Abstract
Background
The aim of this study wasto evaluate the clinical effects of preoperative antiplatelet therapy (APT) discontinuation timing on major bleeding and adverse cardiac events in patients undergoing coronary artery bypass grafting (CABG).
Methods
This retrospective cohort study analyzed data from Fuwai Cardiac Surgery Database (FCSD), specifically from 41,689 patients with acute coronary syndrome undergoing isolated CABG (2009–2019). A comparison was conducted between 10,739 patients treated with continuation APT (AP group; discontinued ≤7 days preoperation; including aspirin alone, clopidogrel alone, or aspirin + clopidogrel) and 30,950 patients with discontinuation therapy (NAP group; >7 days preoperation). Major bleeding events were defined according to the Bleeding Academic Research Consortium-CABG criteria. Composite adverse events (30-day all-cause mortality, stroke, myocardial infarction, and acute renal failure) were assessed. Multivariable logistic regression was applied to estimate effects.
Results
Adverse cardiac events occurred in 7.8% of patients in the AP group and 9.1% in the NAP group (P<0.001), but there was no difference in the incidence of major bleeding events. Multivariable analysis showed that continuation therapy significantly decreased the risk of adverse cardiac events [odds ratio (OR) 0.832; 95% confidence interval (CI): 0.754–0.918; P<0.001] without increasing the risk of major bleeding events (OR 1.006; 95% CI: 0.926–1.093; P=0.88). Subgroup analysis identified certain strategies for reducing adverse events without bleeding.
Conclusions
Preoperative continued APT significantly reduces the risk of 30-day adverse cardiac events post-CABG without increasing the risk of major bleeding. Optimal strategies include clopidogrel alone (discontinued <3 days preoperatively) and dual-antiplatelet therapy (aspirin + clopidogrel discontinued 5–7 days preoperatively).
Keywords: Preoperative antiplatelet strategy, coronary artery bypass grafting (CABG), major bleeding events, adverse cardiac events
Highlight box.
What is known and what is new?
• Preoperative dual-antiplatelet therapy (DAPT) reduces ischemic risks in patients with acute coronary syndrome but inherently increases the risk of perioperative bleeding during coronary artery bypass grafting (CABG). Current international guidelines present divergent or nonspecific recommendations regarding the exact timing of antiplatelet treatment (APT) discontinuation before surgery.
• Through an analysis of a high-volume national registry of 41,689 patients, this study demonstrated that continuing antiplatelet administration up to surgery (discontinuation ≤7 days) significantly elevates the risk of severe postoperative bleeding without offering additional protection against 30-day mortality or acute myocardial infarction. Furthermore, different management schemes (e.g., aspirin alone or clopidogrel alone versus combined DAPT) have slight distinctions in safety profiles, highlighting the importance of determining the specific safety thresholds of antiplatelet timing.
What is the implication, and what should change now?
• These findings support a standardized, strategy-specific preoperative discontinuation window for mitigating severe bleeding without exposing the coronary vasculature to excessive thrombotic hazards. Clinicians should tailor the cessation timeline to the specific antiplatelet agent used, which would facilitate refined, risk-stratified perioperative pathways in modern cardiac surgical practice.
Introduction
Antiplatelet therapy (APT) is a well-established therapy for reducing the risk of recurrent adverse cardiac events after coronary artery bypass grafting (CABG) surgery (1). However, APT also increases the risk of perioperative bleeding complications after CABG. Indeed, deciding between interrupted preoperative APT and continued APT remains controversial. A key determining factor in selecting a preoperative antiplatelet strategy is the timing of discontinued antiplatelet therapy before CABG.
Although current revascularization guidelines recommend discontinued APT (2), the studies related to this subject have reported conflicting results. Some research indicates that continued APT before surgery does not increase the incidence of major bleeding complications (3-5), while other work has found that continued APT is associated with a significantly increased risk of bleeding complications (4,6). However, few studies have examined the effect of preoperative ATP discontinuation timing on major bleeding and adverse cardiac events in patients treated with CABG.
Therefore, we collected data from 41,689 consecutive patients with acute coronary syndrome and compared the effect of preoperative continuation and discontinuation APT on CABG-associated major bleeding and adverse cardiac events. Moreover, strategies for preoperative continuation of APT were stratified into three distinct categories: aspirin alone (AA), clopidogrel alone (CA), and DAPT combining aspirin with clopidogrel (AC). Based on these classifications, we sought to determine the optimal discontinuation timing to achieve a reasonable balance between postoperative bleeding complications and major adverse cardiac events. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-0597/rc).
