Does taking Metoprolol before cardiac surgery reduce the incidence of post-op atrial fibrillation

Abstract

Postoperative atrial fibrillation (POAF) remains a prevalent supraventricular arrhythmia. PoAF has associated effects such as deteriorating hemodynamic, increased risk of stroke and increased probability of death. Beta-blockers have been recommended as effective intervention mechanism of preventing PoAF. Metoprolol is one such beta-blocker that is commonly administered to prevent the incidence of PoAF. The systematic review below entails an analysis of six clinical trials that explore the effectiveness of metoprolol. The analysis identifies reduced hospitalization length, reduced mortality and reduced financial burden as the beneficial impact associated with the administration of prophylactic. The small number of studies reviewed limits the validity of the conclusion warranting future large sample size research.

Introduction

Annually, approximately 750,000 cardiac surgery are performed globally with postoperative atrial fibrillation (PoAF) being the prevalent complications (George, et al., 2018). With the increasing proportion of elderly population globally, it’s expected that the number of cardiac surgeries would accelerate, consequently increasing the incidence of PoAF (George, et al., 2018). Existing epidemiological data suggest that incidence of PoAF after cardiac surgery remains a prevalent risk and detrimental sequelae that yields increased hospitalization days, substantial economic cost and increased morbidity and mortality (Crystal, et al., 2004). Systematic review findings by George, et al., (2018) demonstrate 20-50% incidence of PoAF in cardiac surgical patients

According to Lúcio, et al., (2004) PoAF is classified as a supraventricular arrhythmia delineated by inconsistent and rapid ventricular rate due to loss of atrial contraction which picks within the two days after the cardiac operation. The high atrial frequency causes an irregular contraction frequency and irregular electrical activation of the ventricles. There are five types of atrial fibrations distinguished by the duration of the arrhythmia, which includes; paroxysmal, long-standing, persistent, first diagnosed and permanent atrial fibrillation.

Several predisposing factors including previous history of atrial fibrillation (AF), valvular heart surgery, chronic renal failure, chronic obstructive pulmonary condition, rheumatic heart disease, reduced left ventricular ejection fraction, diabetes mellitus, and advanced age have been identified to accelerate the incidence of PoAF (George, et al., 2018). Although PoAF maybe a temporary condition, it’s associated with multiple medical complications. Particularly, valvular heart surgeries are reported to have a higher risk of PoAF. PoAF is linked to increased post-surgery risk of chronic conditions such as stroke, heart failure and myocardial infarction (George, et al., 2018). Turagam, et al., (2015)reports an estimated 30-40% prevalence rate of AF among patients undergoing cardiac surgery.

Literature Review

Multiple pharmacological approaches have been developed to prevent postoperative AF (PoAF) including the Metoprolol to post-surgery (Turagam, et al., 2015). Clinical evidence of intervention mechanisms of preventing incidences of PoAF identifies that the approaches have a counteracting effect on PoAF on triggering factors. The underlying mechanisms or preventing PoAF centered around reducing inflammation with steroids, statins, polyunsaturated fatty acids or colchicine; controlling the neurohumoral system through amiodarone, angiotensin-converting enzyme inhibitor beta-blockers; reducing the myocardial energy demands with beta- blockers or reducing oxidative stress with acetylcysteine or ascorbate (Turagam, et al., 2015).

Use of preoperative beta-blockers such as Metoprolol is one intervention that controls the neurohumoral system by diminishing the demand of myocardial oxygen and blunting the inotropic and chronotropic of a surge of catecholamine (Turagam, et al., 2015). The B blocker treatment has been recommended by the European Society of Cardiology and the American Heart Association as a first treatment intervention for preventing PoAF (George, et al., 2018). However, findings on the efficacy of metoprolol remain elusive (Turagam, et al., 2015) providing a research gap for the current study.

Existing literature explores the effectiveness of administration of Metoprolol to post-cardiac surgery patients (Turagam, et al., 2015). Extant research has limitedly reviewed the effectiveness underlying the use of preoperative administration of Metoprolol to minimize the incidence of PoAF (Turagam, et al., 2015), hence, the motivation of the current research. In this review, I explore the randomized controlled trials behind the use of metoprolol as a pharmacological intervention of preventing PoAF

Methods

The search was undertaken using databases such as the PubMed, Cochrane Central Database and Google Scholar. The search terms used to identify the studies include metoprolol, Atrial fibrillation (AF), Cardiac Surgery. A limited search of “Metoprolol and Atrial fibrillation” yields 259 hits PubMed and custom range of 2000- 2019 search on google scholar yielded 16,800 hits. Since searching of “Metoprolol and Atrial fibrillation” on the Cochrane Central Database yielded limited hits, and the publications on the PubMed are both included in the google scholar and Cochrane Central Database, the papers constrained to publications in PubMed. Studies were included if they met certain criteria; i) randomized trials ii) a number of patients is not less than 200, iii) metoprolol was administered iv) rich statistical analysis of the results. The abstracts, methods, result and conclusion sections of the identified papers were analyzed to identify the relevance of the findings to the current review.

