International Journal of Cardiology 177 (2014) 53–56
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Timing of coronary artery bypass graft surgery for acute myocardial infarction patients: A meta-analysis Hong-Lin Chen a, Kun Liu b,⁎ a b
Nantong University, Nantong City, PR China Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Nantong City, PR China
a r t i c l e
i n f o
Article history: Received 4 August 2014 Received in revised form 21 September 2014 Accepted 23 September 2014 Available online 2 October 2014 Keywords: Myocardial infarction Coronary artery bypass graft Early surgery Late surgery Meta-analysis
For acute myocardial infarction (MI) patients, early revascularization resulted in a 13.2% absolute and a 67% relative improvement in 6year survival compared with initial medical stabilization [1]. It was also found in elderly patients, with the in-hospital mortality relative risk of 0.46 (0.28 to 0.75) in patients aged ≥ 75 years and 0.76 (0.59 to 0.99) in patients aged b75 years [2]. Percutaneous coronary intervention (PCI) is always performed as a first choice for early revascularization. Coronary artery bypass grafting (CABG) is sometimes used for multi-vessel disease, lesions of the main trunk of the left coronary artery, and unsuccessful PCI. However, CABG soon after acute MI is associated with high operative mortality and morbidity. The reported early mortality rate of CABG for acute MI is between 3.6% and 42.9% [3,4]. It is still controversial what the best time to carry out CABG is. In this paper, we aim to conduct a meta-analysis to compare the postoperative mortality between early CABG surgery and late CABG surgery, and assess the optimal timing of coronary artery bypass grafting in acute myocardial infarction. We searched PubMed and ISI databases up to 30 July 2014. The search terms included myocardial infarction, coronary artery bypass graft, early surgery, late surgery, and time. We also supplemented our searches by manually reviewing the references of all relevant studies. The search was limited to English-language articles. To be in-
⁎ Corresponding author. E-mail address: [email protected] (K. Liu).
http://dx.doi.org/10.1016/j.ijcard.2014.09.127 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
cluded, studies had to meet the following criteria: (1) prospective and retrospective cohorts are all eligible; (2) compare clinical efficacy between early CABG surgery (b 1 day or b 2 day) and late CABG surgery (N 1 day or N 2 day) for acute MI, or compare clinical efficacy between different time intervals after acute MI to CABG surgery; (3) outcomes must included in-hospital mortality; and (4) provided odds ratio (OR) and 95% confidence interval (CI) between early CABG and late CABG, or provided OR between different CABG time intervals, or the ORs can be calculated from the raw data. We followed a standard protocol for data extraction. For each study, the following data were recorded: first author, year of publication, country, enroll year, study design, patient's number, type of MI (STsegment elevation myocardial infarction, STEMI and non-STEMI, NSTEMI), the in hospital death and survival patients' number in different time groups, the crude ORs and the adjusted ORs. The quality of articles was assessed according to the Newcastle–Ottawa Scale (NOS) [5]. Data extraction and article quality assessment were carried out independently by two reviewers. Disagreements were resolved by discussion together. We analyzed the data by the following processes: First, we assessed the in-hospital mortality difference between early CABG group and late CABG group. Fixed effect model or random effect model was chosen according to heterogeneity. Overall effects were determined using the Z test. Subgroup analysis was carried out in STEMI and NSTEMI subgroups. Visual inspection of a funnel plot, the Egger test, and Begg test were performed to assess publication bias. Sensitivity analyses were performed by only included prospective cohorts. Second, we examined the relationship between different CABG time intervals and in-hospital mortality of MI patients. Because adjusted ORs from the included articles have different reference standards, such as CABG with no MI, or CABG greater than 15 days after MI, we recalculated crude ORs based on the raw data. Dose–response meta-analysis proposed by Greenland and Longnecker [6] and Orsini et al. [7,8] was used for assessing the relationship. All statistical analyses were performed with Stata software, version 12.0 (Stata Corp, College Station, Texas). Two-sided P b 0.050 was considered statistically significant. We identified 12 studies with 100,048 patients for meta-analysis [3,4,9–18]. Among these, 7 were conducted in the United States, 2 in Germany, and Turkey, Spain, and India contributed a study, respectively. The studies included 4 prospective cohorts, and 8 retrospective cohorts. Three studies assessed STEMI, a study assessed NSTEMI, and 8 studies assessed STEMI/NSTEMI. The quality rating of the included
Study ID
OR (95% CI)
STEMI/ NSTEMI Assmann A, 2012 Weiss ES, 2008 Voisine P, 2006 Lee DC, 2001 Bana A, 1999 Lee JH, 1997 Braxton JH, 1995 Creswell LL, 1995 Subtotal (I-squared = 91.8%, p = 0.000)
4.17 (1.76, 9.88) 8.45 1.51 (1.24, 1.83) 11.56 5.18 (2.63, 10.22) 9.47 4.24 (3.56, 5.06) 11.60 13.88 (1.72, 111.86)3.55 12.50 (4.55, 34.33) 7.64 12.88 (2.33, 71.07) 4.62 2.05 (1.10, 3.84) 9.75 4.28 (2.38, 7.68) 66.64
% Weight
.
STEMI Filizcan U, 2011 Thielmann M, 2007 Lee DC, 2003 Subtotal (I-squared = 0.0%, p = 0.968)
4.56 (0.96, 21.61) 4.71 (1.22, 18.27) 5.30 (4.34, 6.47) 5.28 (4.34, 6.42)
5.15 5.97 11.54 22.66
0.96 (0.62, 1.48) 0.96 (0.62, 1.48)
10.70 10.70
3.76 (2.35, 6.02)
100.00
.
NSTEMI Parikh SV, 2010 Subtotal (I-squared = .%, p = .) .
