Carvedilol compared with metoprolol on left ventricular ejection fraction after coronary artery bypass graft

on Left Ventricular Ejection Fraction After Mehran Shahzamani, MD, Arash Ghanavati, MD, Azam Nouri Froutagheh, RN, Mahnoosh Foroughi, MD, Hosein Rahimian, MD, Azadeh Shahsanaei, MD, Seyed Ahmad Hasantash, MD, Ali Dabbagh, MD A number of elective coronary artery bypass graft (CABG) surgerypatients have impaired underlying left ventricular function (poor ejec-tion fraction). This study was performed to compare the effect of postop-erative oral carvedilol versus metoprolol on left ventricular ejectionfraction (LVEF) after CABG compared with metoprolol. In a double-blind clinical trial, 60 patients with coronary artery disease, aged 35 to65 years, who had an ejection fraction of 15% to 35% were included.
Either carvedilol or metoprolol was administered the day after CABG.
The patients were evaluated by the same cardiologist 14 days beforeand 2 and 6 months after elective CABG. The results demonstrated betterimprovements in LVEF in the carvedilol group. No difference regardingpostoperative arrhythmias or mortality was detected. The results suggestthat carvedilol may exert more of an improved myocardial effect than me-toprolol for the low ejection fraction patients undergoing CABG in theearly postoperative months.
Keywords: carvedilol, metoprolol, coronary artery bypass graft surgery.
Ó 2011 by American Society of PeriAnesthesia Nurses A NUMBER OF elective coronary artery bypass do not improve left ventricular ejection fraction graft (CABG) surgery patients have impaired under- (LVEF) more than 10%.Repeated hospitalizations lying left ventricular function (poor ejection frac- are a frequent problem during the postoperative tion [EF])After CABG, these patients typically months, primarily because of preexisting heart Mehran Shahzamani, MD, Fellowship in Cardiac Surgery, kord, Iran; Seyed Ahmad Hasantash, MD, Fellowship in Assistant Professor, Department of Cardiac Surgery, Shahid Be- Cardiac Surgery, Professor, Department of Cardiac Surgery, heshti University of Medicine, Tehran, Iran; Arash Ghanavati, Shahid Beheshti University of Medicine, Tehran, Iran; and MD, Fellowship in Cardiac Surgery, Assistant Professor, Depart- Ali Dabbagh, MD, Fellowship in Cardiac Anesthesiology, Asso- ment of Cardiac Surgery, Shahid Beheshti University of Medi- ciate Professor, Anesthesiology Research Center and Anesthesi- cine, Tehran, Iran; Azam Nouri Froutagheh, RN, Research ology Department, Shahid Beheshti University of Medical Development Department, Modarres Hospital, Shahid Be- heshti University of Medical Sciences, Tehran, Iran; Mahnoosh Conflict of interest: None to report.
Foroughi, MD, Fellowship in Cardiac Surgery, Assistant Profes- Address correspondence to Ali Dabbagh, Anesthesiology Re- sor, Department of Cardiac Surgery, Shahid Beheshti Univer- search Center, Shahid Beheshti University of Medical Sciences, sity of Medical Sciences, Tehran, Iran; Hosein Rahimian, MD, Fellowship in Cardiac Surgery, Department of Cardiac Surgery, Ó 2011 by American Society of PeriAnesthesia Nurses Modarres Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Azadeh Shahsanaei, MD, Research Deputy, Shahrekord University of Medical Sciences, Shahre- Journal of PeriAnesthesia Nursing, Vol 26, No 6 (December), 2011: pp 384-387 failure. This preexisting heart failure leads to in-  evidence of atrioventricular block or severe creased postoperative mortality and morbidity sinoatrial node dysfunction, according to b-adrenergic blockers have been shown to decrease  any contraindications for administration of the mortality and morbidity of heart failure pa- tientCarvedilol, a nonselective third-generation The patients were assigned randomly into one of adrenergic blocker, is more effective than otherb two study groups using a computer table of ran- -adrenergic blocking agents, especially in patients dom numbers for random allocation. The first group (group 1), which included 30 patients, (MI)This study was designed and performed to received oral carvedilol, and the second group compare the effect of postoperative oral carvedilol (group 2), also including 30 patients, received versus oral metoprolol on increasing EF after CABG.
oral metoprolol tartrate. Both groups receivedthe drugs after elective CABG.
All the patients underwent echocardiography dur- This research study received approval from the ing 14 preoperative days before the surgical opera- Institutional Review Board Committee for Ethical tion and again at 2 and 6 months after CABG.
Considerations, Research Deputy, Shahid Beheshti The echocardiography examination was again University of Medical Sciences, Tehran, Iran.
performed by the same cardiologist and echocardio- The research project was accomplished during graphic machine (GE Vingmed Vivid 5 Echocardiog- a 24-month period from January 2008 through raphy System; All Imaging Systems, Inc., Irvine, CA) December 2009. Patients gave written informed in the same hospital. During the postoperative consent before enrollment in the study.
period, the patients were evaluated regarding atrialarrhythmias and 1-month mortality.