Results

Six papers were shortlisted from the database which entails randomized clinical trials of the use of preoperative administration of metoprolol in cardiac surgery patients. Table 1 below presents a summary of the statistics of the shortlisted studies.

Table 1: Summary of clinical trials examining the effectiveness of Metoprolol on PoAF

Study

Design

Sample Size

Type of Cardiac Surgery

Outcomes

Lucio et al.. (2004)

Open Randomized Study

200

coronary artery bypass graft

Respective incidences of PoAF: 11% (Metoprolol group) and 24% (control group)(P=0.02).

Crystal et al., (2004)

Randomized Controlled Trial

1000

Elective open heart surgery

Incidence of PoAF in metoprolol group decreased 40.1% to 29.6% and increased from 35% to 38.5% in control group

Hjalmarson et al (2000)

Randomized Controlled Trial

3991

functional class II to IV,

significant 31% decline in total mortality in the metoprolol group

Halonen et al., (2006)

Randomized Controlled Trial

240

Coronary artery bypass graft

Aortic valve replacement

Lower incidence PoAF in intravenous group (16.8%) relative to than in the control (28.1%) P0.036)

Yang et al (2006)

Randomized Controlled Trial

496

abdominal aortic surgery

Infrainguinal

Axillofemoral revascularizations

Incidence of PoAF in intervention group 10.2%, 95% CI

Incidence of PoAF in the control group (12%, 95% CI).

Acikel et al (2008)

Randomized Controlled Trial

110

coronary artery bypass grafting

36% incidence of PoAF in the metoprolol group

16% incidence of PoAD in the carvedilol group

The results from the above clinical trials demonstrate that preoperative administration of metoprolol significant reduced the incidence of PoAF which ultimately yields two positive effects; reduced the mortality rate and reduced financial cost. Hjalmarson et al (2000) identified that administration of metoprolol substantially reduced the risk of PoAF and other subsequent complications. The randomized controlled trial identified reduced total mortality by 31 % (95% CI) and 20 % (CI) reduction number of hospitalization days due to post-surgery complications. The statistical analysis by Hjalmarson et al (2000) identified that deaths among the heart transplant patients reduced by 32% while the emergency admission reduced by 32% as a consequence of pre-operative metoprolol. The robustness of the clinical trial by Hjalmarson et al (2000) validates the research findings on the contribution of metoprolol in reducing the economic burden associated with PoAF by reducing the days of hospitalization, or hospital readmission due to worsening cardiac complications.

The clinical trial by Crystal et al., (2004) of 100 patients with similar AF history, age and sex identifies a 8% (99% CI) reduced risk of PoAF associated to administration of prophylactic metoprolol and an increased risk of PoAF by 3.3 % (97% CI) among the placebo group. PoAF increases the length of admission in the Intensive Care Unit (ICU) (Crystal et al., 2004). According to Crystal et al., (2004), failure to administer beta-blockers results prior to cardiac surgery yields a decline of the cardiac index and a risk chronotopic effect for beta-blockers administered after the cardiac surgery. The patients in the control group reported an increased length of stay in ICU from 158 hours to 183.4 hours demonstrating the prophylactic metoprolol affects. Consequently, the placebo group had higher associated hospital cost demystifying the essentiality of prophylactic metoprolol in cardiac surgeries.

The incidence of atrial fibrillation is the prevalent complication observed in cardiac surgeries. The incidence is higher in elderly patients who form the majority of cardiac surgery patients (Lucio et al., 2004). Exploring an open randomized clinical trial of 200 patients, Lucio et al.. (2004) identify a higher incidence of PoAF of 24% (95% CI) in the placebo group and an 11 % (95% CI) incidence risk in the metoprolol group. Lucio et al.. (2004) observe that PoAF is reported between 2nd to 4th day after the surgery with a majority of the incidences peaking on the 2nd day. The clinical trial by Lucio et al.. (2004) identified several undesired symptoms associated with the administration of metoprolol which includes heart failure, hypotension, sinus bradycardia and, bronchospasm. Consistent with the earlier studies Lucio et al., (2004) findings supports the existing clinical evidence on the beneficial prophylactic effect of beta-blockers. As the elderly population increases globally increasing the population of cardiac patients, Lucio et al., (2004) accentuate efficacy of metoprolol in the increasing high-risk elderly patients group.

