Aspirin remains the gold standard antiplatelet regimen following coronary artery bypass grafting (CABG), however, there is growing support for dual antiplatelet therapy (DAPT). This study compares outcomes of aspirin monotherapy versus DAPT following CABG. This was a propensity-matched retrospective study from a large, multi-hospital healthcare system. It included patients who received either aspirin monotherapy or DAPT following isolated CABG between 2011 and 2018. Patients prescribed aspirin monotherapy were started on 81 mg aspirin daily, and patients on DAPT were prescribed 81 mg aspirin daily and 75 mg clopidogrel daily. Patients received alternative drug dosing or antiplatelet agents other than clopidogrel only if this was prescribed for another diagnosis or they had a preexisting contraindication. Primary outcomes included overall survival and major adverse cardiac and cerebrovascular events (MACCE), defined as a composite of death, myocardial infarction, stroke, or repeat revascularization. Kaplan-Meier analysis and the log-rank test were used to compare survival and cumulative incidence curves and Gray’s test were used to compare MACCE. A total of 3,562 propensity-matched patients were included, 1,242 (34.9%) receiving aspirin monotherapy and 2,320 (65.1%) receiving DAPT. Groups were well-matched with respect to age, baseline comorbidity, indication for CABG, and completeness of revascularization. Median follow-up was 4.90 years (IQR 3.30 to 6.90 years). DAPT was associated with higher rate of postoperative transfusion (30.7% vs 25.4%, p = 0.001). Overall survival was comparable between groups (1-year aspirin 95.9% versus DAPT 97.2% and 5-years aspirin 86.3% versus DAPT 87.8%; log-rank p = 0.194). Rates of MACCE were also similar (1-year aspirin 9.4% versus DAPT 8.7% and 5-years aspirin 26.7% versus DAPT 24.7%; p = 0.798). In this propensity-matched analysis, DAPT did not confer any advantage in terms of improved survival or freedom from MACCE compared to aspirin monotherapy following isolated CABG, and was associated with a higher postoperative transfusion rate.
Aspirin has been the first line antiplatelet therapy for patients following coronary artery bypass grafting (CABG) to prevent graft occlusion and adverse cardiac events. , However, prior studies have suggested that clopidogrel as a monotherapy may be superior to aspirin alone in prevention of major adverse cardiac and cerebrovascular events (MACCE). Furthermore, treatment with dual antiplatelet therapy (DAPT) with aspirin and another antiplatelet agent has continued to gain popularity. Several studies have supported the use of DAPT post-CABG due to reduced incidence of MACCE and/or decreased native disease formation or graft occlusion. Conversely, other trials have reported no differences in these outcomes with DAPT over aspirin monotherapy in terms of MACCE or graft patency. Because the literature remains conflicted, postoperative antiplatelet therapy often remains at the discretion of the individual surgeon or practice. These practices can vary considerably, even within individual health institutions. This study compared outcomes of postoperative DAPT versus aspirin monotherapy in isolated CABG.
Methods
This study was a propensity-matched retrospective analysis from a single academic institution comprised of multiple hospitals in a regional healthcare system. It included adults (18 years or older) that underwent primary isolated CABG between January 2011 and June 2018. Patients that underwent redo cardiac surgery or concomitant procedures were excluded. Patients were then stratified based on antiplatelet regimen at time of discharge: aspirin monotherapy versus DAPT consisting of aspirin in addition to another antiplatelet agent. Patients that received other forms of systemic anticoagulation or had a contraindication to anticoagulation and/or antiplatelet therapy were excluded. Patients not surviving to discharge from the index hospitalization were also excluded from long-term analysis. This study was approved by the Institutional Review Board at the University of Pittsburgh.
In our institution, patients on aspirin monotherapy are started on 81 mg of aspirin daily. If a DAPT regimen is used, this consists of 81 mg daily and 75 mg clopidogrel daily. Patients only receive alternative dosages of medications or alternative antiplatelet agents in lieu of clopidogrel if they were previously prescribed prior to CABG, or have a contraindication. Antiplatelet agents are started on the first postoperative day unless concern for postoperative bleeding or thrombocytopenia exist. Actual chest tube drainage or platelet count cutoffs for withholding antiplatelet therapy in the immediate postoperative setting were surgeon dependent. Long-term post-CABG antiplatelet and/or anticoagulation regimens were analyzed by compiling active medication lists for each patient at the 3 months, 6 months, 1 year, and 5 years timepoints from the time of surgical revascularization.
Primary outcomes included overall survival and rates of MACCE. MACCE was defined as a composite endpoint of death, myocardial infarction, stroke, or need for repeat revascularization. Secondary outcomes included freedom from hospital readmission, postoperative blood transfusion requirements, and postoperative complications. Exploratory analysis was performed to investigate location of post-CABG myocardial infarction and associated bypass grafting to the affected region. For these events, location of infarction was determined by presenting electrocardiogram pattern, new wall motion abnormality on echocardiography, and/or intervenable lesion on coronary catheterization. Additionally, all available post-CABG computed tomography angiography studies were assessed to assess bypass graft patency.