Overall (I-squared = 92.6%, p = 0.000) NOTE: Weights are from random effects analysis .00894
1
112
Fig. 1. In-hospital mortality difference between early CABG group and late CABG group.
studies ranged from six to eight stars on the scale of nine. Table 1 showed the characteristics of the identified studies. All 12 studies with 100,048 patients were included in the analysis for in-hospital mortality difference between the early CABG group and late CABG group. The in-hospital mortality in the early CABG group ranged from 3.6% to 42.9%, and the mean in-hospital mortality was 7.7% (642/8293). In the late CABG group, the in-hospital mortality ranged from 1.8% to 7.1%, and the in-hospital mortality was 3.0% (2730/91,756). Table 1 also showed the in-hospital mortality between the early CABG group and late CABG group of the identified studies. There was substantial heterogeneity in the studies (I2 = 92.6%). The OR of in-hospital mortality between the two groups was 3.761 (95% CI 2.349 to 6.023; Z = 5.51, P = 0.000). In the STEMI subgroup, the OR was 5.276 (95% CI 4.339 to 6.416; Z = 16.67, P = 0.000); in the NSTEMI subgroup, the OR was 0.959 (95% CI 0.619 to 1.484; Z = 0.19, P = 0.850); and in the STEMI/NSTEMI subgroup, the OR was 4.279 (95% CI 2.385 to 7.676; Z = 4.87, P = 0.0.00). Fig. 1. showed the meta-analysis of in-hospital mortality difference between the early CABG group and late CABG group. The funnel plot was symmetrical (Fig. 2), and Begg's test (Z = 0.21, P = 0.837) and the Egger test (t = 0.38, P = 0.710) suggested no publication bias. Sensitivity
.4 .6 .8
se(logOR)
.2
0
Funnel plot with pseudo 95% confidence limits
1
2.8% 7.1% 3.8% 3.8% 3.9% 2.8% 3.0% 2.8% 1.8% 2.9% 5.5% 4.3% 1072 28 1753 4618 77 6942 30,269 41,722 111 270 103 2061 31 2 69 182 3 200 933 1202 2 8 6 92 10.8% 24.6% 3.6% 5.6% 15.5% 13.0% 14.0% 10.9% 20.0% 26.0% 42.9% 8.4% 58 43 795 4414 49 67 771 1284 8 27 4 131 7 14 30 262 9 10 126 157 2 10 3 12 STEMI/NSTEMI STEMI NSTEMI STEMI/NSTEMI STEMI STEMI/NSTEMI STEMI STEMI/NSTEMI STEMI/NSTEMI STEMI/NSTEMI STEMI/NSTEMI STEMI/NSTEMI 8 7 8 8 8 8 8 7 6 7 6 6 Germany Turkey USA USA Germany Spain USA USA India USA USA USA Assmann A, 2012 Filizcan U, 2011 Parikh SV, 2010 Weiss ES, 2008 Thielmann M, 2007 Voisine P, 2006 Lee DC, 2003 Lee DC, 2001 Bana A, 1999 Lee JH, 1997 Braxton JH, 1995 Creswell LL, 1995
2005–2009 2003–2008 2002–2008 1999–2005 2000–2007 1991–2005 1991–1996 1993–1996 1992–1997 1992–1995 1991–1992 1986–1993
Retrospective cohort Retrospective cohort Prospective cohort Retrospective cohort Prospective cohort Prospective cohort Retrospective cohort Retrospective cohort Retrospective cohort Prospective cohort Retrospective cohort Retrospective cohort
1168 85 2647 9476 138 7219 32,099 44,365 123 316 116 2296
Adjusted OR In hospital mortality In hospital survival Late CABG
In hospital death In hospital mortality In hospital survival In hospital death
Early CABG Type of MI
Patient number NOS Study design Enroll year Country First author, year
Table 1 Characteristics of the included studies assessing in-hospital mortality between early CABG group and late CABG group.
CABG: coronary artery bypass graft; MI: myocardial infarction; NOS: Newcastle–Ottawa Scale; OR: odds ratio; STEMI: ST segment elevation myocardial infarction; NSTEMI: non-ST segment elevation myocardial infarction; NR: not reported.
H.-L. Chen, K. Liu / International Journal of Cardiology 177 (2014) 53–56 NR NR 1.12 (0.71–1.78) 1.43 (1.12–1.18) NR NR NR NR NR NR NR NR
54
-1
0
1
2
3
logOR Fig. 2. The funnel plot for in-hospital mortality difference meta-analysis. The funnel plot was symmetrical which suggested no significant publication bias.
H.-L. Chen, K. Liu / International Journal of Cardiology 177 (2014) 53–56
Study
analyses by only included prospective cohorts showed that the result was robust, and the OR of in-hospital mortality between the two groups was 3.946 (95% CI 1.081 to 14.406; Z = 2.08, P = 0.038) (Fig. 3). Eleven studies with 87,491 patients were included in the analysis for in-hospital mortality between different CABG time intervals after acute MI. The in-hospital mortality ranged from 1.3% to 42.9% between different CABG time intervals, and the mean in-hospital mortality was 4.6% (4037/87,491). Table 2 showed the in-hospital mortality between different CABG time intervals after acute MI. Dose–response metaanalysis showed a statistically significant association between inhospital mortality and CABG time intervals after acute MI was observed (χ2 = 45.51, P = 0.000). In a linear model, the in-hospital mortality OR was 0.950 (95% CI 0.936–0.964) for every 1 day increase in CABG time intervals after acute MI, and 0.774 (95% CI 0.719–0.834) for every 5 day increase, 0.600 (95% CI 0.517–0.696), respectively. In a spline model, the OR of in-hospital mortality risk decreased alone with the CABG time intervals after acute MI, especially when time interval
%
ID
OR (95% CI)
Weight
Parikh SV, 2010
0.96 (0.62, 1.48)
27.59
Thielmann M, 2007
4.71 (1.22, 18.27) 21.71
Voisine P, 2006
5.18 (2.63, 10.22) 26.42
Lee JH, 1997
12.50 (4.55, 34.33) 24.28
Overall (I-squared = 91.1%, p = 0.000)
3.95 (1.08, 14.41) 100.00
NOTE: Weights are from random effects analysis
.0291
1
55
34.3
Fig. 3. Sensitivity analyses by only included prospective cohorts.