Yang et al (2006) extend monitoring of the effect of prophylactic effect of metoprolol to a 6 months’ period. Consistent with the earlier studies, Yang et al (2006) report a lower incidence of PoAF on the intervention group (10.2%, 95% CI) compared to the control group (12%, 95% CI). The clinical trial, however, doesn’t indicate any difference after monitoring the effectiveness of metoprolol over a period of 6 months demonstrating that metoprolol doesn’t delay the prevalence of PoAF. Comparative analysis of the efficacy of metoprolol and carvedilol by Acikel et al (2008) indicates although metoprolol reduces the incidence of PoAF, its efficacy is lower compared to other beta blockers such as carvedilol. Acikel et al (2008) randomized trial of 110 patients identifies 36% incidence of PoAF in the metoprolol group compared t0 16% of PoAF in the carvedilol group.

While research has centered on the comparative efficacy of metoprolol, limited research focuses on the form of its administration (Halonen, et al., 2004). Cardiopulmonary perfusion affects the absorption of metoprolol subsequently affecting the drug’s efficacy in preventing PoAF (Halonen, et al., 2004). The randomized controlled trial of 240 patients scheduled for cardiac surgery identified that a lower incidence of PoAF when intravenous administration of metoprolol. PoAF Halonen, et al., (2004) remotes a 28% incidence of PoAF in patients where metoprolol was orally administered and a 16.8% incidence of PoAF where metoprolol was intravenously administered.

Conclusion

The systematic review of findings six studies illustrates that the preoperative administration of metoprolol may effectively attenuate the incidence of PoAF that subsequently reduces the length of hospitalization, financial burden, and the morbidity and mortality rate. The analysis further reveals that intravenous administration, as opposed to oral administration, increases the efficacy of metoprolol. Given that the review considered six studies which arguably is a limited sample size, the conclusion may overestimate or underestimate the incidence of PoAF resulting in bias. A further systematic review exploring a larger sample size would validate the current conclusion.

References

Acikel, S., Bozbas, H., Gultekin, B., Aydinalp, A., Saritas, B., Bal, U., . . . Ozin, B. (2008). Comparison of the efficacy of metoprolol and carvedilol for preventing atrial fibrillation after coronary bypass surgery. International Journal of Cardiology, 108-113.

Crystal, E., Thorpe, K., Connolly, s., Lamy, A., Cybulsky, I., Carroll, S., . . . Gent, M. (2004). Metoprolol prophylaxis against postoperative atrial fibrillation increases length of hospital stay in patients not on pre-operative b blockers: the b blocker length of stay (BLOS) trial. American Heart Journal, 941-942.

George, P., Varkey, A., A, N., Mateti, U., Gopalakrishnan, M., & Theempalangad, R. (2018). Incidence of atrial fibrillation after cardiac surgery and its pharmacological management. Acta Med Int, 58-62.

Halonen, J., Loponen, P., Ja¨rvinen, O., Karjalainen, a., Parviainen, I., & Halonen, P. (2010). Metoprolol Versus Amiodarone in the Prevention of Atrial Fibrillation After Cardiac Surgery A Randomized Trial. Ann Intern Med, 703-709.

Hjalmarson, A., Goldstein, S., Fagerberg, B., Wedel, H., Waagstein, F., Kjekshus, J., . . . Gottlieb, S. (2000). Effects of controlled-release metoprolol on total mortality, hospitalizations, and well-being in patients with heart failure: the Metoprolol CR/XL Randomized Intervention Trial in congestive heart failure (MERIT-HF). MERIT-HF Study Group. JAMA, 1295-1302.

Lúcio, d. A., Flores, A., Blacher, C., Leães, P., Lucchese, F., & Ribeiro, o. (2004). Effectiveness of metoprolol in preventing atrial fibrillation and flutter in the postoperative period of coronary artery bypass graft surgery. Arq. Bras. Cardiol.

Turagam, M., Downey, F., Kress, D., Sra, J., Tajik, J., & Jahangir, A. (2015). Pharmacological strategies for prevention of postoperative atrial fibrillation. Expert Rev Clin Pharmacol., 233-250.

Yang, H., Raymer, K., Butler, R., Parlow, J., & Roberts, R. (2006). The effects of perioperative beta-blockade: results of the Metoprolol after Vascular Surgery (Mavs) study, a randomized controlled trial. American Heart Journal, 983-990.

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