Presentation on theme: "POST CABG ATRIAL FIBRILLATION/FLUTTER; IDENTIFICATION OF THE HIGH RISK PATIENTS AND THE EFFECTIVENESS OF PROPHYLACTIC BETA BLOCKER THERAPY IN A COMMUNITY."— Presentation transcript:
POST CABG ATRIAL FIBRILLATION/FLUTTER; IDENTIFICATION OF THE HIGH RISK PATIENTS AND THE EFFECTIVENESS OF PROPHYLACTIC BETA BLOCKER THERAPY IN A COMMUNITY HOSPITAL SETTING Muhammad Fahad Khan Muhammad Ali Khan
Background Atrial fibrillation (AF) is the most common complication of coronary artery bypass grafting (CABG) with or without valvular surgery. AF has been reported in up to 40 percent of patients in the post-operative period. Most cases of AF occur between 24 to 48 hours after the surgery. Maisel, WH, Rawn, JD, Stevenson, WG. Atrial fibrillation after cardiac surgery. Ann Intern Med 2001; 135:1061.Mathew, JP, Fontes, ML, Tudor, IC, et al. A multicenter risk index for atrial fibrillation after cardiac surgery. JAMA 2004; 291:1720.Villareal, RP, Hariharan, R, Liu, BC, et al. Postoperative atrial fibrillation and mortality after coronary artery bypass surgery. J Am Coll Cardiol 2004; 43:742.
AF contributes significantly to morbidity, cost and length of stay associated with this procedure. Postoperative AF may also identify a subset of patients with increased in-hospital and long-term mortality. A multicenter risk index for atrial fibrillation after cardiac surgery. JAMA 2004; 291:1720.Villareal, RP, Hariharan, R, Liu, BC, et al. Postoperative atrial fibrillation and mortality after coronary artery bypass surgery. J Am Coll Cardiol 2004; 43:742. Background
The ACC/AHA guidelines ACC/AHA strongly recommends prophylactic therapy for the prevention of post CABG AF especially for high risk patients. Recommend preoperative or postoperative oral BB (beta blocker) therapy for the prevention of post CABG AF (Class 1B). Other recommended pharmacological prophylactic therapies include Sotalol (Class 1C) and Amiodarone (Class 1C). ACC/AHA 2004 guideline update for coronary artery bypass graft surgery: summary article. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1999 Guidelines for Coronary
Purpose of Study To evaluate the predictability of this arrhythmia using previously identified risk factors. To assess the efficacy of recommended prophylactic therapy (beta blockers) in a community hospital setting.
Methodology This is a retrospective chart review study of consecutive patients undergoing CABG with or without valvular surgery during 1 year period at SBMH. The protocol was approved by SBMH IRB committee. Patient Consent was waived being a retrospective chart review study.
Definition Atrial fibrillation was defined as irregular QRS complex without identifiable P waves. All patients were monitored using 24 hour telemetery. Atrial fibrillation was diagnosed on the review of EKG and telemetry strips and confirmed with physician’s notes. Post operative period was defined as the time spent in the hospital after the surgery.
Inclusion Criteria All the patients who had CABG (off-pump or on- pump) with or with valvular surgery between 1/1/06 and 12/31/06 at SBMH were included in the study. All the patients who had valvular surgery alone between 1/1/06 and 12/31/06 at SBMH were also included.
Exclusion Criteria Patients who underwent open heart surgery other than CABG and valvular surgery. Patient who already had atrial fibrillation/flutter or other arrhythmia at the time they entered the surgery.
Methodology Patients who developed new onset AF for more than one hour in duration after the surgery were designated as cases and those who did not, as controls. We compared 67 different preoperative, intraoperative and postoperative variables between these two groups. These variables were derived from the previous studies with similar objectives.
Abbreviations used BB Beta Blocker NS BB Non Specific Beta Blocker AF Atrial Fibrillation MPL Metoprolol ATL Atenolol PPL Propranolol CRG Carvedilol ARR Absolute risk reduction RR Relative Risk RCT Randomized Control Trial LA Left Atrium PO Oral IV Intravenous HTN Hypertension T Total
Total patients 247 231 13 patients excluded Arrhythmia 3 patients isolated AVR/MVR 53 patients AF 178 patients No AF
Statistical Analysis Categorical variables were analyzed using Chi-square test. Whereas continuous variables were analyzed using independent sample t-test. Statistical significance was defined as p<0.05. All the statistical analysis was carried out using SPSS. (Chicago, Ill. version 17).
