Population and baseline characteristics
The MIMIC III database contains records of 9243 patients undergoing isolated CABG due to CAD, of whom 5969 were excluded because of duplicated or missing records. In the end, 3274 patients were included in this study. Of these, 72.8% (n = 2385) were treated with ASA alone postoperatively, and the rest (n = 889) were treated with ASA and clopidogrel. Moreover, 33.3% of the patients also accepted coagulative therapy after the surgery in both the ASA (n = 794) and DAPT (n = 296) groups.
The baseline characteristics of patients in the ASA and DAPT groups are presented in Table 1. The two groups were balanced regarding most comorbidities, preoperative ASA and heparin use, and postoperative coagulative therapy. The DAPT group had a higher proportion of patients with peripheral artery disease, previous PCI or previous CABG history. Additionally, lower preoperative hemoglobin values and higher preoperative platelet counts were seen in the DAPT group.
Table 1
the baseline characteristics of patients in the ASA and DAPT groups
| ASA group (n = 2385) | DAPT group (n = 889) | p-value |
Age (years) | 67.3 (59.7–74.7) | 66.5 (58.5–74.0) | 0.044 |
Male | 1877 (78.7) | 661 (74.4) | 0.008 |
Weight (kg) | 87.8 (77.5–97.0) | 87.6 (76.8–96.6) | 0.437 |
Smoke | 246 (10.3) | 87 (9.8) | 0.657 |
Hypertension | 1650 (69.2) | 604 (67.9) | 0.495 |
DM | 963 (40.4) | 366 (41.2) | 0.681 |
Dyslipidemia | 1618 (67.8) | 574 (64.6) | 0.077 |
Peripheral artery disease | 96 (4.0) | 81 (9.1) | < .001 |
Cerebrovascular accident | 60 (2.5) | 30 (3.4) | 0.181 |
COPD | 32 (1.3) | 21 (2.4) | 0.040 |
Renal dysfunction | 242 (10.1) | 101 (11.4) | 0.313 |
Dialysis | 13 (0.5) | 2 (0.2) | 0.381 |
Previous PCI | 220 (9.2) | 162 (18.2) | < .001 |
Redo CABG | 28 (1.2) | 29 (3.3) | < .001 |
Emergent operation | 93 (3.9) | 23 (2.6) | 0.071 |
Preoperative laboratory values | | | |
Hb | 11.2 (10.1–12.5) | 10.9 (9.9–12.2) | 0.001 |
Creatinine | 0.9 (0.8–1.1) | 0.9 (0.8–1.1) | 0.939 |
Platelet count | 183.3 (150.6-222.4) | 191.5 (155.6-235.6) | < .001 |
Preoperative ASA | 2334 (97.9) | 872 (98.1) | 0.687 |
Preoperative heparin use | 1098 (46.0) | 402 (45.2) | 0.676 |
Postoperative early use of heparin | 251 (10.5) | 91 (10.2) | 0.811 |
Postoperative coagulation | 794 (33.3) | 296 (33.3) | 0.998 |
DM: diabetes mellitus |
COPD: chronic obstructive pulmonary disease |
PCI: percutaneous coronary intervention |
CABG: coronary artery bypass grafting |
Hb: hemoglobin |
ASA: aspirin |
Primary and secondary outcomes in the ASA and DAPT groups
Differences in the rates of bleeding events in the ASA and DAPT groups are presented in Table 2. Overall, according to the PLATO definitions, major life-threatening bleeding occurred in 15.5% versus 12.9% (p = 0.069) of the patients in the ASA and DAPT groups, respectively. Correspondingly, other major bleeding occurred in 28.8% versus 28.1% (p = 0.7). Bleeding according to the TIMI major criteria occurred in 5.8% versus 5.5% (p = 0.7654) and TIMI minor criteria in 25.0% versus 25.9% (p = 0.623), in the ASA and DAPT groups, respectively. Similarly, the GUSTO severe bleeding rates were 0.9% and 1.5% (p = 0.144). There was no difference in the bleeding-related hemoglobin decrease or reoperation rate between the two groups. Intracranial bleeding was uncommon in both groups. MCTD of > 1 L in the first postoperative hours was more frequent in the DAPT group (4.7% vs 3.1%, p = 0.026). Patients in the DPAT group had a higher rate of platelet transfusion, but a lower rate of PRBC transfusion.