Table 2 Characteristics of the included studies assessing in-hospital mortality between different CABG time intervals after acute MI. First author, year
Assmann A, 2012
Filizcan U, 2011
Thielmann M, 2007
Voisine P, 2006
Lee DC, 2003
Lee DC, 2001 (transmural MI)
Lee DC, 2001 (non-transmural MI)
Bana A, 1999
Lee JH, 1997
Braxton JH, 1995
Creswell LL, 1995
Time to CABG (day)
In hospital death
In hospital survival
In hospital mortality
Crude OR [95% CI]
b0.25 0.25–1 2–3 4–10 11–20 21–30 b0.25 0.25–1 15–30 b0.25 0.25–1 2–3 4–7 8–14 b0.25 0.25–1 2–7 8–30 N31 b0.25 0.25–1 2–3 4–7 8–14 N15 b0.25 0.25–1 1–7 8–14 N15 b0.25 0.25–1 2–7 8–14 N15 b2 3–14 15–30 b1 1–7 8–24 b2 3–5 6–42 b0.25 0.25–2 3–14 15–42 N43
2 5 8 5 8 10 2 12 2 4 5 1 1 1 5 5 27 29 144 80 46 75 115 119 624 49 34 132 71 420 55 19 156 100 328 2 1 1 10 4 4 3 1 5 1 11 45 17 30
12 46 88 111 358 515 31 12 28 33 16 14 23 40 21 46 286 888 5768 484 287 871 2906 3999 22,493 356 216 2938 2887 15,734 423 287 4301 3604 11,820 8 35 76 27 121 149 4 12 91 10 121 824 244 993
14.8% 10.2% 8.8% 4.2% 2.3% 2.0% 6.1% 50.0% 7.1% 10.8% 23.8% 6.7% 4.2% 2.4% 19.2% 9.8% 8.6% 3.2% 2.4% 14.2% 13.8% 7.9% 3.8% 2.9% 2.7% 12.1% 13.6% 4.3% 2.4% 2.6% 11.5% 6.2% 3.5% 2.7% 2.7% 20.0% 2.8% 1.3% 26.0% 3.2% 2.6% 42.9% 7.7% 5.2% 9.1% 8.3% 5.2% 6.5% 2.9%
1 0.652 (0.092–7.702) 0.545 (0.093–5.093) 0.270 (0.039–3.175) 0.134 (0.023–1.446) 0.117 (0.021–1.220) 1 15.500 (2.693–154.091) 1.107 (0.075–16.195) 1 2.578 (0.474–14.642) 0.589 (0.011–6.755) 0.359 (0.007–3.997) 0.206 (0.004–2.257) 1 0.457 (0.095–2.239) 0.397 (0.131–1.459) 0.137 (0.046–0.501) 0.105 (0.038–0.361) 1 0.970 (0.641–1.456) 0.521 (0.368–0.738) 0.239 (0.175–0.328) 0.180 (0.132–0.246) 0.168 (0.130–0.218) 1 1.144 (0.692–1.872) 0.326 (0.229–0.472) 0.179 (0.120–0.267) 0.194 (0.141–0.271) 1 0.509 (0.279–0.894) 0.279 (0.200–0.393) 0.213 (0.150–0.307) 0.213 (0.157–0.294) 1 0.114 (0.002–2.608) 0.053 (0.001–1.193) 1 0.089 (0.019–0.345) 0.072 (0.016–0.279) 1 0.111 (0.002–2.075) 0.073 (0.010–0.670) 1 0.909 (0.109–42.987) 0.546 (0.075–24.216) 0.697 (0.089–31.987) 0.302 (0.041–13.541)
CABG: coronary artery bypass graft; MI: myocardial infarction; OR: odds ratio; NR: not reported.
Adjusted OR Adjusted OR [95% CI]
Compared with
3.2 (0.7–23.8) 4.9 (1.7–12.6) 3.8 (2.3–7.4) 1.6 (1.1–2.2) 1.4 (1.0–1.9) 1.0 (0.6–1.5) NR
CABG with no MI
0.8 (0.2–1.1) 1 3.4 (1.7–21.3) 0.5 (0.3–0.8) NR 3.92 (0.51–30.42) 5.08 (1.85–13.98) 4.33 (2.63–7.14) 1.50 (0.95–2.38) 1.18 (0.90–1.56) 1.609 (1.141–2.269) 1.965 (1.315–2.935) 1.529 (1.134–2.062) 1.032 (0.819–1.301) 0.939 (0.760–1.161) 1 1.774 (1.152–2.684) 2.671 (1.663–4.186) 1.184 (0.925–1.505) 0.812 (0.615–1.057) 1 1.909 (1.251–2.866) 1.314 (0.734–2.206) 1.131 (0.903–1.411) 0.866 (0.677–1.098) 1 NR
NR
CABG in 7–23 h after MI
CABG with no MI
CABG greater than 15 days after MI
CABG greater than 15 days after MI
CABG greater than 15 days after MI
NR
NR
NR
NR
NR
NR
NR
H.-L. Chen, K. Liu / International Journal of Cardiology 177 (2014) 53–56
Odds Ratio (for in-hospital mortality)
56
Linear Model Spline Model
1.000
0.500 0.250 0.125 0
5
10
15
20
25
30
35
40
45
50
CABG time after MI (day) Fig. 4. Dose–response meta-analysis of in-hospital mortality between different CABG time intervals after acute MI. The middle line is the point estimate of OR, and the lines on both sides are the 95% CI of OR.
