Johan D. Aasbo, DO; Andrew T. Lawrence, MD; Kousik Krishnan, MD; Michael H. Kim, MD; Richard G. Trohman, MD
Potential Financial Conflicts of Interest: Consultancies: M.H. Kim, R.G. Trohman (Guidant CRM Business Strategy Advisory Board); Honoraria: M.H. Kim, R.G. Trohman (St. Jude Medical, Inc., Guidant CRM); Grants received: M.H. Kim, R.G. Trohman (St. Jude Medical, Inc., Medtronic, Inc., Guidant CRM, Wyeth-Ayerst).
Requests for Single Reprints: Richard G. Trohman, MD, Rush University Medical Center, 1750 West Harrison, Suite 983 Jelke, Chicago, IL 60612; e-mail, email@example.com.
Current Author Addresses: Dr. Aasbo: Medical College of Wisconsin, Division of Cardiovascular Medicine, 9200 West Wisconsin Avenue, Suite 5100, Milwaukee, WI 53226.
Drs. Lawrence, Krishnan, and Trohman: Rush University Medical Center, 1750 West Harrison, Suite 983 Jelke, Chicago, IL 60612.
Dr. Kim: Health Partners, Inc., 640 Jackson Street, Mail Stop 11102M, St. Paul, MN 55101.
Author Contributions: Conception and design: J.D. Aasbo, R.G. Trohman.
Analysis and interpretation of the data: J.D. Aasbo, A.T. Lawrence, R.G. Trohman.
Drafting of the article: J.D. Aasbo, K. Krishnan, M.H. Kim, R.G. Trohman.
Critical revision of the article for important intellectual content: J.D. Aasbo, R.G. Trohman.
Final approval of the article: J.D. Aasbo, A.T. Lawrence, K. Krishnan, M.H. Kim, R.G. Trohman.
Statistical expertise: J.D. Aasbo.
Administrative, technical, or logistic support: J.D. Aasbo.
Collection and assembly of data: J.D. Aasbo, A.T. Lawrence.
Aasbo J., Lawrence A., Krishnan K., Kim M., Trohman R.; Amiodarone Prophylaxis Reduces Major Cardiovascular Morbidity and Length of Stay after Cardiac Surgery: A Meta-Analysis. Ann Intern Med. 2005;143:327-336. doi: 10.7326/0003-4819-143-5-200509060-00008
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Published: Ann Intern Med. 2005;143(5):327-336.
Tachyarrhythmias are common after heart surgery and are associated with increased morbidity.
This meta-analysis of 10 randomized, double-blind trials involving 1744 patients undergoing open-heart surgery found that, compared with placebo, amiodarone reduced atrial and ventricular arrhythmias, stroke, and length of hospital stay. Side effects included nausea and bradycardia that was not always deemed clinically important.
Trial participants did not always receive prophylaxis with β-blockers. Dosages and timing of amiodarone and length of follow-up varied across studies.
Atrial fibrillation and atrial flutter are common after cardiac surgery. Studies have estimated their incidence to be as high as 40% to 60% after coronary artery bypass grafting or cardiac valve surgery (1, 2). These arrhythmias most often develop between the second and fifth postoperative day (3), with a peak incidence in the first 2 to 3 days (4). Atrial fibrillation and atrial flutter increase the occurrence of postoperative stroke (4), perioperative myocardial infarction, heart failure, and readmission to the intensive care unit (and reintubation) (5); length of stay; and total cost of hospitalization (6, 7). Recent data suggest that atrial fibrillation and atrial flutter are independent risk factors for inpatient and long-term mortality after open-heart surgery (8).
Michael E Craycraft
JFK Medical Center
September 8, 2005
To the Editor:
I read with great interest the recent article in the Annals by Aasbo et al.(1). The topic of prophylaxis for prevention of atrial fibrillation in cardiac surgery patients has been of recent interest in our institution. However, the 10 studies included in the meta-analysis do not appear to be unique. The study included by White et al(2) appears to be from the the same data represented in the study by Giri et al.(3). It appears that the same study was published twice in two seperate journals. Both studies appear to involve the same 220 patients from Hartford Hospital from 1998-1999. I believe further investigation is warranted.