Continuous data are presented as mean ± standard deviation for Gaussian variables or median [interquartile range (IQR)] for non-gaussian variables and all categorical data as number (percentage). Normality was assessed using the Kolmogorov-Smirnov test. Normally distributed continuous data and categorical data were compared with Pearson’s Chi-squared test or Fisher’s exact test when 25% of available data points had expected values <5. Non-Gaussian distributions were evaluated using Mann-Whitney U test.
Propensity score matching on a 1:2 basis was performed using nearest neighbor matching without replacement and caliper setting of 0.2 of the standard deviation of the logit propensity score. Patients were matched base on all preoperative demographics, comorbidities, cardiac presentation, operation status, as well as preoperative usage of antiplatelets, anticoagulation, and/or intravenous inotropes. Additionally, patients were matched based on number of diseased coronary vessels, usage of bilateral internal mammary artery harvest, usage of cardiopulmonary bypass, and completeness of revascularization following CABG. A standardized mean differences <10% between cohorts was considered adequately matched for each characteristic. This resulted in 3,562 cases, 1,242 receiving aspirin monotherapy and 2,320 receiving DAPT. Kaplan-Meier curves were created and compared using the log-rank test for overall survival. Cumulative incidence function curves were generated for MACCE and the Gray’s test was used to compare these curves.
Results
A total of 5,482 patients were included in this study, 1,246 (22.7%) who received aspirin monotherapy and 4,236 (77.3%) who received DAPT following CABG. In the non-matched cohorts, median age was 66 years, and patients had similar mean body mass index, body surface area, and had similar distributions of gender and race. The DAPT cohort had a higher prevalence of diabetes mellitus and chronic obstructive pulmonary disease. The most common presentation for CABG in both groups was NSTEMI, and number of diseased coronary vessels was similar. Median Society of Thoracic Surgeons risk for mortality was higher in the DAPT cohort. There was a higher utilization of cardiopulmonary bypass in the aspirin monotherapy group (89.1% vs 65.9%; p <0.001), with shorter median perfusion (89 minutes [IQR 73-111] versus 99 minutes [IQR 78 to 120], p <0.001) shorter cross-clamp times (59 minutes [IQR 46 to 75] versus 71 minutes [IQR 55 to 90], p <0.001), and with less frequent usage of bilateral internal mammary artery (IMA) grafting (20.0% vs 30.7%, p <0.001). Completeness of revascularization was higher in the DAPT group (83.6% vs 80.1%, p = 0.004). 61.2% of patients receiving aspirin monotherapy underwent CABG at Hospital 3 while 58.6% of patients receiving DAPT underwent CABG at Hospital 5 ( Table 1 ). Long-term postdischarge antiplatelet and anticoagulation regimens are presented in Table 2 .
| Variable | Aspirin (n = 1246) | DAPT (n = 4236) | p | Standardized mean difference |
|---|---|---|---|---|
| Age (years) | 66.00 (59.00-73.00) | 65.00 (58.00-73.00) | 0.103 | 0.06 |
| Body mass index (kg/m 2 ) | 29.33 (25.93-33.40) | 29.38 (25.97-33.30) | 0.728 | 0.01 |
| Body surface area (m 2 ) | 2.06 ± 0.27 | 2.05 ± 0.25 | 0.680 | 0.01 |
| Women | 300 (24.08%) | 1077 (25.42%) | 0.335 | 0.03 |
| White | 1179 (94.62%) | 3887 (91.76%) | 0.001 | 0.12 |
| Black | 38 (3.05%) | 234 (5.52%) | ||
| Other | 29 (2.33%) | 115 (2.71%) | ||
| Diabetes mellitus | 524 (42.05%) | 1952 (46.08%) | 0.012 | 0.08 |
| Dialysis dependency | 24 (1.93%) | 93 (2.20%) | 0.563 | 0.02 |
| Chronic obstructive pulmonary disease | 197 (15.81%) | 907 (21.41%) | 0.000 | 0.14 |
| Hypertension | 1096 (87.96%) | 3718 (87.77%) | 0.857 | 0.01 |
| Immunosuppression | 54 (4.33%) | 176 (4.15%) | 0.782 | 0.01 |