is less than 10–15 days. Fig. 4. showed the result of dose–response meta-analysis of in-hospital mortality between different CABG time intervals after acute MI. Some limitations characterized our meta-analysis. First, substantial heterogeneity between the studies was found in the meta-analysis. Second, in-hospital mortality was used as the only one prognosis outcome. We didn't found long-term prognosis outcomes in the included studies. Third, we used crude ORs for dose–response meta-analysis. These limitations need to be considered when evaluating the conclusion. In conclusion, our meta-analysis indicated that early CABG after acute MI is more dangerous than late CABG, which leads to increase in-hospital mortality. We also found that in-hospital mortality risk decreased alone with the CABG time intervals after acute MI, especially when time interval is less than 10–15 days. We suggest that early CABG for acute MI should be avoided, especially in the first two weeks after acute MI. Conflict of interest The authors report no relationships that could be construed as a conflict of interest. References [1] Hochman JS, Sleeper LA, Webb JG, Dzavik V, Buller CE, Aylward P, et al. Early revascularization and long-term survival in cardiogenic shock complicating acute myocardial infarction. JAMA 2006;295(21):2511–5.
[2] Dzavik V, Sleeper LA, Cocke TP, Moscucci M, Saucedo J, Hosat S, et al. Early revascularization is associated with improved survival in elderly patients with acute myocardial infarction complicated by cardiogenic shock: a report from the SHOCK Trial Registry. Eur Heart J 2003;24(9):828–37. [3] Parikh SV, de Lemos JA, Jessen ME, Brilakis ES, Ohman EM, Chen AY, et al. Timing of in-hospital coronary artery bypass graft surgery for non-ST-segment elevation myocardial infarction patients results from the National Cardiovascular Data Registry ACTION Registry-GWTG (Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With The Guidelines). JACC Cardiovasc Interv 2010;3(4): 419–27. [4] Braxton JH, Hammond GL, Letsou GV, Franco KL, Kopf GS, Elefteriades JA, et al. Optimal timing of coronary artery bypass graft surgery after acute myocardial infarction. Circulation 1995;92(Suppl. 9):II66–8. [5] Wells GA, Shea B, O'Connell D, Peterson J, Welch V, Losos M, et al. The Newcastle– Ottawa Scale (NOS) for assessing the quality of non-randomized studies in metaanalysis. Ottawa Health Research Institute. Available from: URL: http://www.ohri. ca/programs/clinical_epidemiology/oxford.asp. [accessed 30 July, 2014]. [6] Greenland S, Longnecker MP. Methods for trend estimation from summarized dose– response data, with applications to meta-analysis. Am J Epidemiol 1992;135(11): 1301–9. [7] Orsini N, Bellocco R, Greenland S. Generalized least squares for trend estimation of summarized dose–response data. Stata J 2006;6:40–57. [8] Orsini N, Li R, Wolk A, Khudyakov P, Spiegelman D. Meta-analysis for linear and nonlinear dose–response relations: examples, an evaluation of approximations, and software. Am J Epidemiol 2012;175(1):66–73. [9] Assmann A, Boeken U, Akhyari P, Lichtenberg A. Appropriate timing of coronary artery bypass grafting after acute myocardial infarction. Thorac Cardiovasc Surg 2012; 60(7):446–51. [10] Filizcan U, Kurc E, Cetemen S, Soylu O, Aydogan H, Bayserke O, et al. Mortality predictors in ST-elevated myocardial infarction patients undergoing coronary artery bypass grafting. Angiology 2011;62(1):68–73. [11] Weiss ES, Chang DD, Joyce DL, Nwakanma LU, Yuh DD. Optimal timing of coronary artery bypass after acute myocardial infarction: a review of California discharge data. J Thorac Cardiovasc Surg 2008;135(3):503–11 [511.e1-3]. [12] Thielmann M, Neuhäuser M, Marr A, Herold U, Kamler M, Massoudy P, et al. Predictors and outcomes of coronary artery bypass grafting in ST elevation myocardial infarction. Ann Thorac Surg 2007;84(1):17–24. [13] Voisine P, Mathieu P, Doyle D, Perron J, Baillot R, Raymond G, et al. Influence of time elapsed b7etween myocardial infarction and coronary artery bypass grafting surgery on operative mortality. Eur J Cardiothorac Surg 2006;29(3):319–23. [14] Lee DC, Oz MC, Weinberg AD, Ting W. Appropriate timing of surgical intervention after transmural acute myocardial infarction. J Thorac Cardiovasc Surg 2003; 125(1):115–9 [discussion 119–20]. [15] Lee DC, Oz MC, Weinberg AD, Lin SX, Ting W. Optimal timing of revascularization: transmural versus nontransmural acute myocardial infarction. Ann Thorac Surg 2001;71(4):1197–202 [discussion 1202–4]. [16] Bana A, Yadava OP, Ghadiok R, Selot N. Myocardial revascularisation after acute myocardial infarction. Int J Cardiol 1999;69(2):209–16. [17] Lee JH, Murrell HK, Strony J, Cmolik B, Nair R, Lesnefsky E, et al. Risk analysis of coronary bypass surgery after acute myocardial infarction. Surgery 1997;122(4): 675–80 [discussion 680-1]. [18] Creswell LL, Moulton MJ, Cox JL, Rosenbloom M. Revascularization after acute myocardial infarction. Ann Thorac Surg 1995;60(1):19–26.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Timing of coronary artery bypass graft surgery for acute myocardial infarction patients: A meta-analysis Hong-Lin Chen a, Kun Liu b,⁎ a b
Nantong University, Nantong City, PR China Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Nantong City, PR China
a r t i c l e
i n f o