Respectfully, Michael E. Craycraft RPh JFK Medical Center Atlantis, FL
(1) Aasbo JD, Lawrence AT, Krishnan K et al. Amiodarone prophylaxis reduces major cardiovascular morbidity and length of stay after cardiac surgery: A meta-analysis. Ann Intern Med 2005;143:327-336.
(2) White CM, Giri S, Tsikouris, et al. A comparison of two amiodarone regimens to placebo in open heart surgery patients. Ann Thorac Surg. 2002;74:69-74.
(3) Giri S, White CM, Dunn AB, et al. Oral amiodarone for prevention of atrial fibrillation after open heart surgery, the Atrial Fibrillation Suppression Trial (AFIST): a randomized placebo-controlled trail. Lancet 2001; 357:830-836.
Sean P. Javaheri
Brooke Army Medical Center
September 12, 2005
Post cardiotomy atrial fibrillation: Where do we go from here?
We read with interest the excellent meta-analysis of amiodarone prophylaxis for cardiac surgery by Aasbo and colleagues.(1) Their analysis showed that amiodarone reduced major cardiovascular morbidity and length of stay when compared to placebo. However, as the authors note, a possible additive effect of amiodarone on a background of beta blocker therapy was not examined. In the Atrial Fibrillation Suppression Trail (2), oral amiodarone when combined with beta-blockers reduced the risk of post cardiotomy atrial fibrillation (absolute risk reduction 15.5%). However, while the adjusted relative risk of post cardiotomy atrial fibrillation in the subset of patients not receiving beta-blockers was significantly reduced in this trial, it did not reach statistical significance in the group that was taking both beta blockers and amiodarone. The Atrial Fibrillation Supression Trial II investigators were able to demonstrate a 9.3% absolute risk reduction in post cardiotomy atrial fibrillation with amiodarone.(3) Unfortunately, there was no data comparing the patients who were receiving only beta blockers to beta blockers and amiodarone. How beneficial are beta blockers alone? Prophylactic beta blockers reduce the incidence of post cardiotomy atrial fibrillation with a number needed to treat of only seven patients to prevent one episode.(4) This forms the basis for the ACC/AHA Atrial Fibrillation and Coronary Artery Bypass Guidelines (5,6) recommendation and the recent American College of Chest Physicians recommendation (7) that give beta blockers a class I recommendation for the prevention of post cardiotomy atrial fibrillation. These same recommendations suggest amiodarone should only be used when beta blockers are contraindicated. In a prior meta-analysis, beta-blockers, sotalol, and amiodarone all reduced the risk of post cardiotomy atrial fibrillation with no marked difference between them.(8) Given the lack of demonstrated superiority of amiodarone over beta blockers, one must consider the greater potential for adverse effects with amiodarone. In addition to the widely known complications of amiodarone therapy, we have recently been concerned about the association of phlebitis with intravenous of amiodarone. Supporting our clinical concern are reports of thrombophlebitis associated with intravenous amiodarone dating back to 1982 with rates up to 16%.(9,10,11) While thrombophlebitis has not been routinely reported in studies of amiodarone use on surgical services, it was noted to be one of the most frequent adverse effects in a trial of amiodarone use for cardioversion of recent onset atrial fibrillation.(12) Since thrombophlebitis can lead to infectious complications, increase hospital stays and attendant costs, and create discomfort for the patient, it is an important source of morbidity that must be taken into consideration when proposing intravenous amiodarone use. In summary, while the metaanalysis by Aasbo and colleagues(1) provides valuable evidence that amiodarone is more effective than placebo in the prevention of post cardiotomy atrial fibrillation, the more pressing question of how to further reduce this complication on a background of beta blocker therapy remains unanswered. We are curious to know what the current practice at the author's institution is regarding the role of amiodarone in the prevention of post cardiotomy atrial fibrillation. We agree with the authors that further large scale trials will be required to address the role of amiodarone in addition to beta blockers in the prevention of post cardiotomy atrial fibrillation.