| Family history of CAD | 300 (24.08%) | 1172 (27.67%) | 0.012 | 0.08 |
| Cerebrovascular disease | 241 (19.34%) | 886 (20.92%) | 0.227 | 0.04 |
| Peripheral vascular disease | 176 (14.13%) | 881 (20.80%) | 0.000 | 0.18 |
| Prior cerebrovascular accident | 75 (6.02%) | 302 (7.13%) | 0.174 | 0.04 |
| Previous myocardial infarction | 766 (61.48%) | 2678 (63.22%) | 0.263 | 0.04 |
| Cardiac presentation | ||||
| Asymptomatic | 123 (9.87%) | 395 (9.32%) | 0.007 | 0.02 |
| Symptoms unlikely to be ischemia | 1 (0.08%) | 32 (0.76%) | ||
| Stable angina pectoris | 121 (9.71%) | 490 (11.57%) | ||
| Unstable angina pectoris | 489 (39.25%) | 1768 (41.74%) | ||
| NSTEMI | 393 (31.54%) | 1150 (27.15%) | ||
| STEMI | 78 (6.26%) | 278 (6.56%) | ||
| Symptoms equivalent to angina pectoris | 15 (1.20%) | 44 (1.04%) | ||
| Other | 26 (2.09%) | 79 (1.86%) | ||
| Congestive heart failure | 137 (11.00%) | 542 (12.80%) | 0.090 | 0.06 |
| NYHA symptoms | ||||
| 1 | 1115 (89.49%) | 3695 (87.23%) | 0.140 | 0.07 |
| 2 | 32 (2.57%) | 113 (2.67%) | ||
| 3 | 53 (4.25%) | 241 (5.69%) | ||
| 4 | 46 (3.69%) | 187 (4.41%) | ||
| Cardiac arrhythmia | 134 (10.75%) | 422 (9.96%) | 0.416 | 0.03 |
| Number of coronary coronary arteries | ||||
| 0 | 2 (0.16%) | 14 (0.33%) | 0.212 | 0.06 |
| 1 | 43 (3.45%) | 198 (4.67%) | ||
| 2 | 261 (20.95%) | 859 (20.28%) | ||
| 3 | 940 (75.44%) | 3165 (74.72%) | ||
| Intravenous inotropes | 17 (1.36%) | 53 (1.25%) | 0.754 | 0.01 |
| Cardiopulmonary bypass utilization | 1110 (89.09%) | 2793 (65.93%) | <0.001 | 0.58 |
| Perfusion time (minutes) | 89.00 (73.00-111.0) | 99.00 (78.00-120.0) | <0.001 | 0.21 |
| Cross-clamp time (minutes) | 59.00 (46.00-75.00) | 71.00 (55.00-90.00) | <0.001 | 0.47 |
| Intra-aortic balloon pump | ||||
| None | 1118 (89.73%) | 3930 (92.78%) | 0.001 | 0.13 |
| Preoperative | 112 (8.99%) | 246 (5.81%) | ||
| Intraoperative | 15 (1.20%) | 53 (1.25%) | ||
| Postoperative | 1 (0.08%) | 7 (0.17%) | ||
| Bilateral IMA harvest | 249 (19.98%) | 1300 (30.69%) | <0.001 | 0.25 |
| Serum creatinine (mg/dL) | 0.94 (0.79- 1.12) | 1.00 (0.80- 1.20) | <0.001 | 0.04 |
| Serum total albumin (g/dL) | 3.60 (3.30- 3.80) | 3.60 (3.40- 3.90) | <0.001 | 0.19 |
| Total bilirubin (mg/dL) | 0.50 (0.40- 0.70) | 0.60 (0.40- 0.80) | <0.001 | 0.21 |
| Left ventricular EF (%) | 55.00 (43.00-60.00) | 55.00 (45.00-58.00) | 0.066 | 0.04 |
| Operative status | ||||
| Elective | 458 (36.76%) | 1413 (33.36%) | 0.018 | 0.07 |
| Urgent | 743 (59.63%) | 2609 (61.59%) | ||
| Emergent | 45 (3.61%) | 214 (5.05%) | ||
| STS Mortality Risk | 0.99 (0.55- 2.06) | 1.08 (0.58- 2.22) | 0.021 | 0.04 |
| International normalized ratio (INR) | 1.00 (1.00- 1.10) | 1.10 (1.00- 1.10) | <0.001 | 0.09 |
| Complete revascularization | 998 (80.10%) | 3541 (83.59%) | 0.004 | 0.09 |
| Hospital number | ||||
| 1 | 144 (11.56%) | 846 (19.97%) | <0.001 | 0.23 |
| 2 | 65 (5.22%) | 176 (4.12%) | ||
| 3 | 762 (61.16%) | 278 (6.56%) | ||
| 4 | 63 (5.06%) | 456 (10.76%) | ||
| 5 | 212 (17.01%) | 2480 (58.55%) |
| Variable | 3 months | 6 months | 1 year | 5 years |
|---|---|---|---|---|
| Aspirin only cohort | (n = 1,188) | (n = 1,182) | (n = 1,168) | (n = 616) |
| Aspirin only | 719 (60.52%) | 738 (62.44%) | 779 (66.70%) | 411 (66.72%) |
| Single antiplatelet (other than aspirin) | 8 (0.67%) | 9 (0.76%) | 13 (1.11%) | 10 (1.62%) |
| Aspirin + additional antiplatelet | 97 (8.16%) | 94 (7.95%) | 106 (9.08%) | 95 (15.42%) |
| Aspirin + * anticoagulation | 40 (3.37%) | 39 (3.30%) | 34 (2.91%) | 22 (3.57%) |
| † DAPT + * anticoagulation | 1 (0.08%) | 1 (0.08%) | 1 (0.09%) | 3 (0.49%) |
| * Anticoagulation only | 10 (0.84%) | 14 (1.18%) | 13 (1.11%) | 12 (1.95%) |
| No antiplatelet or * anticoagulation | 313 (26.35%) | 287 (24.28%) | 223 (19.09%) | 63 (10.23%) |
| Other | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) |
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