Table 2
the rates of bleeding events in the ASA and DAPT groups
| ASA group (n = 2385) | DAPT group (n = 889) | p-value |
PLATO major bleeding | 1007 (42.2) | 346 (38.9) | 0.088 |
PLATO major life-threatening bleeding | 369 (15.5) | 115 (12.9) | 0.069 |
PLATO other major bleeding | 687 (28.8) | 250 (28.1) | 0.700 |
TIMI major bleeding | 138 (5.8) | 49 (5.5) | 0.764 |
TIMI minor bleeding | 597 (25.0) | 230 (25.9) | 0.623 |
GUSTO severe bleeding | 21 (0.9) | 13 (1.5) | 0.144 |
Intracranial bleeding | 1 (0.0) | 3 (0.3) | 0.064 |
Reoperation due to bleeding | 20 (0.8) | 10 (1.1) | 0.445 |
Bleed resulting in Hb decrease > 50g/L | 138 (5.8) | 49 (5.5) | 0.764 |
Bleed resulting in Hb decrease > 30g/L | 717 (30.1) | 267 (30.0) | 0.987 |
Transfusion PRBC > 4 U | 210 (8.8) | 59 (6.6) | 0.044 |
Transfusion PRBC > 2 U | 271 (11.4) | 71 (8.0) | 0.005 |
PRBC transfusion | 356 (14.9) | 92 (10.3) | 0.001 |
FFP transfusion | 200 (8.4) | 84 (9.4) | 0.336 |
Platelet transfusion | 130 (5.5) | 77 (8.7) | 0.001 |
MCTD > 1 L within 12 h | 74 (3.1) | 42 (4.7) | 0.026 |
Hb: hemoglobin |
PRBC: packed red blood cells |
FFP: fresh frozen plasma |
MCTD: mediastinal chest tube drainage |
The postoperative mortality at 30 days with ASA versus DAPT was 1.4% versus 1.8% (p = 0.437) (Table 3). The rate of postoperative MI was higher in the DAPT group (1.3% versus 0.2%, p < 0.001). A similar result was seen with the occurrence of postoperative stroke (DAPT 2.2% versus ASA 1.3%, p = 0.04). The difference in the rate of postoperative MI and stroke drove an increase in the composite endpoint from 2.7% for the ASA group, to 4.0% for the DAPT group (p = 0.043).
Table 3
the secondary endpoints in the ASA and DAPT groups
| ASA group (n = 2385) | DAPT group (n = 889) | p-value |
Postoperative mortality in 30 d | 34 (1.4) | 16 (1.8) | 0.437 |
Postoperative MI | 5 (0.2) | 12 (1.3) | < .001 |
Stroke | 30 (1.3) | 20 (2.2) | 0.040 |
Composite end point | 64 (2.7) | 36 (4.0) | 0.043 |
MI: myocardial infarction |
Subgroup analysis
In the ASA group, 1591 were treated without anticoagulative therapy (subgroup 1), while 794 were treated with either heparin, LMWH, warfarin or a combination thereof (subgroup 3). Similarly, 593 patients in the DAPT group did not have any anticoagulative therapy (subgroup 2), while 296 received DAPT plus anticoagulative medication (subgroup 4). Significant increases were seen in the rates of PLATO major life-threatening bleeding, TIMI major bleeding and GUSTO severe bleeding in patients treated with ASA and anticoagulative therapy (subgroup 3) compared with non-anticoagulative ASA treatment (subgroup 1) (Table 4). Patients in subgroup 3 also had higher rates of reoperation, hemoglobin decrease, PRBC transfusion, and platelet transfusion due to bleeding than subgroup 1. Similarly, patients in subgroup 4 showed higher rates of PLATO major bleeding, TIMI minor bleeding, hemoglobin decrease, PRBC and platelet transfusion due to bleeding than subgroup 2. In addition, a minority of the patients in this study were given heparin within 48 postoperative hours (n = 342, 10.4%), who had significantly higher rates of PLATO major bleeding, TIMI major and minor bleeding, bleeding-related hemoglobin decrease and PRBC transfusion (Table 5).
