Interactive Cardiovascular and Thoracic Surgery 3:641-646(2004)
© 2004 European Association of Cardio-Thoracic Surgery
Best evidence topic - Cardiac general |
Are prophylactic ß-blockers of benefit in reducing the incidence of AF following coronary bypass surgery?
Savvas Omorphos,
Mohammed Hanif and
Joel Dunning*
Department of Cardiothoracic Surgery, Freeman Hospital, Freeman Road, Newcastle Upon Tyne NE7 7AZ, UK
* Corresponding author. Tel.: +44-780-154-8122. (E-mail: joeldunning{at}doctors.org.uk).
Received July 16, 2004;
accepted July 22, 2004
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Abstract
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A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether prophylactic beta-blockers effectively reduces the incidence of atrial fibrillation post-cardiac surgery. Altogether 113 papers were found using the reported search, of which 8 represented the best evidence on this topic. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses were tabulated. We conclude that prophylactic beta-blockers clearly reduce the incidence of AF with a number needed to treat of only seven to prevent one episode of AF. The optimal beta-blocker or the benefits to patients with impaired ejection fraction are less clear.
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1. Introduction
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A best evidence topic was constructed according to a structures protocol. This protocol is fully described in the ICVTS [1].
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2. Clinical scenario
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You are seeing a 75-year-old diabetic man with triple vessel disease, for whom you are going to perform triple vessel coronary arterial bypass tomorrow. He has been suffering with angina for the past 9 years but it has got progressively worse. His left ventricular ejection fraction is 45%.
You note that he is on 25mg of atenolol pre-operatively and his heart rate is 80 today. He reports that he has had palpitations occasionally in the past but not recently. You feel that he is almost destined to go into atrial fibrillation post-operatively but there is a wide variation in the hospital with regard to beta-blocker prophylaxis with some patients being changed to sotalol pre-operatively, some having atenolol started on the day after surgery, and many patients with any impairment of their ejection fraction having all beta-blockers withdrawn for at least 4 days. You wonder whether there is any consensus in the literature.
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3. Three-part question
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In [patients undergoing cardiac surgery] are [prophylactic ß-blockers] of benefit in reducing the incidence of [post-operative AF]?
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4. Search strategy
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Medline 1966–July 2004 using the OVID interface.
[cardiac surgery.mp OR exp thoracic surgery OR bypass.mp OR CABG.mp OR exp coronary artery bypass OR cardiopulmonary bypass.mp OR exp cardiovascular surgical procedures] AND [exp adrenergic beta-antagonists OR exp beta-blockers OR beta-adrenoceptor blocker.mp OR prophylactic drug therapy.mp] AND [exp atrial fibrillation OR post-operative AF.mp OR post-operative atrial fibrillation.mp OR supraventricular arrhythmia.mp OR supraventricular arrhythmias.mp].
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5. Search outcome
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A total of 113 papers were found from which five meta-analyses and systematic reviews represented the best evidence. In addition The American Heart Association guidelines were reviewed. Cross-checking reference lists and journal club suggestions provided an additional two papers. These papers are listed in Table 1.
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6. Results
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Andrews et al. [2] performed the first meta-analysis in this area. They found that 13 or 18 studies investigating the benefit of prophylactic beta-blockers showed a significant benefit in favour of giving prophylaxis. Pooling all these results showed a reduction in AF from 34% to 8.7% from studies involving 1549 patients. Interestingly no difference was shown when pre-operative beta-blocker studies were compared to post-operative studies. No benefit was shown in eight studies assessing either verapamil or digoxin as AF prophylaxis. They also showed that the mean ventricular rate was significantly lower in beta-blocked patients when they did go into AF, with a mean rate 24 bpm slower than controls. They did caution that most patients in these studies were young, male and had good ejection fractions and had been on beta-blockers pre-operatively.
Kowey et al. [3] in 1992 pooled data from seven studies containing 1418 patients, and found a reduction in AF from 20.2% to 9.8%. In addition, they pooled data from two studies containing 292 patients that looked at prophylaxis with both digoxin and beta-blockers and concluded that combination therapy was better than beta-blockers alone with a P value of less than 0.01.
