Original article
Prophylaxis Against Atrial Fibrillation after Cardiac Surgery: Beneficial Effect of Perioperative Metoprolol

https://doi.org/10.1016/j.hlc.2012.12.017Get rights and content

Abstract

Introduction

Multiple agents have been investigated to prevent atrial fibrillation (AF) after cardiac surgery. Several studies have investigated the use of β-blockers such as metoprolol or amiodarone with promising results. We aimed to investigate perioperative pharmacologic prophylaxis against AF using metoprolol, and amiodarone in combination with metoprolol.

Methods

We conducted a prospective, randomised, single-blind, controlled pilot study in patients undergoing elective cardiac surgery. Subjects were randomised pre-operatively to one of three treatment groups: standard therapy (control) or metoprolol (5 mg IV over 5 min on commencement of bypass then 5 mg IV qid for 24 h then 25–50 mg tds orally until discharge) or amiodarone (300 mg over 1 h starting shortly after the commencement of bypass, then 900 mg over 24 h then 400 mg orally tds until discharge) plus metoprolol as above. Patients had ECG monitoring for the occurrence of AF for six days or until discharge.

Results

Two hundred and fifteen patients were enrolled. Between-group differences in AF in an intention-to-treat analysis were not significant: control 34% (23–45%), metoprolol 35% (24–46%), combined 22% (12–33%) (p = 0.21). However 87 patients (40%) did not receive the assigned treatment mainly due to side effects, especially bradycardia. The remaining 128 patients were analysed on a per-protocol basis with the overall difference between the three groups bordering on significance: control 34% (23–45%), metoprolol 26% (9–43%), combined 11% (0–23%) (p = 0.06). Logistic regression analysis, correcting for age and gender, was used to separate the individual effects of metoprolol and amiodarone in the presence of metoprolol which showed that compared to control there was a significant effect of metroprolol on AF incidence (O.R. 0.31 (0.10–0.99), p = 0.048) but not of amiodarone (O.R. 0.97 (0.19–5.02), p = 0.97).

Conclusions

(1) Perioperative metoprolol but not amiodarone itself in combination with metoprolol is associated with a significant reduction in postoperative AF.

(2) Perioperative administration of metoprolol and combination of metoprolol with amiodarone is associated with a high incidence of side effects, especially bradycardia.

(3) Further studies are indicated to confirm these preliminary findings but in the meantime it would not be unreasonable to implement the use of perioperative metoprolol for routine prophylaxis of AF.

Introduction

Postoperative atrial fibrillation (AF) is the most common complication after cardiac surgery, occurring in 10–65% of patients [1], with an incidence of 30% in coronary artery bypass grafting (CABG), 40% in valve surgery, and 50% in combined CABG and valve surgery. The peak time of occurrence is 48–72 h following cardiopulmonary bypass [2]. Clinical consequences include reduced cardiac output, lengthened hospitalisation, an increase in the risk of cerebral thromboembolism and in many cases the need for systemic anticoagulation [3], [4]. A subgroup of patients with rapid ventricular response may become acutely haemodynamically unstable, requiring rapid intervention with DC reversion. Thus the occurrence of AF translates to an increase in the overall cost of hospitalisation [5]. Numerous agents and various therapeutic regimens have been trialled in the treatment of established AF with varying degrees of clinical efficacy [3], [6], [7], [8], [9].

Medications including digoxin, verapamil, diltiazem and procainamide [10] have failed to demonstrate any consistent benefit. Beta-blockers – both selective and non- selective – including propanolol, metoprolol, sotolol, atenolol and lenedilol have been shown to significantly reduce the incidence of AF when given prophylactically. Patients most likely to benefit are those who have been receiving beta-blockers preoperatively [11]. Class III (Vaughn–Williams) anti-arrhythmic agents such as amiodarone have been shown to be effective prophylactically when prescribed either: orally for a seven day pre-operative period [8], intravenously in high dose at the time of surgery [7], or for 96 h postoperatively [6]. Results from the AFIST trial indicated that a combination of beta blockade with four–five days of preoperative amiodarone is effective in minimising the incidence of post operative AF [4]. One meta-analysis suggested that either of these therapies is equally effective in reducing the risk of post operative AF [11].

The combination of amiodarone and metoprolol has also been shown to be effective and safe in several trials [12], [13], [14]. But whether a perioperative combination of amiodarone and beta blocker therapy is superior to metoprolol monotherapy is not clear [4], [13], [14], [15].

We therefore set out to determine the feasibility and clinical efficacy of using perioperative metoprolol with or without amiodarone for the prophylaxis of postoperative AF in a group of patients undergoing elective cardiac surgery. The primary aim of the study was to compare the rates of AF with prophylaxis by metoprolol or amiodarone plus metroprolol with no treatment (control). Secondary aims were to observe the effects of these treatments on mortality and length of hospital stay.

Section snippets

Study subjects

The study population comprised 215 (170 male, 45 female) patients over the age of 18 years, and in normal sinus rhythm preoperatively who were referred for cardiac surgery at the Alfred Hospital. Patients were required to have an ejection fraction of greater than 30% or not be in NYHA Class IV heart failure. Patients were excluded if they had thyroid disease, an elevated serum aspartate aminotransferase or alanine aminotransferase or gastrointestinal disorders which may have interfered with

Patient population

A total of 215 participants were enrolled in the trial and randomised to the three treatment arms. Twenty–four of these participants were operated upon off pump. None of the study population required inotropes or digoxin prior to surgery. Patients did not have significant asthma or bronchial hyper-reactivity and all had a blood pressure of >90 mmHg at the start of the study. Prior to surgery no patients had any evidence of rhythm disturbances, sinus bradycardia (<50 beats per min),

Discussion

The primary aim of this pilot study was to assess the efficacy of metoprolol in preventing AF after cardiac surgery and whether its efficacy could be increased by the addition of amiodarone. In the study we encountered a high incidence of side effects, mainly hypotension and bradycardia which led to 58–64% of the patients in the treatment groups not receiving their allocated treatment. The intention to treat analysis showed no treatment effect. However, the per-protocol analysis after logistic

Conclusions

  • 1.

    Perioperative metoprolol but not amiodarone in combination with metoprolol is associated with a significant reduction in postoperative atrial fibrillation.

  • 2.

    Perioperative administration of metoprolol and combination of metoprolol with amiodarone is associated with a high incidence of side effects, especially bradycardia.

  • 3.

    Further studies are indicated to confirm these preliminary findings but in the meantime it would not be unreasonable to implement the use of perioperative metoprolol for routine

Acknowledgements

The authors acknowledge the advice and assistance of Professor Paul Myles in planning the study. The authors also acknowledge the advice, assistance and cooperation of the surgeons of the CJ Officer-Brown Cardiothoracic Surgery Unit and the work of the nurses in the intensive care unit at the Alfred Hospital.

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