Table 4
the rates of bleeding events in the subgroups
| Subgroup 1: ASA (n = 1591) | Subgroup 2: DAPT (n = 593) | Subgroup 3: ASA-anticoag (n = 794) | Subgroup 4: DAPT-anticoag (n = 296) | p-value 1 vs. 2 | p-value 3 vs. 4 | p-value 1 vs. 3 | p-value 2 vs. 4 |
PLATO major bleeding | 599 (37.6) | 208 (35.1) | 408 (51.4) | 138 (46.6) | 0.268 | 0.162 | < .001 | 0.001 |
PLATO major life-threatening bleeding | 177 (11.1) | 67 (11.3) | 192 (24.2) | 48 (16.2) | 0.909 | 0.005 | < .001 | 0.039 |
PLATO other major bleeding | 447 (28.1) | 149 (25.1) | 240 (30.2) | 101 (34.1) | 0.166 | 0.217 | 0.279 | 0.005 |
TIMI major bleeding | 76 (4.8) | 32 (5.4) | 62 (7.8) | 17 (5.7) | 0.553 | 0.242 | 0.003 | 0.831 |
TIMI minor bleeding | 394 (24.8) | 138 (23.3) | 203 (25.6) | 92 (31.1) | 0.470 | 0.068 | 0.670 | 0.012 |
GUSTO severe bleeding | 8 (0.5) | 7 (1.2) | 13 (1.6) | 6 (2.0) | 0.139 | 0.662 | 0.005 | 0.376 |
Intracranial bleeding | 0 (0.0) | 1 (0.2) | 1 (0.1) | 2 (0.7) | 0.272 | 0.181 | 0.333 | 0.259 |
Reoperation due to bleeding | 8 (0.5) | 6 (1.0) | 12 (1.5) | 4 (1.4) | 0.226 | 0.845 | 0.011 | 0.738 |
Bleed resulting in Hb decrease > 50g/L | 76 (4.8) | 32 (5.4) | 62 (7.8) | 17 (5.7) | 0.553 | 0.242 | 0.003 | 0.831 |
Bleed resulting in Hb decrease > 30g/L | 457 (28.7) | 165 (27.8) | 260 (32.7) | 102 (34.5) | 0.679 | 0.593 | 0.044 | 0.042 |
Transfusion PRBC > 4 U | 81 (5.1) | 32 (5.4) | 129 (16.2) | 27 (9.1) | 0.775 | 0.003 | < .001 | 0.035 |
Transfusion PRBC > 2 U | 123 (7.7) | 38 (6.4) | 148 (18.6) | 33 (11.1) | 0.293 | 0.003 | < .001 | 0.014 |
PRBC transfusion | 173 (10.9) | 47 (7.9) | 183 (23.0) | 45 (15.2) | 0.042 | 0.005 | < .001 | 0.001 |
FFP transfusion | 112 (7.0) | 49 (8.3) | 88 (11.1) | 35 (11.8) | 0.330 | 0.731 | 0.001 | 0.087 |
Platelet transfusion | 82 (5.2) | 42 (7.1) | 48 (6.0) | 35 (11.8) | 0.083 | 0.001 | 0.366 | 0.018 |
MCTD > 1 L within 12 h | 46 (2.9) | 25 (4.2) | 28 (3.5) | 17 (5.7) | 0.121 | 0.102 | 0.399 | 0.312 |
ASA: aspirin |
DAPT: dual antiplatelet therapy |
Hb: hemoglobin |
PRBC: packed red blood cells |
FFP: fresh frozen plasma |
MCTD: mediastinal chest tube drainage |