Methods
Ethics statement
The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This study was approved by the Ethics Committee of Fuwai Hospital (approval No. 2017-887; July 4, 2017). The requirement for informed consent was waived due to the retrospective nature of the analysis.
Study population
Consecutive patients with acute coronary syndrome (n=41,689) undergoing isolated CABG at Fuwai Hospital [Beijing, China; 2009–2019] were included in the analysis. Patients requiring concomitant cardiac or aortic surgery were excluded. All patients underwent first-time isolated CABG surgery. The patients were divided into a (I) continuation group (AP group; n=10,739), which included treatment with AA, CA, or AC within 7 days before CABG; and (II) a discontinuation group (NAP group; n=30,950), in which no antiplatelet agents were administered within 7 days before CABG. Agents were administered at standard doses (aspirin: 100 mg/d; clopidogrel: 300 mg/d and then 75 mg/d). For nonemergent surgery, antiplatelets were stopped ≥12 hours before the operation, typically with low-molecular-weight heparin bridging. CABG was performed with standard techniques (on-/off-pump selected as per surgeon preference).
Study design and data collection
We conducted a retrospective analysis based on observational data. Patient data were retrieved from the institutional database, which contained information of all consecutive patients undergoing CABG, including demographics, patient history, preoperative medications, intraoperative data, perioperative imaging data (e.g., echocardiography and computed tomography), postoperative cardiocerebral events, renal failure, and 30-day all-cause mortality. Patients were stratified into two groups based on the timing of preoperative antiplatelet discontinuation within 7 days before CABG: the AP group (≤7 days preoperation; n=10,739) and the NAP group (>7 days preoperation; n=30,950). This 7-day threshold was selected as it is routine clinical practice at our institution. To assess the effect of discontinuation timing on outcomes, the continued therapy group (n=10,739) was further stratified according to antiplatelet agent type and timing of discontinuation before surgery as follows: AA (n=1,320), including discontinuation <3 days (n=669), 3–5 days (n=355), and 5–7 days (n=296) before surgery; CA (n=1,831), including discontinuation <3 days (n=720), 3–5 days (n=616), and 5–7 days (n=495) before surgery; and AC (n=7,587), including discontinuation <3 days (n=2,712), 3–5 days (n=2,829), and 5–7 days (n=2,046) before surgery.
Surgical procedures and clinical management
All patients received standard anesthesia and median sternotomy. Conduits (internal mammary artery and saphenous vein) were harvested under direct vision. For on-Pump CABG, cardiopulmonary bypass (CPB) was conducted with moderate systemic hypothermia (28–32 ℃) and antegrade cold crystalloid cardioplegia. Heparin was administered to achieve an activated clotting time (ACT) ≥480 seconds before CPB, and aortic cross-clamping was used. For off-pump CABG, an Octopus Evolution stabilizer was used (Medtronic, Minneapolis, MN, USA). Heparin was administered to achieve an ACT of 300–350 seconds before anastomosis, and a partial occlusion clamp was used. Conversion to CPB occurred if hemodynamic instability/arrhythmias occurred. The internal thoracic artery was preferentially grafted to the left anterior descending artery, and other conduits (artery/vein) were used for the remaining targets. Proximal anastomoses were performed on the aorta during the reperfusion phrase or after grafting. Protamine was administered to reverse heparin following CPB or completion of grafting. Tranexamic acid was administered intraoperatively unless contraindicated. Postoperative aspirin administration (100 mg/d) was started within 24 hours. Reoperation for bleeding was indicated if chest drainage exceeded 200 mL/h within the first 3 hours or 300 mL/h thereafter or if clinical signs of cardiac tamponade were present. Reoperation for bleeding was considered if >200 mL/h (first 3 h) or >300 mL/h (any time) or if tamponade signs were present. Red blood cell (RBC) transfusion was initiated if the hemoglobin level was <8.0 g/dL pre- or post-CPB or <7.0 g/dL during CPB. Preoperative antiplatelet management strategies and the timing of surgical intervention were determined in accordance with individual patient risk profiles via multidisciplinary discussion and at the discretion of the surgical and cardiological teams.
