an adverse cardiac event following vascular surgery. The recent studies to which they refer did not look at high risk patients. The diabetic postoperative mortality and morbidity study (1)(DIPOM) from Denmark showed no benefit nor significant harm from perioperative beta blockade. One must consider the low number of cardiac events in this study, reflecting the fact that they were not patients at significant risk. A high proportion underwent low risk procedures, and less than 35% were considered procedures that carry a high risk owing to a large anticipated stress repsonse to surgery. The DECREASE-1 trial (2) commenced beta blockers weeks in advance of vascular surgery and increased the dose of beta blocker if the patient's resting heart rate was greater than 60 bpm. This titration again occured weeks prior to surgery. This was not the case with the DIPOM trial, with many starting metoprolol the day before surgery and only continued for a maximum of 8 days after surgery. It is worth bearing in mind that most patients who are identified preoperatively(after non-invasive cardiac stress tests such as dobutamine stress echocardiography or stress myoview) as having significant ischaemic heart disease or LV dysfunction have a strong indication to start beta blockers irrespective of the need for non-cardiac surgery, and should stay on them for life. Another study qouted by the authors that does not support perioperative beta blockade was the POBBLE Trial (3). This also studied low risk patients, without a history of ishaemic heart disease undergoing vascular surgery. There was little chance of seeing a significant treatment effect in a study with 103 patients when the adverse cardiac event rate was so low, as compared to the DECREASE-1 trial. The POBBLE trial was originally powered to recruit 300 patients but this was clearly never attained. The retrospective observational cohort study of over 650,000 patients by Lindenauer (4) indicated that low and possibly intermediate risk patients did not benefit from perioperative beta blockade, but that those with a Revised Cardiac Risk Index of 3 or more had a reduced incidence of in-hospital mortality. The recent study from Holland which concluded that tight heart rate control does reduce myocardial ischaemia and Troponin T release following vascular surgery clearly shows the importance of an individualised approach. (5) On the current evidence if one is to use beta blockers to reduce significant numbers of cardiac events they must be titrated to effect and used in a high risk population. It is likely that those on chronic beta blocker therapy should have their beta blocker dose reviewed prior to major non-cardiac surgery due to the possibility of significant receptor up-regulation and a lower ischaemic threshold. The whole perioperative beta blockade debate is largely about screening the populations at greatest risk when they present for non-cardiac surgery and appropriately prescribing drugs known to have survival benefits. References (1)Juul AB, Wetterslev J, Gluud C, et al. Effect of perioperative beta blockade in patients with diabetes undergoing major non-cardiac surgery:randomised, placebo controlled, blinded multicentre trial. BMJ 2006;332:1482 (2)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 1999; 341:1789-94 (3)Brady AR, Gibbs JS, Greenhalgh RM, et al. Perioperative beta- blockade (POBBLE) for patients undergoing infra-renal vascular surgery: Results of a randomised double-blind controlled trial. J Vasc Surg 2005;41:602-609 (4)Lindenauer PK, Pekow P, Wang K, et al. Perioperative beta blocker therapy and mortality after major non-cardiac surgery. N Engl J Med 2005;353:349-361 (5) Feringa HH, Bax JJ, Boersma E, et al. High dose beta blockers and tight heart rate control reduce myocardial ischaemia and troponin T release in vascular surgery patients. Circulation 2006; 114[suppl 1]:344- 349. Competing interests: None declared
The routine use of beta-blockade and statin therapy to prevent cardiac complications in patients undergoing non-cardiac surgery. 12 July 2007
Andrew J Turley, Cardiology SpR James Cook University Hospital, Middlesbrough TS43BW, Michael J Stewart, Gerry Danjoux Send response to journal: Re: The routine use of beta-blockade and statin therapy to prevent cardiac complications in patients undergoing non-cardiac surgery.	The ACC/AHA guidelines classify non-cardiac surgery into categories of risk and further classify vascular from non-vascular procedures. This approach is crucial for a balanced discussion. The 2005 abdominal aortic aneurysm surgery national confidential enquiry into patient outcome and deaths reports 30-day mortality in elective open repair of patients with angina of 9% and 21% in those with LV systolic impairment, considerably higher than the 0.5-1% quoted by Bolsin et al for all comers undergoing non-cardiac surgery1. Traditionally pre-operative assessment concentrates on non-invasive evaluation of cardiac function. Appropriate risk stratification with either cardiopulmonary exercise testing (CPX) or dobutamine stress echo (DSE) can identify high-risk populations. CPX testing objectively assesses ventricular function through anaerobic threshold (AT), the point at which aerobic metabolism is supplemented by anaerobic metabolism. A low AT is associated with significantly increased mortality rates in patients undergoing major non-vascular intra-abdominal surgery2. DSE identifies and quantifies the presence and extent of reversible myocardial ischaemia. The incidence of cardiac causes of death and non-fatal myocardial infarction is significantly reduced by the peri-operative use of bisoprolol in high-risk patients undergoing major vascular surgery targeted on the basis of a high risk DSE result3. As coronary revascularisation prior to major surgery does not appear to significantly impact upon peri-operative mortality,4 medical therapy to reduce risk in these patients is particularly important. Evidence from non-selective studies should not be used to argue against studies of higher risk populations. Strategies to identify these high-risk patients are needed rather than a treat all (or not treat at all) policy. Recruitment to large scale, adequately powered, multinational studies is difficult but achievable as shown by the statin and ACE-inhibitor trials. These agents reduce cardiovascular complications in patients with or at high-risk (patients with peripheral vascular disease or diabetes) of developing ischaemic heart disease. Statin therapy is extremely safe with an extensive and well documented favourable safety profile5. If there is any potential for benefit and an indication for long term use what possible reasons exist to withhold their use? References 1. Bolsin S, Colson M, Conroy M. Beta blockers and statins in non- cardiac surgery. BMJ 2007;334(7607):1283-4. 2. Older P, Smith R, Courtney P, Hone R. Preoperative evaluation of cardiac failure and ischemia in elderly patients by cardiopulmonary exercise testing. Chest 1993;104(3):701-4. 3. Poldermans D, Boersma E, Bax JJ, Thomson IR, van de Ven LL, Blankensteijn JD, et al. 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(24):1789-94. 4. McFalls EO, Ward HB, Moritz TE, Goldman S, Krupski WC, Littooy F, et al. Coronary-artery revascularization before elective major vascular surgery. N Engl J Med 2004;351(27):2795-804. 5. Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 2005;366(9493):1267-78. Competing interests: None declared