Article history: Received 4 August 2014 Received in revised form 21 September 2014 Accepted 23 September 2014 Available online 2 October 2014 Keywords: Myocardial infarction Coronary artery bypass graft Early surgery Late surgery Meta-analysis
For acute myocardial infarction (MI) patients, early revascularization resulted in a 13.2% absolute and a 67% relative improvement in 6year survival compared with initial medical stabilization [1]. It was also found in elderly patients, with the in-hospital mortality relative risk of 0.46 (0.28 to 0.75) in patients aged ≥ 75 years and 0.76 (0.59 to 0.99) in patients aged b75 years [2]. Percutaneous coronary intervention (PCI) is always performed as a first choice for early revascularization. Coronary artery bypass grafting (CABG) is sometimes used for multi-vessel disease, lesions of the main trunk of the left coronary artery, and unsuccessful PCI. However, CABG soon after acute MI is associated with high operative mortality and morbidity. The reported early mortality rate of CABG for acute MI is between 3.6% and 42.9% [3,4]. It is still controversial what the best time to carry out CABG is. In this paper, we aim to conduct a meta-analysis to compare the postoperative mortality between early CABG surgery and late CABG surgery, and assess the optimal timing of coronary artery bypass grafting in acute myocardial infarction. We searched PubMed and ISI databases up to 30 July 2014. The search terms included myocardial infarction, coronary artery bypass graft, early surgery, late surgery, and time. We also supplemented our searches by manually reviewing the references of all relevant studies. The search was limited to English-language articles. To be in-
⁎ Corresponding author. E-mail address: [email protected] (K. Liu).
http://dx.doi.org/10.1016/j.ijcard.2014.09.127 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
cluded, studies had to meet the following criteria: (1) prospective and retrospective cohorts are all eligible; (2) compare clinical efficacy between early CABG surgery (b 1 day or b 2 day) and late CABG surgery (N 1 day or N 2 day) for acute MI, or compare clinical efficacy between different time intervals after acute MI to CABG surgery; (3) outcomes must included in-hospital mortality; and (4) provided odds ratio (OR) and 95% confidence interval (CI) between early CABG and late CABG, or provided OR between different CABG time intervals, or the ORs can be calculated from the raw data. We followed a standard protocol for data extraction. For each study, the following data were recorded: first author, year of publication, country, enroll year, study design, patient's number, type of MI (STsegment elevation myocardial infarction, STEMI and non-STEMI, NSTEMI), the in hospital death and survival patients' number in different time groups, the crude ORs and the adjusted ORs. The quality of articles was assessed according to the Newcastle–Ottawa Scale (NOS) [5]. Data extraction and article quality assessment were carried out independently by two reviewers. Disagreements were resolved by discussion together. We analyzed the data by the following processes: First, we assessed the in-hospital mortality difference between early CABG group and late CABG group. Fixed effect model or random effect model was chosen according to heterogeneity. Overall effects were determined using the Z test. Subgroup analysis was carried out in STEMI and NSTEMI subgroups. Visual inspection of a funnel plot, the Egger test, and Begg test were performed to assess publication bias. Sensitivity analyses were performed by only included prospective cohorts. Second, we examined the relationship between different CABG time intervals and in-hospital mortality of MI patients. Because adjusted ORs from the included articles have different reference standards, such as CABG with no MI, or CABG greater than 15 days after MI, we recalculated crude ORs based on the raw data. Dose–response meta-analysis proposed by Greenland and Longnecker [6] and Orsini et al. [7,8] was used for assessing the relationship. All statistical analyses were performed with Stata software, version 12.0 (Stata Corp, College Station, Texas). Two-sided P b 0.050 was considered statistically significant. We identified 12 studies with 100,048 patients for meta-analysis [3,4,9–18]. Among these, 7 were conducted in the United States, 2 in Germany, and Turkey, Spain, and India contributed a study, respectively. The studies included 4 prospective cohorts, and 8 retrospective cohorts. Three studies assessed STEMI, a study assessed NSTEMI, and 8 studies assessed STEMI/NSTEMI. The quality rating of the included
Study ID
OR (95% CI)
STEMI/ NSTEMI Assmann A, 2012 Weiss ES, 2008 Voisine P, 2006 Lee DC, 2001 Bana A, 1999 Lee JH, 1997 Braxton JH, 1995 Creswell LL, 1995 Subtotal (I-squared = 91.8%, p = 0.000)
4.17 (1.76, 9.88) 8.45 1.51 (1.24, 1.83) 11.56 5.18 (2.63, 10.22) 9.47 4.24 (3.56, 5.06) 11.60 13.88 (1.72, 111.86)3.55 12.50 (4.55, 34.33) 7.64 12.88 (2.33, 71.07) 4.62 2.05 (1.10, 3.84) 9.75 4.28 (2.38, 7.68) 66.64
% Weight
.
STEMI Filizcan U, 2011 Thielmann M, 2007 Lee DC, 2003 Subtotal (I-squared = 0.0%, p = 0.968)
4.56 (0.96, 21.61) 4.71 (1.22, 18.27) 5.30 (4.34, 6.47) 5.28 (4.34, 6.42)
5.15 5.97 11.54 22.66
0.96 (0.62, 1.48) 0.96 (0.62, 1.48)
10.70 10.70
3.76 (2.35, 6.02)
100.00
.
NSTEMI Parikh SV, 2010 Subtotal (I-squared = .%, p = .) .