Study outcomes
The primary outcome was composite adverse events, which consisted of all-cause mortality, stroke, myocardial infarction, and acute renal failure during the first 30 postoperative days. The diagnosis of key outcomes (especially myocardial infarction and stroke) was routinely verified by a senior clinician or a dedicated clinical event committee as part of our institutional quality control process. CABG-related myocardial infarction was defined as an elevation of cardiac biomarker values >10 times the 99th percentile upper reference limit with normal baseline cardiac troponin values (≤99th percentile upper reference limit) plus either new pathological Q waves, an angiographically confirmed new bypass graft or native coronary artery occlusion, or echocardiographic evidence of a new loss of viable myocardium or new regional wall motion abnormality. We defined acute renal failure as a 100% increase in serum creatinine levels (doubling from baseline levels) (7). Secondary outcomes were major bleeding events, which were defined according to published definitions, including Bleeding Academic Research Consortium (BARC) type 4 and CABG-related bleeding (bleeding resulting in death, reoperation due to bleeding, or intracranial hemorrhage; transfusion of 5 or more units of RBCs over 48 hours; or chest tube drainage in excess of 2,000 mL over 24 hours) (8). Acute surgery was defined as a procedure starting within 24 hour of acceptance.
Statistical analysis
Statistical analysis was performed with SPSS 24.0 (IBM Corp., Armonk, NY, USA). Frequencies were derived for categorical variables. Continuous variables are presented as the mean and standard deviation or as the median and interquartile range (IQR) (when not normally distributed). Categorical variables were compared with the Chi-squared test or Fisher exact test as appropriate and are expressed the frequency with percentage; continuous variables were compared with the Student unpaired t-test or the Wilcoxon rank-sum test as appropriate. Multivariable binary logistic regression analysis was performed to adjust for composite adverse events and bleeding-related complications, thereby reducing treatment selection bias and potential confounding. Given our exceptionally extensive sample size of 41,689 consecutive patients, this fully adjusted multivariable regression model could provide highly stable risk tracking. Although nonrandomized designs theoretically benefit from methods such as inverse probability of treatment weighting, our comprehensive adjustment for all baseline factors with a high P value could ensure robust control over selection bias, yielding highly dependable estimations within this high-volume volume cohort. Cases with missing data for any of the key variables included in the multivariable models were excluded from the analysis. Given the retrospective nature of this study and use of an institutional database, loss to follow-up was assumed to be minimal, as major adverse events would likely be captured within the hospital system. However, we acknowledge that events occurring elsewhere might not have been recorded.
Results
Patient characteristics
After patients who underwent concomitant cardiac surgery were excluded, 10,739 (25.8%) patients who continued on antiplatelet within 7 days prior to CABG (AP group) and 30,950 (74.2%) with antiplatelet treatment stopped for more than 7 days prior to CABG (NAP group) were included. The demographic and basic characteristics of these patients are summarized in Table 1. In brief, compared to the NAP group, the AP group had a higher proportion of males and patients with have a history of cerebrovascular accident (14.3% vs. 12.7%; P<0.001), peripheral vascular disease (10.7% vs. 9.3%; P<0.001), and hypertension (66.9% vs. 60.2%; P<0.001); meanwhile, patients in the AP group had a greater prevalence of left main coronary artery disease (23.6% vs. 9.9%, P<0.001) and higher median score for European System for Cardiac Operative Risk Evaluation (EuroSCORE; AP: 2, IQR 0.0–3.0; NAP: 1, IQR 0.0–3.0; P<0.001). Patients in the AP group, compared with those patients in the NAP group, more often required acute surgery (4.3% vs. 3.9%), but this difference was not significant (P=0.07). Moreover, there were no statistically significant differences in age, off-pump CABG, preoperative hemoglobin level, and preoperative left ventricular ejection fraction (LVEF) (%) between the two groups. All patients had 30-day follow-up data available in the institutional database.
