Prevention of atrial fibrillation or flutter by acebutolol after coronary bypass grafting

Prevention of Atrial Fibrillation or Flutter by Acebutolol After Coronary Bypass Grafting PATRICK DAUDON, MD, THIERRY CORCOS, MD, IRADJ GANDJBAKHCH, MD, JEAN-PIERRE LEVASSEUR, MD, ANNIK CABROL, MD, and CHRISTIAN CABROL, MD

Supraventricular tachyarrhythmias are common after coronary artery bypass graft surgery (CABG) and may have deleterious hemodynamic consequences. To determine if acebutolol, a cardioselective/~-blocking drug, prevents such tachyarrhythmias after CABG, 100 consecutive patients, aged 30 to 77 years (mean 4- standard deviation 53 :E 9), were entered into a randomized, controlled study; Exclusion criteria were: contraindications to /~-blocking drugs, left ventricular aneurysm, major renal failure, history of cardiac arrhythmia and cardiac arrhythmia during the immediate postoperative period. From 36 hours after surgery until discharge (usually on the seventh day), 50 patients were given 200 mg of acebutolol (or 400 mg if weight was more than 80 kg) orally twice a day (dosage then modified to maintain a heart rate at rest between 60

and 90 beats/min). The 50 patients in the control group did not receive/~-blocking drugs after CABG. The 2 groups were comparable in angina functional class, ejection fraction, number of diseased vessels, antianginal therapy before CABG, number of bypassed vessels and duration of cardiopulmonary bypass. All patients were clinically evaluated twice daily and had continuous electrocardiographic monitoring and daily electrocardiograms. A 24-hour continuous electrocardiogram was recorded in the last 20 patients. Atrial tachyarrhythmias developed in 20 patients (40%) in the control group (17 patients had atrial fibrillation and 3 patients atrial flutter), but in none in the acebutolol group (p <0.001). This study reveals the efficacy of acebutolol in prevention of supraventricular tachyarrhythmias after CABG. (Am J Cardiol 1986;58:933-936)

S

potent B-blocking properties. 15,1B We evaluated the efficacy and safety of acebutolol in the prophylactic treatment of supraventricular tachyarrhythmias after CABG.

upraventricular tachyarrhythmias frequently complicate the postoperative course of patients undergoing coronary artery bypass grafting {CABG}; they can occur in 1I% to 100% of such patients.H3 These tachyarrhythmias may have deleterious hemodynamic effects and may require urgent drug therapy or even electric cardioversion. Their higher frequency in patients ~:wh~ have B-blockade therapy discontinued before CABG suggests that B-blockade withdrawal contributes to the high incidence of postoperative arrhythmias. 5,7,8,14 Acebutolol is a cardioselective fladrenoceptor blocking agent with membrane-stabilizing activity and moderate intrinsic sympathomimetic activity. It has a relatively shoi~thalf-life {4 ± I hours}, but its acetylated metabolite, diacetolol, also has

Methods Patients: One hundred patients undergoing elective CABG without additional cardiac surgical procedures (such as valve replacement or ventricular aneurysmectomy} were included. Patients were excluded if they had any of the following: (1} contraindication to B" blocking drugs, such as second- or third-degree atrioventricular block, bronchial asthma, severe chronic Obstructive lung disease, diabetes mellitus requiring drug therapy or suspected variant angina; (2} left ventricular aneurysm; (3) maj Or renal failure; (4} history of cardiac arrhythmias; (5} cardiac arrhythmias during the immediate (36 hours) postoperative period; and {6} low cardiac output still requiring catecholamine support at 36 hours after surgery. Study design: All patients received their antianginal therapy at full dose until the operation, including the morning of surgery. Patients included in the study

From the Department of Cardiovascular Surgery, H6pital de la Piti~, and the universit~ Pierre et Marie Curie, Paris, France. Manuscript received FebrUary 24, 1986; revised manuscript received June 23, 1986, accepted July 2, 1986. Address for reprints: Patrick Daudon, MD, Service de Chirurgie Cardio-vasculaire, H6pital de la Piti~; 83, Boulevard de l'H6pitai, 75651 Paris C6dex 13, France.