Statistical Analysis Multivariate analysis was carried out using Logistic regression model to find out independent correlation between different variables and the development of post CABG AF.
Results Total Patients = 231
Results Parameters Post-op AF n=53 (%) No Post-op AF n=178 (%) p-value Odds ratio (95% CI) Age, yrs (mean ± SD)72 ± 9.264 ± 11.5<0.001------- Male/Female36/17123/550.5------- *Abnormal BNP6 (11.3)6 (3.4)0.033.7 (1.1-11.9) Smoking25 (47.2)113 (63.5)0.030.5 (0.3-1) History of CHF7 (13.2)6 (3.4)0.0134.4 (1.4-13.6) History of AF15 (28.3)5 (2.8)<0.00113.6 (4.7-39.9) EF ≤ 40 %12 (22.6)24 (13.5)0.84-------- *Abnormal LA size19 (38.8) + 38 (23.5) + 0.032 (1-4) Pre-op Beta Blockers35 (66)87 (47.9)0.022 (1.1-3.9) Pre-op Digoxin3 (5.7)1 (0.6)0.0410.6 (1.1-104) Off pump CABG27(51)97(54)0.6491.15(0.62-2.1) Aortic clamp time (min) 72.8 ± 51.568.9 ± 30.50.42-------- Number of Anastomoses 3.3 ±1.23.7 ±1.10.1--------
Results 53 of 231 (23%) patients undergoing CABG with or without valvular surgery developed AF during post- operative period. Cases were older than controls (mean age 72 vs. 64, p< 0.01). On bivariate analysis, multiple factors were found to predispose to the development of AF.
Effectiveness of BB therapy In terms of prophylactic therapy, 35 of 53 (66%) cases were taking BB as compared to 87 of 178 (48%) of controls (p=0.02). But on multivariate analysis only Age (p=0.002) and BNP (p=0.019) were found to be independent predictors for the development of post CABG AF.
Effectiveness of BB therapy VariableOn BB(122)Not on BB(109)P value Age (mean)67.34 ± 10.664.3 ± 12.20.041 Abnormal BNP750.77 Abnormal EF16200.28 AF at disharge1360.23 Post op AF35180.029 AVR551 Statin91410.00 h/o AF1820.00 h/o CHF761 h/o/ CAD60350.008 h/o COPD11101 h/o DM46240.1 Dyslipidemia97630.00 HTN105640.00 Sex (male)78810.1
Conclusion We concluded that advanced age, history of AF, enlarged left atrial size, history of CHF and elevated BNP levels as predictors for the development of post CABG AF. In terms of prophylactic beta blocker therapy, 35 of 122 (28.6%) developed AF while on beta blocker whereas only 18 of 109 (16.5%) developed AF in the absence of prophylactic beta blockers. However, on multivariate analysis, this predisposing effect was not significant. Based on this analysis, BB did not show protection against post CABG AF.
Limitations Retrospective chart review analysis. The patient population is small. Belongs to a single community hospital thus the data and results derived may not be generalized to reflect other cardiac surgery centers.
Possible reasons for BB ineffectiveness Decreased oral bioavailability of these drugs during perioperative period ? Is there any difference among different class of BB ? IV BB better than oral BB?
Decreased Metoprolol bioavailability Valtola A, Kokki H, Gergov M, Ojanperä I, Ranta VP, Hakala T. Eur J Clin Pharmacol. 2007 May;63(5):471-8. Epub 2007 Feb 28.
Hypotheses If blood levels of oral MPL are lowest on first postoperative day, then it should create an effect similar to BB withdrawal. (BB withdrawal has been shown to predispose to the development of Post CABG AF). Prophylactic BB started on postoperative period should prevent AF better than preoperative BB due to lack of this withdrawal. As there will be no withdrawal due to IV BB, they should show better protection for post CABG AF. As pharmacokinetics varies among different BB, there should difference among different drugs as far as the prevention is concerned. Budeus M, Feindt P, Gams E, Wieneke H, Sack S, Erbel R, Perings C. Ann Thorac Surg. 2007 Jul;84(1):61-6.
Analysis We retrospectively reviewed 231 charts (same study population), to find out the timing, route and type of prophylactic BB. In our setting most of the patients were given Metoprolol. All the patients were given prophylactic BB orally. Major contraindications to BB included bronchospasm, hypotension and AV blocks.