Table 1. Demographics and procedural characteristics.
| Characteristic | AP group (n=10,739) | NAP group (n=30,950) | P value |
|---|---|---|---|
| Age (years) | 61.3±8.7 | 61.3±8.7 | 0.99 |
| BMI (kg/m2) | 25.0±3.1 | 25.8±3.1 | 0.99 |
| Female | 2,366 (22.0) | 7,249 (23.4) | <0.001 |
| Anamnesis | |||
| Diabetes | 3,739 (34.8) | 10,598 (34.2) | 0.28 |
| CVA | 1,537 (14.3) | 3,923 (12.7) | <0.001 |
| PVD | 1,149 (10.7) | 2,877 (9.3) | <0.001 |
| Hypertension | 7,192 (66.9) | 18,640 (60.2) | <0.001 |
| CHF | 72 (0.7) | 251 (0.8) | 0.15 |
| Chronic renal dysfunction | 98 (0.9) | 238 (0.8) | 0.15 |
| Carotid thrombosis | 798 (7.4) | 2,243 (7.2) | 0.53 |
| Cardiac surgery history | 364 (3.4) | 953 (3.1) | 0.11 |
| Preoperative LVEF (%) | 60.7±8.3 | 59.4±9.1 | 0.91 |
| Standard EuroSCORE | 2 [0.0–3.0] | 1 [0.0–3.0] | <0.001 |
| Preoperative lab test | |||
| HB (g/L) | 133.6±14.7 | 134.7±15.2 | 0.90 |
| PLT count (109/L) | 204.3±54.1 | 208.7±58.7 | 0.89 |
| APTT (s) | 12.9±0.8 | 13.3±1.0 | 0.89 |
| MI | 3,568 (33.2) | 10,125 (32.7) | 0.33 |
| CABG characteristic | |||
| Acute CABG | 466 (4.3) | 1,222 (3.9) | 0.07 |
| Off plump CABG | 3,974 (37.0) | 11,516 (37.2) | 0.75 |
| Triple vessels disease | 8,742 (81.4) | 24967 (80.7) | 0.09 |
| Left main coronary artery disease | 2,536 (23.6) | 3,057 (9.9) | <0.001 |
| Valve operation | 8,742 (81.4) | 22467 (72.6) | 0.09 |
| Distal anastomoses | 5 [5.0–6.0] | 4 [4.0–5.0] | 0.18 |
| IMA graft | 10,072 (93.8) | 28,967 (93.6) | 0.47 |
| RA graft | 212 (1.9) | 628 (2.0) | 0.73 |
| SVG graft | 9,708 (90.4) | 27,947 (90.3) | 0.10 |
Data are presented as n (%), mean ± standard deviation or median [interquartile range]. Valve operation: associated mitral, tricuspid, aortic, and pulmonary valve operation. ACEI, angiotensin-converting enzyme inhibitor; AP, preoperative antiplatelet continuation therapy; APTT, activated partial thromboplastin time; BMI, body mass index; CABG, coronary artery bypass grafting; CHF, congestive heart failure; CVA, cerebrovascular accident; EuroSCORE, European System for Cardiac Operative Risk Evaluation; HB, hemoglobin; IMA, internal mammary artery; LVEF, left ventricular ejection fraction; MI, myocardial infarction; NAP, discontinuation preoperative antiplatelet therapy; PLT, platelet; PVD, peripheral vascular disease; RA, radial artery; SVG, saphenous vein graft.
Study outcomes
No statistically significant differences in CPB, operative time, or mechanical ventilation time were observed between the two groups. A greater portion of patients in the AP group needed intra-aortic balloon pump as compared to the NAP group (3.2% vs. 2.1%; P<0.001), but there was no significant difference in postoperative hospital stay. The primary outcome of composite adverse event occurred in 834 (7.8%) patients in the AP group and in 2,806 (9.1%) in the NAP group (P<0.001). Compared with the NAP group, the AP group had a significantly lower prevalence of stroke (0.4% vs. 0.7%; P<0.001) and myocardial infarction (3.7% vs. 4.3%, P=0.01) in the initial 30-day postoperative period. There were no significant differences in death or acute renal failure at 30 days between these two groups. Moreover, no significant differences in the incidence of major bleeding events was found between the two groups (AP group: 837 cases, 7.8%; NAP group: 2,341 cases, 7.6%; P=0.44). The difference in the rates of bleeding resulting in death, chest tube drainage in excess of 2,000 mL over 24 hours, transfusion of 5 or more units of RBCs over 48 hours, and reoperation due to bleeding between the AP and NAP groups did not reach statistical significance. The details of the outcomes are provided in Table 2.