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934

ACEBUTOLOL FOR ATRIAL FIBRILLATION/FLUTTER

TABLE I

Clinical, Angiographic and Surgical Characteristics of Patients Control Group

Age (yr) Sex (F/M) Angina functional class (n)

I

Acebutolol Group (n -- 50)

p Value

(n = 50) 56 4- 9 4/46

51 -4- 8 1/49

<0.01 NS

3

II III IV Preoperative/~ blocker (n) Ejection fraction (%) CAD (n) 1 vessel 2 vessel 3 vessel Left main No. of diseased arteries No. of grafts Duration of cardiopulmonary bypass (min)

1 34 13 2 37 59 4- 12

26 16 5 35 61 4- 11

Perioperative infarction (n)

NS

NS NS

8

9 14 27 2 2.4 4- 0.8 2,4 4- 0.8

2,3 4- 0.7 2.3 4- 0.8

NS

77 4- 33

76 4- 31

NS

18 24

NS

4

1

NS

CAD = coronary artery disease; NS = difference not significant.

TABLE II Time of Occurrence of Postoperative Supraventrlcular Tachyarrhythmlas in the Control Group Postoperative Day of Occurrence Type

To~l 1

2

3

4

5

6

7

8

9

2

6

3

2

2

-

1

1

17

-

-

2

-

1

-

-

-

3 20

Atrial fibrillation (no. of pts) Atrial flutter (no. of pts)

were randomly assigned to either the control group or the acebutolol group at 36 hours after the procedure. In patients in the acebutolol-treated group, the drug was administrated orally twice daily from the thirty-sixth hour until discharge {usually on the seventh day}. The acebutolol dose was initially 200 mg {or 400 mg if patient weighed more than 80 kg} and then modified to maintain a heart rate at rest between 60 and 90 beats/ min. The 50 patients in the control group did not receive fl-blocking drugs after CABG. Perioperative myocardial infarction was diagnosed if serial electrocardiograms showed new Q waves or loss of R-wave voltage or if cardiac isoenzyme levels were abnormally elevated. Electrocardiographic monitoring: All patients underwent postoperative electrocardiographic {ECG} monitoring for the duration of their hospital stay. A standard 12-lead electrocardiogram was recorded daily and m o r e often if clinically indicated. Nurses were instructed to record all arrhythmias. A 24-hour ECG Holter tracing was recorded on the second or third postoperative day in the last 20 patients using an ELA Medical 2124 recorder; these tapes were scanned and analyzed with an Oxford Medilog analyzer. Atrial premature beats were not evaluated.

Statistical analysis: Comparison of patient characteristics and comparison of the incidence of supraventricular tachyarrhythmias in the 2 groups were made using the Student t test for continuous variables and the chi-square test for discrete variables.

Results Clinical, angiographic and surgical characteristics of patients are listed in Table I. Except for age, which was slightly but significantly lower in the acebutolol group {51 :t= 8 vs 56 ± 9 years, p <0.01}, there were no differences in preoperative variables such as sex, angina functional class {Canadian Cardiovascular Society Classification} and fl-blockade therapy. Similarly, the 2 groups were indistinguishable with regard to preoperative left ventricular ejection fraction, number of diseased coronary vessels, number of coronary bypass grafts per patient and duration of cardiopulmonary bypass. There was only 1 perioperative myocardial infarction in each group. Twenty patients {40%} in the control group had supraventricular tachyarrhythmias {Table II}. Seventeen {34%} had atrial fibrillation and 3 {6%} atrial flutter. No paroxysmal supraventricular tachycardia occurred. In the acebutolol-treated group, no patient had a supraventricular tachyarrhythmia {p

November 1. 1986

TABLE III

THE AMERICAN JOURNAL OF CARDIOLOGY

Volume 58

935

Digoxln for PrevenUon of Supraventricular Tachyarrhythmlas (SVT) After Coronary

Bypass Surgery Patients with SVT Study

Control Group

Treated Group

p Value

26% 11% 15 % 72 %

6% 28% 2% 5%

<0.01 <0.05 <0.01 <0.01

Johnson 1 Tyras 2 Csicsko3

Chee4

Beta-Blocking Drugs for PrevenUon of Supraventrlcular Tachyarrhythmlas (SVT) After Coronary Artery Bypass Grafting

TABLE IV

Patients with SVT

Study Salazar s Stephenson e Oka7 Mohrs Silverman 9 Abel 1° Ivey11

White12 Roffman 13

Pts. (n) 42 223 54 103 100 100 109 41 172

Drug (daily dose in mg) Prop (40) Prop (40) Prop (6 IV) Prop (20-40) Prop (40) Prop (80) Prop (80) Tim (20) Digoxin -I- Prop (60)

Time Started After operation (hrs) Immediately 18 Immediately 6 24 Immediately 24 3-7 24 48

Control Group 50% 18% 59-94% 40% 28% 38% 16% 100% 28%

Treated Group 25% 8% 26% 5-27% 6% 17% 13% 100% 2%

p Value <0.05 <0.05 <0.01 <0.01 <0.01 <0.05 NS -<0.005

IV -- intravenous; NS -- difference not significant; Prop -- propranolol; tim = timolol.

