Transcript PREVENTION OF ATRIALFIBRILLATION/FLUTTER AFTER CABG …

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.
Background
 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.
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
 NS BB
 AF
 MPL
 ATL
 PPL
 CRG
Beta Blocker
Non Specific
Beta Blocker
Atrial
Fibrillation
Metoprolol
Atenolol
Propranolol
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
3 patients isolated
AVR/MVR
13 patients excluded
Arrhythmia
231
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
Post CABG AF
Total Patients = 231
53
178
AF
No AF
Results
Post-op AF
n=53 (%)
No Post-op
AF
n=178 (%)
p-value
Odds ratio
(95% CI)
72 ± 9.2
64 ± 11.5
<0.001
-------
Male/Female
36/17
123/55
0.5
-------
*Abnormal BNP
6 (11.3)
6 (3.4)
0.03
3.7 (1.1-11.9)
Smoking
25 (47.2)
113 (63.5)
0.03
0.5 (0.3-1)
History of CHF
7 (13.2)
6 (3.4)
0.013
4.4 (1.4-13.6)
History of AF
15 (28.3)
5 (2.8)
<0.001
13.6 (4.7-39.9)
EF ≤ 40 %
12 (22.6)
24 (13.5)
0.84
--------
19 (38.8)+
38 (23.5)+
0.03
2 (1-4)
Pre-op Beta Blockers
35 (66)
87 (47.9)
0.02
2 (1.1-3.9)
Pre-op Digoxin
3 (5.7)
1 (0.6)
0.04
10.6 (1.1-104)
Off pump CABG
27(51)
97(54)
0.649
1.15(0.62-2.1)
72.8 ± 51.5
68.9 ± 30.5
0.42
--------
3.3 ±1.2
3.7 ±1.1
0.1
--------
Parameters
Age, yrs (mean ± SD)
*Abnormal LA size
Aortic clamp time
(min)
Number of
Anastomoses
Results
 53 of 231 (23%) patients undergoing CABG with or
without valvular surgery developed AF during postoperative 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
Variable
On BB(122)
Not on BB(109)
P value
Age (mean)
67.34 ± 10.6
64.3 ± 12.2
0.041
Abnormal BNP
7
5
0.77
Abnormal EF
16
20
0.28
AF at disharge
13
6
0.23
Post op AF
35
18
0.029
AVR
5
5
1
Statin
91
41
0.00
h/o AF
18
2
0.00
h/o CHF
7
6
1
h/o/ CAD
60
35
0.008
h/o COPD
11
10
1
h/o DM
46
24
0.1
Dyslipidemia
97
63
0.00
HTN
105
64
0.00
Sex (male)
78
81
0.1
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 ± 12.4
67.2 ± 10.7
0.05
Abnormal BNP
5
6
0.9
Abnormal EF
20
15
0.14
AF disharge
5
12
0.16
Post op AF
17
33
0.05
AVR
5
5
0.8
Statin
36
88
0.00
h/o CABG
0
4
0.00
h/o AF
2
17
0.001
h/o CHF
6
6
0.77
h/o/ CAD
31
58
0.006
h/o COPD
8
11
0.7
h/o DM
23
45
0.016
Dyslipidemia
58
94
0.001
HTN
60
101
0.00
Sex (male)
74
76
0.13
Abnormal LA size
23
33
0.27
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
3 Trials NS BB
3 trials non RCT
19 trials
Total patients
2011
Combination of BB
used
AF patients
416
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.
Pooled analysis- Results
Drugs
Postop
Perop
AF (post)
AF (pre)
ARR
RR
P value
MPL(PO)
963
156
247(25.6%)
43(27.5%)
2%
0.93
0.61
MPL(IV)
120
-----
20(16.66%)
------
10%
0.64
0.031
MPL(T)
1083
156
267(24.6%)
43(27.5%)
3%
0.89
0.43
CRG(PO)
115
-----
18(15.6%)
------
10%
0.60
0.018
PPL(PO)
109
-----
18(16.5%)
------
9%
0.64
0.036
PPL(IV)
123
-----
30(24.39%)
------
8%
INC.
1.46
0.137
PPL(T)
232
-----
48(20.68%)
------
4%
0.83
0.199
40(20.7%)
7.5%
0.75
0.136
ATL(PO)
193
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
120
100
80
T
60
AF
40
20
0
MPL PO(preop)
MPL PO(postop)
MPL IV(postop)
Metoprolol and Carvedilol
120
100
80
T
60
AF
40
20
0
MPL PO(postop)
CRG PO(postop)
Metoprolol and Propranolol
120
100
80
T
60
AF
40
20
0
MPL PO(postop)
PPL PO(postop)
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.

THANK YOU