Overall (I-squared = 92.6%, p = 0.000) NOTE: Weights are from random effects analysis .00894
1
112
Fig. 1. In-hospital mortality difference between early CABG group and late CABG group.
studies ranged from six to eight stars on the scale of nine. Table 1 showed the characteristics of the identified studies. All 12 studies with 100,048 patients were included in the analysis for in-hospital mortality difference between the early CABG group and late CABG group. The in-hospital mortality in the early CABG group ranged from 3.6% to 42.9%, and the mean in-hospital mortality was 7.7% (642/8293). In the late CABG group, the in-hospital mortality ranged from 1.8% to 7.1%, and the in-hospital mortality was 3.0% (2730/91,756). Table 1 also showed the in-hospital mortality between the early CABG group and late CABG group of the identified studies. There was substantial heterogeneity in the studies (I2 = 92.6%). The OR of in-hospital mortality between the two groups was 3.761 (95% CI 2.349 to 6.023; Z = 5.51, P = 0.000). In the STEMI subgroup, the OR was 5.276 (95% CI 4.339 to 6.416; Z = 16.67, P = 0.000); in the NSTEMI subgroup, the OR was 0.959 (95% CI 0.619 to 1.484; Z = 0.19, P = 0.850); and in the STEMI/NSTEMI subgroup, the OR was 4.279 (95% CI 2.385 to 7.676; Z = 4.87, P = 0.0.00). Fig. 1. showed the meta-analysis of in-hospital mortality difference between the early CABG group and late CABG group. The funnel plot was symmetrical (Fig. 2), and Begg's test (Z = 0.21, P = 0.837) and the Egger test (t = 0.38, P = 0.710) suggested no publication bias. Sensitivity
.4 .6 .8
se(logOR)
.2
0
Funnel plot with pseudo 95% confidence limits
1
2.8% 7.1% 3.8% 3.8% 3.9% 2.8% 3.0% 2.8% 1.8% 2.9% 5.5% 4.3% 1072 28 1753 4618 77 6942 30,269 41,722 111 270 103 2061 31 2 69 182 3 200 933 1202 2 8 6 92 10.8% 24.6% 3.6% 5.6% 15.5% 13.0% 14.0% 10.9% 20.0% 26.0% 42.9% 8.4% 58 43 795 4414 49 67 771 1284 8 27 4 131 7 14 30 262 9 10 126 157 2 10 3 12 STEMI/NSTEMI STEMI NSTEMI STEMI/NSTEMI STEMI STEMI/NSTEMI STEMI STEMI/NSTEMI STEMI/NSTEMI STEMI/NSTEMI STEMI/NSTEMI STEMI/NSTEMI 8 7 8 8 8 8 8 7 6 7 6 6 Germany Turkey USA USA Germany Spain USA USA India USA USA USA Assmann A, 2012 Filizcan U, 2011 Parikh SV, 2010 Weiss ES, 2008 Thielmann M, 2007 Voisine P, 2006 Lee DC, 2003 Lee DC, 2001 Bana A, 1999 Lee JH, 1997 Braxton JH, 1995 Creswell LL, 1995
2005–2009 2003–2008 2002–2008 1999–2005 2000–2007 1991–2005 1991–1996 1993–1996 1992–1997 1992–1995 1991–1992 1986–1993
Retrospective cohort Retrospective cohort Prospective cohort Retrospective cohort Prospective cohort Prospective cohort Retrospective cohort Retrospective cohort Retrospective cohort Prospective cohort Retrospective cohort Retrospective cohort
1168 85 2647 9476 138 7219 32,099 44,365 123 316 116 2296
Adjusted OR In hospital mortality In hospital survival Late CABG
In hospital death In hospital mortality In hospital survival In hospital death
Early CABG Type of MI
Patient number NOS Study design Enroll year Country First author, year
Table 1 Characteristics of the included studies assessing in-hospital mortality between early CABG group and late CABG group.
CABG: coronary artery bypass graft; MI: myocardial infarction; NOS: Newcastle–Ottawa Scale; OR: odds ratio; STEMI: ST segment elevation myocardial infarction; NSTEMI: non-ST segment elevation myocardial infarction; NR: not reported.
H.-L. Chen, K. Liu / International Journal of Cardiology 177 (2014) 53–56 NR NR 1.12 (0.71–1.78) 1.43 (1.12–1.18) NR NR NR NR NR NR NR NR
54
-1
0
1
2
3
logOR Fig. 2. The funnel plot for in-hospital mortality difference meta-analysis. The funnel plot was symmetrical which suggested no significant publication bias.
H.-L. Chen, K. Liu / International Journal of Cardiology 177 (2014) 53–56
Study
analyses by only included prospective cohorts showed that the result was robust, and the OR of in-hospital mortality between the two groups was 3.946 (95% CI 1.081 to 14.406; Z = 2.08, P = 0.038) (Fig. 3). Eleven studies with 87,491 patients were included in the analysis for in-hospital mortality between different CABG time intervals after acute MI. The in-hospital mortality ranged from 1.3% to 42.9% between different CABG time intervals, and the mean in-hospital mortality was 4.6% (4037/87,491). Table 2 showed the in-hospital mortality between different CABG time intervals after acute MI. Dose–response metaanalysis showed a statistically significant association between inhospital mortality and CABG time intervals after acute MI was observed (χ2 = 45.51, P = 0.000). In a linear model, the in-hospital mortality OR was 0.950 (95% CI 0.936–0.964) for every 1 day increase in CABG time intervals after acute MI, and 0.774 (95% CI 0.719–0.834) for every 5 day increase, 0.600 (95% CI 0.517–0.696), respectively. In a spline model, the OR of in-hospital mortality risk decreased alone with the CABG time intervals after acute MI, especially when time interval
%
ID
OR (95% CI)
Weight
Parikh SV, 2010
0.96 (0.62, 1.48)
27.59
Thielmann M, 2007
4.71 (1.22, 18.27) 21.71
Voisine P, 2006
5.18 (2.63, 10.22) 26.42
Lee JH, 1997
12.50 (4.55, 34.33) 24.28
Overall (I-squared = 91.1%, p = 0.000)
3.95 (1.08, 14.41) 100.00
NOTE: Weights are from random effects analysis
.0291
1
55
34.3
Fig. 3. Sensitivity analyses by only included prospective cohorts.