Table 5
early use of heparin and the rates of bleeding events
| Heparin not early used (n = 2932) | Heparin early used (n = 342) | p-value |
PLATO major bleeding | 1155 (39.4) | 198 (57.9) | < .001 |
PLATO major life-threatening bleeding | 397 (13.5) | 87 (25.4) | < .001 |
PLATO other major bleeding | 806 (27.5) | 131 (38.3) | < .001 |
TIMI major bleeding | 146 (5.0) | 41 (12.0) | < .001 |
TIMI minor bleeding | 712 (24.3) | 115 (33.6) | < .001 |
GUSTO severe bleeding | 30 (1.0) | 4 (1.2) | 0.776 |
Intracranial bleeding | 3 (0.1) | 1 (0.3) | 0.357 |
Reoperation due to bleeding | 27 (0.9) | 3 (0.9) | 0.936 |
Bleed resulting in Hb decrease > 50g/L | 146 (5.0) | 41 (12.0) | < .001 |
Bleed resulting in Hb decrease > 30g/L | 830 (28.3) | 154 (45.0) | < .001 |
Transfusion PRBC > 4 U | 220 (7.5) | 49 (14.3) | < .001 |
Transfusion PRBC > 2 U | 289 (9.9) | 53 (15.5) | 0.001 |
PRBC transfusion | 378 (12.9) | 70 (20.5) | < .001 |
FFP transfusion | 250 (8.5) | 34 (9.9) | 0.379 |
Platelet transfusion | 189 (6.4) | 18 (5.3) | 0.395 |
MCTD > 1 L within 12 h | 105 (3.6) | 11 (3.2) | 0.730 |
Hb: hemoglobin |
PRBC: packed red blood cells |
FFP: fresh frozen plasma |
MCTD: mediastinal chest tube drainage |
Multivariable analysis of bleeding-related events and postoperative adverse events
Logistic regression was performed to ascertain antithrombotic strategies predictive of bleeding-related events and postoperative adverse events (Table 6). Neither preoperative use of ASA nor postoperative use of DAPT was a predictive factor for major or severe bleeding according to PLATO, TIMI or GUSTO. In contrast, postoperative anticoagulant therapy independently predicted PLATO major bleeding (OR: 1.49; 95% CI: 1.26–1.76; p < 0.001), GUSTO severe bleeding (OR: 2.98; 95% CI: 1.44–6.15; p = 0.003), and bleeding-related reoperation (OR: 2.80; 95% CI: 1.30–6.03; p = 0.008). Similarly, postoperative use of heparin within 48 hours was a predictive factor for PLATO major bleeding (OR: 1.61; 95% CI: 1.24–2.09; p < 0.001) and TIMI major bleeding (OR: 2.53; 95% CI: 1.59–4.03; p < 0.001).
