Pre-operative beta-blockade is a widely accepted practice in patients having cardiac surgery, but in non-cardiac surgery use of perioperative beta-blockers is controversial. This is particularly true for patients at low risk of myocardial ischaemic events because of the risk of stroke.
Early data regarding perioperative beta-blockers in non-cardiac surgery included the DECREASE study, which randomised 112 high risk patients to Bisoprolol (initiated at least one week before surgery and continued for at least 30 days post-operatively) or placebo. (1) The primary study end-point of death from cardiac causes or nonfatal myocardial infarction occurred in 3.4% of the Bisoprolol group vs 34% of the placebo group. Based on these early data, perioperative beta-blockers were recommended for patients with untreated hypertension, known coronary disease or cardiac risk factors in the 1996 and the 2002 US guidelines. Further research –however- with larger randomised controlled trials (RCTs) has cast doubt on these early results and, moreover, in 2012 data from the DECREASE study have been withdrawn due to evidence of falsification.
Systematic review of 17 studies, including 16 RCTs, for the 2014 ACC/AHA guidelines found that perioperative beta-blockade initiated within one day of non cardiac surgery prevented non-fatal MI but increased risk of stroke, death, hypotension and bradycardia. (2) These results remained unchanged even after data from the DECREASE study were excluded.
Recent analysis of data from 326,000 individuals in the Veterans Health Administration has demonstrated that in patients with high cardiac risk, perioperative beta-blockade was associated with reduced 30-day mortality amongst patients having non cardiac surgery (OR 0.63%; 95% CI 0.43-0.93). However in patients with no cardiac risk factors, the reverse was true and beta-blockers were associated with higher 30-day mortality (OR 1.19; 95% CI 1.06-1.35). The cardiac risk factors included were renal failure, coronary artery disease, diabetes and surgery in a major body cavity (3).
The story of perioperative beta-blockade in non-cardiac surgery has oscillated and appears to have landed somewhere in the middle. Where do you stand on this?
(1) 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(24):1789-94.
(2) Wijeysundera, DN, Duncan D, Nkonde-Price C, et al. Perioperative beta blockade in noncardiac surgery: a systematic review for the 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014;130(24):2246-64.
(3) Friedell ML, Van Way CW, Freyberg RW, Almenoff PL. β-Blockade and operative mortality in noncardiac surgery: Harmful or helpful? JAMA Surg. 2015 (Epub ahead of print).
Cardiac events are a major cause of complications in non-cardiac surgery. The stress of surgery may trigger ischaemia so perioperative beta-blockade has been proposed to decrease myocardial oxygen consumption.
However, the clinical impact of perioperative beta-blockade remains unclear because of the controversial data available from clinical trials. The discrepancies in their results can be explained for differences in patient characteristics, risk of surgery and method of beta-blockade (timing, duration, type and dose).
The most recent European Guidelines on non-cardiac surgery (2014) recommend continuation of beta-blocker therapy in patients currently receiving the treatment (class of recommendation I, level of evidence A) but the preoperative initiation may be only considered for patients who have known ischaemic heart disease or myocardial ischaemia, or for patients scheduled for high-risk surgery and who have at least 2 clinical risk factors (class IIB, level of evidence B), avoiding initiation with high doses of beta-blockers (class III, level of evidence B).
As reported in the Cardionote, Friedell et al analyzed data from 119 Veterans Administration hospitals during five years (2008-2013). They found that the use of perioperative beta-blockade (a dose was ordered at any time between 8 hours before surgery and 24 hours postoperatively) was associated with reduced mortality rate only in patients at high risk whereas in patients with no cardiac risk factors this strategy resulted in a significantly increased risk of death.
The authors recognize several limitations in the study. First, there is no information about specific drug administered and, second, there is lack of information about timing of beta-blockade initiation. In our opinion, the beta-blockade group is heterogeneous, because it includes three groups of patients: (1) patients using perioperative beta-blockade as continuation of home medication, (2) patients starting drug before surgery and (3) patients receiving the first dose in the postoperative period (treatment of ischaemic complication?). The authors do not provide separate data about the outcome of patients that started beta-blockade in the preoperative period as a preventive strategy.
In conclusion, consistent with the current guidelines and this recent large series, a strategy of continuing preexisting beta-blockade therapy while considering cautiously its initiation in some high-risk patients scheduled for high-risk surgery avoiding high doses may be a reasonable approach. Further studies are needed to help guiding best practices in other patients and clinical settings as well as in selecting the best drug, dosing and timing.
Joint Expert Opinion by Dr Hector Bueno & Dr Roberto Martín-Asenjo