Table 2 Characteristics of the included studies assessing in-hospital mortality between different CABG time intervals after acute MI. First author, year
Assmann A, 2012
Filizcan U, 2011
Thielmann M, 2007
Voisine P, 2006
Lee DC, 2003
Lee DC, 2001 (transmural MI)
Lee DC, 2001 (non-transmural MI)
Bana A, 1999
Lee JH, 1997
Braxton JH, 1995
Creswell LL, 1995
Time to CABG (day)
In hospital death
In hospital survival
In hospital mortality
Crude OR [95% CI]
b0.25 0.25–1 2–3 4–10 11–20 21–30 b0.25 0.25–1 15–30 b0.25 0.25–1 2–3 4–7 8–14 b0.25 0.25–1 2–7 8–30 N31 b0.25 0.25–1 2–3 4–7 8–14 N15 b0.25 0.25–1 1–7 8–14 N15 b0.25 0.25–1 2–7 8–14 N15 b2 3–14 15–30 b1 1–7 8–24 b2 3–5 6–42 b0.25 0.25–2 3–14 15–42 N43
2 5 8 5 8 10 2 12 2 4 5 1 1 1 5 5 27 29 144 80 46 75 115 119 624 49 34 132 71 420 55 19 156 100 328 2 1 1 10 4 4 3 1 5 1 11 45 17 30
12 46 88 111 358 515 31 12 28 33 16 14 23 40 21 46 286 888 5768 484 287 871 2906 3999 22,493 356 216 2938 2887 15,734 423 287 4301 3604 11,820 8 35 76 27 121 149 4 12 91 10 121 824 244 993
14.8% 10.2% 8.8% 4.2% 2.3% 2.0% 6.1% 50.0% 7.1% 10.8% 23.8% 6.7% 4.2% 2.4% 19.2% 9.8% 8.6% 3.2% 2.4% 14.2% 13.8% 7.9% 3.8% 2.9% 2.7% 12.1% 13.6% 4.3% 2.4% 2.6% 11.5% 6.2% 3.5% 2.7% 2.7% 20.0% 2.8% 1.3% 26.0% 3.2% 2.6% 42.9% 7.7% 5.2% 9.1% 8.3% 5.2% 6.5% 2.9%
1 0.652 (0.092–7.702) 0.545 (0.093–5.093) 0.270 (0.039–3.175) 0.134 (0.023–1.446) 0.117 (0.021–1.220) 1 15.500 (2.693–154.091) 1.107 (0.075–16.195) 1 2.578 (0.474–14.642) 0.589 (0.011–6.755) 0.359 (0.007–3.997) 0.206 (0.004–2.257) 1 0.457 (0.095–2.239) 0.397 (0.131–1.459) 0.137 (0.046–0.501) 0.105 (0.038–0.361) 1 0.970 (0.641–1.456) 0.521 (0.368–0.738) 0.239 (0.175–0.328) 0.180 (0.132–0.246) 0.168 (0.130–0.218) 1 1.144 (0.692–1.872) 0.326 (0.229–0.472) 0.179 (0.120–0.267) 0.194 (0.141–0.271) 1 0.509 (0.279–0.894) 0.279 (0.200–0.393) 0.213 (0.150–0.307) 0.213 (0.157–0.294) 1 0.114 (0.002–2.608) 0.053 (0.001–1.193) 1 0.089 (0.019–0.345) 0.072 (0.016–0.279) 1 0.111 (0.002–2.075) 0.073 (0.010–0.670) 1 0.909 (0.109–42.987) 0.546 (0.075–24.216) 0.697 (0.089–31.987) 0.302 (0.041–13.541)
CABG: coronary artery bypass graft; MI: myocardial infarction; OR: odds ratio; NR: not reported.
Adjusted OR Adjusted OR [95% CI]
Compared with
3.2 (0.7–23.8) 4.9 (1.7–12.6) 3.8 (2.3–7.4) 1.6 (1.1–2.2) 1.4 (1.0–1.9) 1.0 (0.6–1.5) NR
CABG with no MI
0.8 (0.2–1.1) 1 3.4 (1.7–21.3) 0.5 (0.3–0.8) NR 3.92 (0.51–30.42) 5.08 (1.85–13.98) 4.33 (2.63–7.14) 1.50 (0.95–2.38) 1.18 (0.90–1.56) 1.609 (1.141–2.269) 1.965 (1.315–2.935) 1.529 (1.134–2.062) 1.032 (0.819–1.301) 0.939 (0.760–1.161) 1 1.774 (1.152–2.684) 2.671 (1.663–4.186) 1.184 (0.925–1.505) 0.812 (0.615–1.057) 1 1.909 (1.251–2.866) 1.314 (0.734–2.206) 1.131 (0.903–1.411) 0.866 (0.677–1.098) 1 NR
NR
CABG in 7–23 h after MI
CABG with no MI
CABG greater than 15 days after MI
CABG greater than 15 days after MI
CABG greater than 15 days after MI
NR
NR
NR
NR
NR
NR
NR
H.-L. Chen, K. Liu / International Journal of Cardiology 177 (2014) 53–56
Odds Ratio (for in-hospital mortality)
56
Linear Model Spline Model
1.000
0.500 0.250 0.125 0
5
10
15
20
25
30
35
40
45
50
CABG time after MI (day) Fig. 4. Dose–response meta-analysis of in-hospital mortality between different CABG time intervals after acute MI. The middle line is the point estimate of OR, and the lines on both sides are the 95% CI of OR.