Table 6
multivariable analysis of bleeding-related events
| PLATO major | TIMI major | GUSTO severe | drainage > 1000mL/12h | Reoperation |
| OR (95%CI) | p value | OR (95%CI) | p value | OR (95%CI) | p value | OR (95%CI) | p value | OR (95%CI) | p value |
Pre. ASA | 1.16 (0.70–1.91) | 0.573 | 0.79 (0.35–1.81) | 0.575 | 0.76 (0.10-6.00) | 0.791 | 0.59 (0.18–2.01) | 0.402 | 0.52 (0.06–4.29) | 0.547 |
Pre. DAPT | 1.34 (1.09–1.65) | 0.006 | 0.84 (0.53–1.34) | 0.469 | 1.43 (0.59–3.50) | 0.429 | 1.98 (1.22–3.23) | 0.006 | 2.12 (0.82–5.47) | 0.120 |
Post. DAPT | 0.78 (0.65–0.92) | 0.004 | 1.00 (0.70–1.44) | 0.999 | 1.48 (0.69–3.21) | 0.318 | 1.21 (0.78–1.89) | 0.390 | 0.99 (0.41–2.38) | 0.986 |
Post. Anticoagulant therapy | 1.49 (1.26–1.76) | < .001 | 1.01 (0.69–1.48) | 0.945 | 2.98 (1.44–6.15) | 0.003 | 1.46 (0.96–2.23) | 0.078 | 2.80 (1.30–6.03) | 0.008 |
Post. heparin early use | 1.61 (1.24–2.09) | < .001 | 2.53 (1.59–4.03) | < .001 | 0.60 (0.19–1.88) | 0.378 | 0.76 (0.37–1.55) | 0.456 | 0.55 (0.15–2.02) | 0.367 |
Redo CABG | 1.54 (0.90–2.62) | 0.114 | 2.43 (1.07–5.52) | 0.034 | 1.37 (0.18–10.37) | 0.762 | 0.85 (0.20–3.55) | 0.820 | 1.63 (0.21–12.40) | 0.637 |
Previous PCI | 1.17 (0.94–1.46) | 0.160 | 0.71 (0.42–1.21) | 0.208 | 0.91 (0.31–2.62) | 0.857 | 0.94 (0.53–1.67) | 0.833 | 1.09 (0.37–3.20) | 0.871 |
OR: odds ratio |
ASA: aspirin |
DAPT: dual antiplatelet therapy |
CABG: coronary artery bypass grafting |
PCI: percutaneous coronary intervention |
Postoperative DAPT was associated with higher risk of MI (OR: 8.35; 95% CI: 2.83–24.65; p < 0.001) and stroke (OR: 2.29; 95% CI: 1.26–4.18; p = 0.007); but was not a predictive factor of increased mortality within 30 days (OR: 0.98; 95% CI: 0.50–1.90; p = 0.943). Moreover, postoperative use of heparin within 48 hours was significantly associated with increased mortality within 30 days, a higher risk of stroke, and the occurrence of the composite endpoint (Table 7).
Table 7
multivariable analysis of postoperative adverse events
| Composite end point | 30 d mortality | MI | Stroke |
| OR (95%CI) | p value | OR (95%CI) | p value | OR (95%CI) | p value | OR (95%CI) | p value |
Pre. ASA | 0.61 (0.23–1.60) | 0.313 | 1.70 (0.22–12.92) | 0.611 | 0.24 (0.05–1.21) | 0.083 | 0.48 (0.14–1.64) | 0.242 |
Pre. DAPT | 0;.86 (0.48–1.54) | 0.612 | 2.19 (1.10–4.39) | 0.026 | 0.58 (0.16–2.14) | 0.409 | 0.43 (0.16–1.15) | 0.093 |
Post. DAPT | 1.64 (1.05–2.57) | 0.031 | 0.98 (0.50–1.90) | 0.943 | 8.35 (2.83–24.65) | < .001 | 2.29 (1.26–4.18) | 0.007 |
Post. Anticoagulant therapy | 2.83 (1.80–4.45) | < .001 | 2.96 (1.53–5.73) | 0.001 | 2.83 (0.91–8.88) | 0.074 | 3.55 (1.92–6.57) | < .001 |
Post. heparin early use | 1.25 (0.72–2.16) | 0.432 | 1.81 (0.88–3.71) | 0.105 | 1.61 (0.47–5.50) | 0.446 | 0.71 (0.31–1.62) | 0.411 |
Redo CABG | 1.43 (0.43–4.78) | 0.559 | 2.38 (0.55–10.31) | 0.245 | 0.88 (0.21–3.16) | 0.745 | 0.80 (0.11–6.01) | 0.824 |
Previous PCI | 0.70 (0.35–1.41) | 0.318 | 0.61 (0.22–1.72) | 0.348 | 0.37 (0.05–2.84) | 0.340 | 0.61 (0.22–1.72) | 0.347 |
OR: odds ratio |
ASA: aspirin |
DAPT: dual antiplatelet therapy |
CABG: coronary artery bypass grafting |
PCI: percutaneous coronary intervention |