Zimmer et al. [9] performed a meta-analysis of all anti-arrythmic strategies to look at the length of stay, costs, stroke and mortality. They found that there was an average 1 day less in hospital, and $1300 less in costs using an anti-arrythmic prophylactic strategy, although they showed no difference in stroke or mortality. Although only one study was in beta-blockers, they justified extrapolation to all strategies on the basis that all strategies had the same endpoint of reduction of AF, and this meta-analysis quantifies for the first time the benefits of reducing the incidence of post-operative AF.
Crystal et al. in 2002 [6] performed a comprehensive meta-analysis, including 52 RCTs on a variety of prophylactic therapies. They found that beta-blockers reduced AF from 33% to 19% from pooled data from 27 RCTs that recruited 3840 patients. This corresponds to a number needed to treat of 7. Pooling all strategies to reduce AF they found that hospital stay could be reduced by half a day, but no reduction in the incidence of stroke could be found. In sub-analyses they found that four trials with 900 patients compared sotalol with other beta-blockers and found that sotalol significantly reduced the incidence of AF compared with other beta-blockers. However, they caution that sotalol also has the potential to cause proarrythmic side effects despite this reduction in AF, but provide no figures to back this up.They also investigated the effect of either pre-operative or post-operative commencement of beta-blocker prophylaxis and found no difference between the two strategies. As a final note they found that both prophylactic amiodarone and biatrial pacing also significantly reduces the incidence of AF.
Wurdeman et al. [7] in 2002 compared studies investigating sotalol with studies investigating amiodarone. They found no studies that directly compared both drugs. They found that sotalol reduced the incidence of AF by 21.5% compared to a reduction of 14% with amiodarone, but this difference between the drugs was not statistically significant. In addition a significantly higher percentage of patients receiving sotalol had their treatment stopped due to side-effects. No differences in length of stay were found. They concluded that both drugs were comparable in terms of their efficacy in reducing AF but amiodarone had fewer side-effects.
Maisel et al. [5] performed a systematic review in 2001 and concluded that all patients should receive both pre-operative and post-operative beta-blockers prior to cardiac surgery, unless contraindicated, in which case amiodarone or biatrial pacing should be used. Of note they mainly quoted the meta-analysis from Andrews et al. in making these recommendations [2].
Ferguson et al. [8] performed a large retrospective analysis of the STS surgical database containing 629,877 patients to look at the mortality and morbidity associated with pre-operative beta-blocker use. This was not a randomized trial and therefore patients had not received beta-blockers randomly, so the authors used a propensity score for the risk of receiving a beta-blocker, derived from patient and centre-associated risk factors. After adjustment they found that there was a slightly lower mortality in the pre-operative beta-blocker group, and a lower incidence of stroke ventilation and renal failure. They also found that patients with an EF less than 30% had a slightly increased mortality. This study was also not considering the effect of reduction in AF but only the benefit of beta-blockers by any mechanism.
The American Heart Association [4] recommends that continuing beta-blockers and restarting them early post-op represents the optimal standard of care in coronary bypass graft surgery.
In summary, the results of five meta-analyses show that prophylactic beta-blockers clearly reduce the incidence of AF. In addition some benefits in terms of reducing length of stay, costs, mortality and morbidity have been shown in patients with a good ejection fraction, although the evidence for this is far less strong. In addition the benefits of pre-operative administration over early post-operative administration have not been clearly demonstrated or the relative benefits of any one beta-blocker over another.
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7. Clinical bottom line
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Prophylactic beta-blockers clearly reduce the incidence of AF with a number needed to treat of only 7 to prevent one episode of AF. The optimal beta-blocker or the benefits to patients with impaired ejection fraction are less clear.
doi:10.1016/j.icvts.2004.07.014
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References
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- Kowey PR, Taylor JE, Rials SJ, Marinchak A. Meta-analysis of the effectiveness of prophylactic drug therapy in preventing supraventricular arrhythmia early after CABG Am J Cardiol 1992;69:963-965.[CrossRef][Medline]
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- Ferguson Jr TB, Coombs LP, Peterson ED. Society of Thoracic Surgeons National Adult Cardiac Surgery Database. Pre-operative B-blocker use and mortality and morbidity following CABG surgery in North America J Am Med Assoc 2002;287(17):2221-2227.[Abstract/Free Full Text]
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Abstract
1. Introduction