<0.001 vs control group). Among the 39 patients in the control group receiving fl-blocking drugs preoperatively, 18 (46%) had atrial arrhythmias. Only 2 of the 11 patients in the control group who did not receive flblocking drugs preoperatively had such arrhythmias. In the 3 patients who had supraventricular tachyarrhythmias during Holter monitoring, the arrhythmia had also been noted and recorded by the nurses caring for them. In most patients arrhythmias were terminated within a few hours with oral fl-blocking therapy, but 5 patients required cardioversion. In 1 patient only, acebutolol was discontinued because of a side effect (second-degree atrioventricular block after 5 days of treatment). The acebutolol dose at discharge ranged from 200 to 1,000 mg (average 635 4- 225).

Discussion Several studies have examined the incidence of supraventricular arrhythmias after CABG. 1-13 Reported frequencies range from 11% 2 to 94%, 7 but in a recent study 12in which long-term ECG recording for 7 consecutive days after surgery was performed, supraventricular arrhythmias were detected in all patients. However, most of those arrhythmias were not sustained and were likely to have little or no clinical consequences. Types of supraventricular arrhythmias reported vary from 1 study to another. We have not encountered paroxysmal supraventricular tachycardia in the present study, similar to studies by Stephenson,6 Silverman 9 and their co-workers, but this arrhythmia was the most frequent supraventricular tacchyarrhythmia in a study by White et al. ~2

Two categories of drugs have been advocated for prevention of supraventricular arrhythmias after CABG: digitalis and fl-blocking drugs. A few studies evaluating results of digitalis administration before and after CABG suggest beneficial effects of these drugs. However, Selzer et a117 cautioned against the routine use of digitalis in patients undergoing cardiac surgery, because of their increased myocardial sensitivity18 and thus increased danger of toxicity. Tyras et al 2 showed that prophylactic digitalis treatment yields no benefit in treatment of supraventricular tachyarrhythmias after CABG and may, in fact, predispose the patient to these arrhythmias (Table III). Beta-adrenoceptor blocking drugs, particularly propranolol, are effective in reducing the incidence of postoperative supraventricular tachyarrhythmias. There are several reasons to advocate use of these drugs after CABG. Usually, patients are receiving flblocking drugs before CABG and a "rebound effect" after withdrawal of these drugs can occur if the drugs are not resumed preoperativelyS,7,8,14; besides "surgery-related" causes, 19 and particularly the hyperadrenergic state seen in the postoperative period, this rebound effect has been implicated as a maj or cause of supraventricular arrhythmias. Oka et al 7 reported a high incidence {94%} of supraventricular tachyarrhythmias when propranolol therapy was discontinued 48 hours before operation {vs 26% when the drug was maintained until the operation and restarted immediately}. Several studies with various designs have shown the efficacy of propranolol prophylaxis, 5-1° using, as a

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ACEBUTOLOLFOR ATRIAL FIBRILLATION/FLUTTER

rule, a small dose of the drug (Table IV). However, a recent report from Ivey et a111 did not show any decrease in postoperative tachyarrhythmias in a propranolol-treated group. White et a112showed that prophylactic use of timolol decreased the frequency and severity of supraventricular tachyarrhythmias after CABG, although all patients in both treated and control groups had at least 1 bout of supraventricular tachyarrhythmias. Their monitoring period, however, began much earlier than ours. Acebutolol given orally during the first postoperative week, beginning at 36 hours after CABG, was extremely effective in preventing supraventricular tachyarrhythmias. Moreover, only I patient in the acebutolol-treated group had a side effect that required discontinuation of the drug. Patients with relative contraindications to fl-blocking drugs, such as low ejection fraction, were not included in this study and this may account for the very low rate of adverse effects observed. Thus, oral acebutolol is recommended as a standard therapeutic regimen in prevention of supraventricular tachyarrhythmias after CABG. Whether it provides any advantage over other available ~-blocking drugs remains to be determined.

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