Sean P. Javaheri, DO Eric A. Shry, MD James Furgerson, MD Sheri Y. Boyd, MD Brooke Army Medical Center Department of Cardiology San Antonio, TX 78234
1. Aasbo JD, Lawrence AT, Kirshnan K. et al. Amiodarone Prophylaxis Reduces Major Cardiovascular Morbidity and Length of Stay after Cardiac Surgery: A Meta-Analysis. Annals of Internal Medicine. 2005.143(5):327-336
2. Giri S, White CM, Dunn, AB et al. Oral Amiodarone for the Prevention of Atrial Fibrillation After Open Heart Surgery, The Atrial Fibrillation Suppression Trial (AFIST): A Randomised Placebo-Controlled Trial. Lancet. 2001;357:830-836.
3. White CM, Caron, MF, Kalus JS et al. Intravenous plus oral amiodarone, atrial septal pacing, or both strategies to prevent post- cardiothoracic surgery atrial fibrillation: the Atrial Fibrillation Suppression Trial II (AFIST II). Circulation. 2003;108(Suppl 1):200-206.
4. Omorphos S, Hanif, M, Dunning, J. Are prophylactic ÃŸ-blockers of benefit in reducing the incidence of AF following coronary bypass surgery? Interactive Cardiovascular and Thoracic Surgery. 2004;3:641-646.
5. Fuster V, Ryden LE, Asinger RW, Cannom DS, Crijns HJ, Frye RL, et al. ACC/AHA/ESC Guidelines for the Management of Patients With Atrial Fibrillation: Executive Summary. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines and Policy Conferences (Committee to Develop Guidelines for the Management of Patients With Atrial Fibrillation) Developed in Collaboration With the North American Society of Pacing and Electrophysiology. American College of Cardiology/American Heart Association Task Force on Practice Guidelines. European Society of Cardiology Committee for Practice Guidelines and Policy Conferences (Committee to Develop Guidelines for the Management of Patients With Atrial Fibrillation). North American Society of Pacing and Electrophysiology. Circulation. 2001;104:2118-50.
6. Eagle KA, Guyton RA, Davidoff R, Edwards FH. ACC/AHA Guideline Update for Coronary Artery Bypass Grafting. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines(Committee to Update the 1999 Guideline for Coronary Artery Bypass Grafting). Developed in Collaboration with American Association for Thoracic Surgery and Society of Thoracic Surgeons. Journal of the American College of Cardiology. 2004;44:1146 - 1154.
7. Bradley D, Creswell LL, Hogue CW, et al. Pharmacologic Prophylaxis: American College of Chest Physicians Guidelines for the Prevention and Management of Postoperative Atrial Fibrillation After Cardiac Surgery. Chest. 2005;128:S39-47
8. Crystal E, Connolly SJ, Sleik K, Ginger TJ, Yusuf S. Interventions on prevention of postoperative atrial fibrillation in patients undergoing heart surgery: a meta-analysis. Circulation.2002;106:75-80.
9. Aravanis C. Acute thrombophlebitis due to IV use of amiodarone. Chest 1982;82:515-6.
10. Hilleman DE, Spinler SA. Conversion of recent-onset atrial fibrillation with intravenous amiodarone: a meta-analysis of randomized controlled trials. Pharmacotherapy 2002;22:66-74.
11. Vardas PE, Kochiadakis GE, Igoumenidis NE, Tsatsakis AM, Simantirakis EN, Chlouverakis GI. Amiodarone as a first-choice drug for restoring sinus rhythm in patients with atrial fibrillation: a randomized, controlled study. Chest 2000;117:1538-1545.