In a prospective randomized double-blind clinicaltrial, 60 patients with coronary artery disease Conventional on-pump CABG was performed in all were enrolled. The study included 22 women 60 patients. After establishing cardiopulmonary and 38 men, whose ages ranged from 35 to 65 bypass, mild hypothermia (32C, passive cooling) years and who had an EF of 15% to 35%. The EF was used, with crystalloid cardioplegia solution.
was confirmed by the same cardiologist during The b-blocker drugs were begun the day after the operation. Low-dose oral carvedilol (3.125 mg)twice daily was started for the first group. If the The patients also each had a history of recent MI.
patient tolerated the drug, the dose was gradually The MI had occurred more than 4 weeks before increased over 2 weeks to reach a maximum of the study and was documented by electrocardio- 12.5 mg twice daily. Low-dose oral metoprolol tar- graphic (ECG) and dipyridamole-thallium imaging trate (50 mg/day) was used for the second group results. Those patients who had a recent MI during by the same pattern of administration. If the pa- the last 4 weeks were excluded because those who tient tolerated the drug, the dose was gradually have had a recent MI within 4 weeks are not usu- increased over 2 weeks to reach a maximum ally considered appropriate candidates for elective of 200 mg twice daily to reach a maximum of CABG. Viability of the myocardium was deter- 400 mg per day. These doses are comparing equi- mined by single-photon emission computed to- potent dosages of the two drugs. For both drugs, mography (SPECT) and stress echocardiography.
the signs of intolerance that were critical markerswere intolerable fatigue, sinus bradycardia with Those patients older than 65 or younger than a heart rate of less than 45 per minute, and 35 years were excluded from the study. Also, the fol- shortness of breath. If any of these occurred with lowing items were considered as exclusion criteria: drug administration, the drug would be discontin- ued and the patient would be excluded from the  history of recent MI during the last 4 weeks study. Fortunately, none of the patients had any signs or symptoms of intolerance in any of the two There was only one death in the second group (me- toprolol group), which occurred in the fifth post-operative day after a cerebral vascular accident.
These medications were controlled to preventtheir effect on the myocardial function: digoxin, Both groups had increased performance of the left ventricle as demonstrated in their EF of the left diuretics. No other variables with a possibility for ventricle (LVEF), 2 and 6 months after CABG, affecting the myocardial function were considered when compared with their preoperative echocar- necessary to be controlled and monitored. This is diography assessments. In group 1 (ie, carvedilol), EF was increased from baseline values to higherranges in the assessments performed at 2- and 6-month periods. In group 2 (ie, metoprolol), theEF had a similar pattern. The improvements in The study data were recorded and extracted from LVEF were significantly increased in group 1 (car- each patient’s data sheet. Statistical analysis was vedilol group) compared with group 2 (metopro- performed using SPSS (version 11.5; SPSS Inc, Chicago, IL). For statistical data analysis, Student had no significant difference regarding functional t test, chi-square test, and analysis of variance status assessed by the New York Heart Association were used. A value for P less than .05 was consid- classification, 6 months after the operation.
Although bradycardia was more common in the carvedilol group (three patients versus one pa-tient), the incidence of other arrhythmias (atrial The two groups had no statistically significant dif- fibrillation [AF] or flutter, premature atrial beats, ference regarding age and the number of coronary or premature ventricular contractions) was not grafts in the operation (There were no dif- significantly different. No difference may have ferences between the two groups regarding gender or in the incidence of diabetes mellitus, hyperlipid-emia, hypertension, previous history of MI, smok- ing, and preoperative arrhythmias (P value for allthe variables greater than .05). The two groups The study demonstrated an increase in LVEF in carve- did not differ regarding their medications, includ- dilol group. The study suggests that carvedilol is ing digoxin, angiotensin-converting enzyme inhib- more effective in patients than metoprolol to in- crease EF after CABG. EF may rise 5% to 10% afterCABG surgery, however, in this study, the assess- The results also demonstrated that there was no ments performed after 6 months demonstrated that difference regarding lengths of surgery, pump the increase was greater than 10% in both groups.
run, intensive care unit stay, and hospitalization be- The carvedilol group increased approximately tween the two groups. All CABG operations were 18%. Much of this increase occurred during the first LVEF, left ventricular ejection fraction; CABG, coro- Figures are demonstrated as mean 6 standard Figures are demonstrated as mean 6 standard deviation.
2 months after CABG, and this increase continued postoperative period after landiolol administration.
Landiolol was not assessed in our study; but in otherstudies, landiolol has demonstrated an enhanced In a 2005 study that looked at LVEF after CABG in protective effect against tachycardia during AF in 20 patients with chronic hibernated myocardium post-CABG patientAnother study demonstrated studied before and after revascularization, the ef- that in post-CABG patients, therapeutic landiolol in fect of carvedilol on hibernating myocardium was ‘‘low doses’’ can decrease the prevalence of AF.
significantly better than that of metoprolol. The However, our study did not demonstrate any differ- authors of the study described their finding related ence regarding the incidence or prevalence of ‘‘partially’’ to the ‘‘reduced cardiomyocyte degener- arrhythmias or postoperative 6-month mortality.
ation’’ after carvedilol administration.All our These issues differed from previous research, but patients had a history of previous MI that was evi- the results of this study could demonstrate the denced by ECG, stress echocardiography, or SPECT, effect of carvedilol on LVEF to be superior to but the patients in the above study had hibernating metoprolol, a therapeutic effect of the drug that myocardium that would be accompanied with could be because of its effects as a counteradrener- a better response to revascularization, and the gic agenTherefore, it would demonstrate this sample size was smaller than that in our study.
effect as better performance on the poorlyfunctioning myocardium during the early post- Carvedilol was demonstrated to produce better effects on the performance of the LVEF thanmetoprolol (with equal doses), especially when prescribed long The difference in patientmortality after metoprolol and carvedilol adminis- Carvedilol could improve LVEF in the early postop- tration is due to the greater counteradrenergic erative period after CABG. When compared with properties of carvedilol. Both drugs are b-blocking metoprolol in patients with low EF, the patients agents, but it is only carvedilol that is both a nonse- demonstrate better early postoperative perfor- lective b-blocker and also an a-1 blockerTo mance of left ventricle. Evaluating patients with strengthen these findings, other studies have as- at least 1-year follow-up is recommended to assess sessed the effects of carvedilol when used in the the long-term outcome of such cases.
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