Effectiveness of BB therapy Variable Postoperative BB (101) Preoperative BB (119) P value Age (mean) 64.0 ± 12.467.2 ± 10.70.05 Abnormal BNP 560.9 Abnormal EF 20150.14 AF disharge 5120.16 Post op AF 17330.05 AVR 550.8 Statin 36880.00 h/o CABG 040.00 h/o AF 2170.001 h/o CHF 660.77 h/o/ CAD 31580.006 h/o COPD 8110.7 h/o DM 23450.016 Dyslipidemia 58940.001 HTN 601010.00 Sex (male) 74760.13 Abnormal LA size 23330.27
Results There is statistically significant difference between two groups in terms of post CABG AF. But two groups are also different in terms of various variables like age, preoperative medications, h/o AF, CAD and DM. Partially proves the BB withdrawal hypothesis. Again limited retrospective study.
POOLED ANALYSIS We preferred pooled analysis over the meta-analysis to reveal even a smaller yet clinically significant difference. We searched the MEDLINE data base using the words, “BB”, “Post CABG arrhythmias”, “Prophylaxis of Post CABG AF”, “Randomized prospective trial”. We limited our search to 1990 till present due recent changes in the techniques and protocols of CABG. Initially 26 trials were selected but 7 were excluded due to various reasons.
Characteristics of the trials Trails were carefully reviewed by two independent reviewers with particular attention to inclusion criteria, method of randomization, exact timing of administration of postoperative BB, definition of atrial fibrillation, continuity of telemetry during postoperative period and the duration of follow up. In all trials, patients with low EF < 40%, severe COPD and AV blocks were excluded.
Initial trials selected 26 19 trials 3 trials non RCT Total patients 2011 AF patients 416 3 Trials NS BB Combination of BB used
Characteristics of the trials All the studies can be combined as they used similar patient inclusion/exclusion criteria, similar drug and control groups, similar definition of AF and a common primary end point i.e., the development of post CABG AF. Patient groups were not significantly different regarding various pre, intra and postoperative variables.
DrugsPostopPeropAF (post)AF (pre)ARRRRP value MPL(PO)963156247(25.6%)43(27.5%)2%0.930.61 MPL(IV)120-----20(16.66%)------10%0.640.031 MPL(T)1083156267(24.6%)43(27.5%)3%0.890.43 CRG(PO)115-----18(15.6%)------10%0.600.018 PPL(PO)109-----18(16.5%)------9%0.640.036 PPL(IV)123-----30(24.39%)------8% INC.1.460.137 PPL(T)232-----48(20.68%)------4%0.830.199 ATL(PO)19340(20.7%)7.5%0.750.136 Pooled analysis- Results DrugsPostopPeropAF (post)AF (pre)ARRRRP value MPL(PO)963156247(25.6%)43(27.5%)2%0.930.61 MPL(IV)120-----20(16.66%)------10%0.640.031 MPL(T)1083156267(24.6%)43(27.5%)3%0.890.43 CRG(PO)115-----18(15.6%)------10%0.600.018 PPL(PO)109-----18(16.5%)------9%0.640.036 PPL(IV)123-----30(24.39%)------8% INC. 1.460.137 PPL(T)232-----48(20.68%)------4%0.830.199 ATL(PO)19340(20.7%)7.5%0.750.136 P value calculated by chi-squire method. Pre op BB349 total 83 AF, Post op BB1419 total 283 AF, p value= 0.112 P value calculated by chi-squire method. Pre op BB349 total 83 AF, Post op BB1419 total 283 AF, p value= 0.112 P value calculated by chi-squire method. Pre op BB- 349 total, 83 AF. Post op BB1419 total 283 AF, p value= 0.112
Comparison of Metoprolol subgroups
Metoprolol and Carvedilol
Metoprolol and Propranolol
Results Total number of patients given BB for the prevention of AF, including pre and post operative period were 2011. Of these 416 (23.6%) developed new onset post CABG AF. 349 got BB in the preoperative period and 83 (23.78%) of them developed AF. All the preoperative BB were given orally. On other hand 1662 got postoperative BB for the prevention of AF. Of these patients 333 (20%) developed new onset AF. 1419 patients were given oral BB while 243 were given IV BB during the postoperative period. 283 (20%) of oral group while 50 (20.5%) of the IV group developed post CABG AF.
Recommendations and conclusion BB differ significantly among themselves for their ability to prevent post CABG AF. There is also significant difference between oral and IV forms as well as timing of administration. Our analysis partially explains why BB are not fully effective for the prevention of post CABG AF. In our opinion further randomized control trials need to be done to evaluate the timing, route of administration and the type of beta blockers to prevent post CABG AF.