is less than 10–15 days. Fig. 4. showed the result of dose–response meta-analysis of in-hospital mortality between different CABG time intervals after acute MI. Some limitations characterized our meta-analysis. First, substantial heterogeneity between the studies was found in the meta-analysis. Second, in-hospital mortality was used as the only one prognosis outcome. We didn't found long-term prognosis outcomes in the included studies. Third, we used crude ORs for dose–response meta-analysis. These limitations need to be considered when evaluating the conclusion. In conclusion, our meta-analysis indicated that early CABG after acute MI is more dangerous than late CABG, which leads to increase in-hospital mortality. We also found that in-hospital mortality risk decreased alone with the CABG time intervals after acute MI, especially when time interval is less than 10–15 days. We suggest that early CABG for acute MI should be avoided, especially in the first two weeks after acute MI. Conflict of interest The authors report no relationships that could be construed as a conflict of interest. References [1] Hochman JS, Sleeper LA, Webb JG, Dzavik V, Buller CE, Aylward P, et al. Early revascularization and long-term survival in cardiogenic shock complicating acute myocardial infarction. JAMA 2006;295(21):2511–5.
[2] Dzavik V, Sleeper LA, Cocke TP, Moscucci M, Saucedo J, Hosat S, et al. Early revascularization is associated with improved survival in elderly patients with acute myocardial infarction complicated by cardiogenic shock: a report from the SHOCK Trial Registry. Eur Heart J 2003;24(9):828–37. [3] Parikh SV, de Lemos JA, Jessen ME, Brilakis ES, Ohman EM, Chen AY, et al. Timing of in-hospital coronary artery bypass graft surgery for non-ST-segment elevation myocardial infarction patients results from the National Cardiovascular Data Registry ACTION Registry-GWTG (Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With The Guidelines). JACC Cardiovasc Interv 2010;3(4): 419–27. [4] Braxton JH, Hammond GL, Letsou GV, Franco KL, Kopf GS, Elefteriades JA, et al. Optimal timing of coronary artery bypass graft surgery after acute myocardial infarction. Circulation 1995;92(Suppl. 9):II66–8. [5] Wells GA, Shea B, O'Connell D, Peterson J, Welch V, Losos M, et al. The Newcastle– Ottawa Scale (NOS) for assessing the quality of non-randomized studies in metaanalysis. Ottawa Health Research Institute. Available from: URL: http://www.ohri. ca/programs/clinical_epidemiology/oxford.asp. [accessed 30 July, 2014]. [6] Greenland S, Longnecker MP. Methods for trend estimation from summarized dose– response data, with applications to meta-analysis. Am J Epidemiol 1992;135(11): 1301–9. [7] Orsini N, Bellocco R, Greenland S. Generalized least squares for trend estimation of summarized dose–response data. Stata J 2006;6:40–57. [8] Orsini N, Li R, Wolk A, Khudyakov P, Spiegelman D. Meta-analysis for linear and nonlinear dose–response relations: examples, an evaluation of approximations, and software. Am J Epidemiol 2012;175(1):66–73. [9] Assmann A, Boeken U, Akhyari P, Lichtenberg A. Appropriate timing of coronary artery bypass grafting after acute myocardial infarction. Thorac Cardiovasc Surg 2012; 60(7):446–51. [10] Filizcan U, Kurc E, Cetemen S, Soylu O, Aydogan H, Bayserke O, et al. Mortality predictors in ST-elevated myocardial infarction patients undergoing coronary artery bypass grafting. Angiology 2011;62(1):68–73. [11] Weiss ES, Chang DD, Joyce DL, Nwakanma LU, Yuh DD. Optimal timing of coronary artery bypass after acute myocardial infarction: a review of California discharge data. J Thorac Cardiovasc Surg 2008;135(3):503–11 [511.e1-3]. [12] Thielmann M, Neuhäuser M, Marr A, Herold U, Kamler M, Massoudy P, et al. Predictors and outcomes of coronary artery bypass grafting in ST elevation myocardial infarction. Ann Thorac Surg 2007;84(1):17–24. [13] Voisine P, Mathieu P, Doyle D, Perron J, Baillot R, Raymond G, et al. Influence of time elapsed b7etween myocardial infarction and coronary artery bypass grafting surgery on operative mortality. Eur J Cardiothorac Surg 2006;29(3):319–23. [14] Lee DC, Oz MC, Weinberg AD, Ting W. Appropriate timing of surgical intervention after transmural acute myocardial infarction. J Thorac Cardiovasc Surg 2003; 125(1):115–9 [discussion 119–20]. [15] Lee DC, Oz MC, Weinberg AD, Lin SX, Ting W. Optimal timing of revascularization: transmural versus nontransmural acute myocardial infarction. Ann Thorac Surg 2001;71(4):1197–202 [discussion 1202–4]. [16] Bana A, Yadava OP, Ghadiok R, Selot N. Myocardial revascularisation after acute myocardial infarction. Int J Cardiol 1999;69(2):209–16. [17] Lee JH, Murrell HK, Strony J, Cmolik B, Nair R, Lesnefsky E, et al. Risk analysis of coronary bypass surgery after acute myocardial infarction. Surgery 1997;122(4): 675–80 [discussion 680-1]. [18] Creswell LL, Moulton MJ, Cox JL, Rosenbloom M. Revascularization after acute myocardial infarction. Ann Thorac Surg 1995;60(1):19–26.