12. Drug information by: http://www.rxlist.com/
Johan D. Aasbo
Medical College of Wisconsin
December 16, 2005
To the Editor,
We agree with Mr. Craycraft's observation that the studies by Giri et al. (1) and White et al. (2) included in our meta-analysis (3) presented similar cohort data. The number of stroke endpoints (16 in Giri, 9 in White), the percentage of the cohorts receiving B-blockers (72.4 % in Giri vs. 89.1 % in White) and the percentage of the cohorts having valvular surgery (26.9 % in Giri vs. 18.2 % in White) are different in the two papers. Although identified by the Annals of Thoracic Surgery as an "Original Article", in retrospect, it appeared likely (to us) that White et al. reported a substudy (rather than a duplicate) of AFIST. We spoke directly to Dr. White on 12/14/05. He confirmed that the Annals of Thoracic Surgery article was a substudy of AFIST and that the same patient population was used.
We regret the inadvertent inclusion of duplicate cohort data in our meta-analysis. In order to assess the impact of including the patient data twice, we performed a meta-analysis excluding the latter of these two publications (Ann Thorac Surg. 2002;74(1):69-74). The summary effects of the nine remaining trials are presented below:
incidence of atrial fibrillation or flutter (relative risk, 0.65 [95% CI, 0.55 to 0.77], p < 0.00001, I2 = 0%), incidence of atrial fibrillation or flutter in cohorts administering the drug preoperatively (relative risk, 0.63 [95% CI, 0.48 to 0.84], p = 0.001, I2 = 0%), incidence of atrial fibrillation or flutter in cohorts administering the drug perioperatively (relative risk, 0.65 [95% CI, 0.53 to 0.81], p < 0.0001, I2 = 5.6 %), incidence of atrial fibrillation or flutter in cohorts administering the drug orally (relative risk, 0.63 [95% CI, 0.48 to 0.84], p = 0.001, I2 = 0%), incidence of atrial fibrillation or flutter in cohorts administering the drug intravenously (relative risk, 0.67 [95% CI, 0.51 to 0.88], p = 0.003, I2 = 7.7 %), incidence of ventricular tachycardia and fibrillation (relative risk, 0.44 [CI, 0.29 to 0.67], p = 0.0001, I2 = 0%), incidence of stroke (relative risk, 0.44 [CI, 0.21 to 0.91], p = 0.03, I2 = 0%), and length of stay (weighted mean difference, - 0.7 days [CI, -1.18 to -0.22 days], p = 0.005, I2 = 22%).
Excluding the data from White and associates does not substantially alter the results of our meta-analysis. Our conclusion that amiodarone prophylaxis significantly reduces atrial fibrillation, major cardiovascular morbidity and length of hospital stay after cardiac surgery remains firm.
Johan D. Aasbo, D.O. Medical College of Wisconsin Milwaukee, WI 53226
Richard G. Trohman, M.D. Rush University Medical Center Chicago, IL 60612 Richard_Trohman@rush.edu
1. Giri S, White CM, Dunn AB, et al. Oral amiodarone for prevention of atrial fibrillation after open heart surgery, the Atrial Fibrillation Suppression Trial (AFIST): a randomised placebo-controlled trial. Lancet. 2001;357(9259):830-6.
2. White CM, Giri S, Tsikouris JP, et al. A comparison of two individual amiodarone regimens to placebo in open heart surgery patients. Ann Thorac Surg. 2002;74(1):69-74.
3. Aasbo JD, Lawrence AT, Krishnan K, Kim MH, Trohman RG. Amiodarone prophylaxis reduces major cardiovascular morbidity and length of stay after cardiac surgery: a meta-analysis. Ann Intern Med. 2005;143(5):327- 36.
September 16, 2010
Postoperative sinus tachycardia is a symptom- whether due to anxiety, SIRS, sepsis, fever,pain, hypotension, bleeding, hypoxia,.... The cause of this symptom should be sought. Prophylactic use of this drug as we dont know the occurrence of heart block,bradycardia, hypotension consequences after its use and also because it masqued the basic cause is not reasonable. As we dont prophylactically prescribed antifever, antibiotics, and many other drugs.
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