Alberto Margonato and Stefano Gerosa have provided us with a thorough and well-written review addressing a central question in perioperative medicine: Do beta-blockers sufficiently protect patients from the development of perioperative cardiovascular complications? The value of beta-blockers has been debated for many years, and the relevance of this topic will only expand. Cardiac complications are the leading cause of perioperative morbidity and mortality [1]; in 2020, the number of patients eligible for surgery will increase by 25% [2]. This review provides readers with a clear insight into (1) mechanisms of action and characteristics of beta-blockers and (2) pathophysiology of perioperative cardiovascular complications. It also is an extended literature overview of beta-blocker use in noncardiac and vascular surgery.
Two randomized controlled trials evaluating the protective value of beta-blockers, which are discussed thoroughly, are the Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography-I (DECREASE-I) trial performed in Rotterdam [3] and the multicenter PeriOperative ISchemic Evaluation (POISE) trial [4]. In the DECREASE-I trial, vascular surgery patients were treated with the highly selective beta₁-adrenoreceptor antagonist bisoprolol titrated to achieve a heart rate between 60 to 65 beats per minute. Bisoprolol treatment reduced the occurrence of peri- and postoperative cardiovascular complications [3,5]. The DECREASE-I trial included high-risk vascular surgery patients; however, promising results in the DECREASE-IV trial show beneficial effects of bisoprolol treatment in intermediate-risk patients as well [6]. The incidence of stroke was comparable between patients receiving bisoprolol or placebo. In the POISE trial, patients were treated with a relatively high dosage of the long-acting beta-blocker metoprolol succinate. Metoprolol succinate did lower the incidence of myocardial infarction; however, this benefit was outweighed by an increased incidence of stroke and death.
Different treatment protocols of the DECREASE-I trial, POISE trial, and other studies are elegantly summarized by the authors and differ in (1) initiation time of therapy, (2) beta-blocker type, (3) mode of administration, and (4) risk profile of the patients. Margonato and Gerosa note that the question of whether beta-blocker use is effective in reducing preoperative cardiovascular complications without excessive side-effects has not been answered yet. They propose that a future randomized, double-blind, placebo-controlled trial is needed, which should include a sufficient number of patients with a revised cardiac risk index of at least ≥2, who are scheduled for vascular and major noncardiac surgery.
We propose low-dose treatment with a highly selective long-acting beta-blocker, initiated at least 1 month prior to surgery. Up-titration according to tolerance to obtain heart rates between 65 and 70 beats per minute could demonstrate maximal protection of beta-blockers without overtreating the patients. Intraoperatively, the ultrashort beta-blocker esmolol, administered via a continuous infusion, could be considered as well to maximally prevent the occurrence of adverse myocardial events. A randomized double-blind placebo-controlled trial of this kind could provide the final answer to the question: do beta-blockers in noncardiac surgery really work?

REFERENCES

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2. Mangano DT. Perioperative medicine: NHLBI working group deliberations and recommendations. J Cardiothorac Vasc Anesth 2004;18:1-6.

3. 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. Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography Study Group. N Engl J Med 1999;341:1789-1794.

4. Devereaux PJ, Yang H, Yusuf S, et al. Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled trial. Lancet 2008;371:1839-1847.

5. Feringa HH, Bax JJ, Schouten O, Poldermans D. Protecting the heart with cardiac medication in patients with left ventricular dysfunction undergoing major noncardiac vascular surgery. Semin Cardiothorac Vasc Anesth 2006;10:25-31.

6. Dunkelgrun M, Boersma E, Koopman-Van Gemert A, et al. Fluvastatin and bisoprolol for cardiac risk reduction in intermediate-risk patients undergoing non-cardiovascular surgery; a randomised controlled trial. Eur Heart J 2008;29(suppl):602-603.