Table 2. Postoperative outcomes.
| Variable | AP group (n=10,739) | NAP group (n=30,950) | P value |
|---|---|---|---|
| CPB time (min) | 89.6±47.7 | 88.7±42.8 | 0.94 |
| Operative time (min) | 275.8±77.7 | 287.9±82.1 | 0.98 |
| MVT (h) | 12.50 [0.00–17.17] | 12.20 [0.00–17.25] | 0.36 |
| Re-operation | 156 (1.45) | 413 (1.33) | 0.36 |
| Postoperative stay (days) | 8.04±4.41 | 8.14±4.64 | 0.98 |
| ECMO | 14 (0.13) | 45 (0.15) | 0.72 |
| IABP | 347 (3.2) | 657 (2.1) | <0.001 |
| Composite adverse events | 834 (7.8) | 2,806 (9.1) | <0.001 |
| Death | 21 (0.20) | 74 (0.24) | 0.34 |
| Postoperative stroke | 43 (0.4) | 220 (0.7) | <0.001 |
| Postoperative MI | 402 (3.7) | 1,348 (4.3) | 0.01 |
| Acute renal failure | 368 (3.4) | 1,164 (3.8) | 0.11 |
| Main bleeding events | 837 (7.8) | 2,341 (7.6) | 0.44 |
| Bleeding resulting in death | 6 (0.05) | 14 (0.04) | 0.62 |
| CTD in 24 hours ≥2,000 mL | 410 (3.82) | 1,105 (3.57) | 0.24 |
| RBC transfusion in 48 hours ≥5 U | 329 (3.06) | 1,025 (3.31) | 0.19 |
| Reoperation due to bleeding | 78 (0.73) | 211 (0.68) | 0.63 |
Data are presented as n (%), mean ± standard deviation or median [interquartile range]. AP, preoperative antiplatelet continuation therapy; CPB, cardiopulmonary bypass; CTD, chest tube drainage; IABP, intra-aortic balloon pump; MI, myocardial infarction; MVT, mechanical ventilation time; NAP, discontinuation preoperative antiplatelet therapy; RBC, red blood cell.
Study outcomes adjusted by multivariable regression analysis
All baseline variables with significantly statistical differences between the two groups, including gender, cerebrovascular accident, peripheral vascular disease, hypertension history, left main coronary artery disease, and preoperative standard EuroSCORE, were included in the multivariable binary logistic regression analysis. Baseline variables identified as influencing the outcome of composite adverse and major bleeding events, including age, acute CABG, preoperative LVEF (%), platelet count, diabetes, and cardiac surgery history, were also incorporated into the multivariable regression model. Continual APT within 7 days before surgery was not a risk factor for major bleeding events [odds ratio (OR) 1.006, 95% confidence interval (CI): 0.926–1.039; P=0.88], while the adjusted risk estimate for composite adverse events confirmed this therapy to be a highly favorable factor in reducing adverse cardiac events (OR 0.832, 95% CI: 0.754–0.918; P<0.001) (Table 3). Multivariable binary logistic regression analysis of subgroups indicated that CA within 3 days and AC within 5–7 days before surgery did not increase risk of major bleeding events (3 days: OR 1.077, 95% CI: 0.787–1.473, P=0.65; 5–7 days: OR 1.164, 95% CI: 0.962–1.407, P=0.12) and reduced the risk of composite adverse events (3 days: OR 0.649, 95% CI: 0.468–0.900, P=0.01; 5–7 days: OR 0.761, 95% CI: 0.614–0.942; P=0.01). AC administered within 3 days before surgery was a risk factor for major bleeding events (OR 1.799; 95% CI: 1.513–2.138; P<0.001) and was not found to decrease the risk of composite adverse events (OR 0.989; 95% CI: 0.818–1.196; P=0.90). Discontinuation therapy with AA at any cutoff time point prior to surgery did not lower the risk of composite adverse events or increase the risk of major bleeding events (Table S1).
Table 3. Factors associated with major bleeding and composite adverse events in the multivariable logistic regression.
| Variable | Major bleeding events | Composite adverse events | ||||||
|---|---|---|---|---|---|---|---|---|
| No (n=38,531) | Yes (n=3,158) | OR (95% CI) | P value | No (n=38,049) | Yes (n=3,640) | OR (95% CI) | P value | |
| Female | 8,832 (22.9) | 783 (24.8) | 1.017 (0.909–1.137) | 0.77 | 8,553 (22.5) | 1,062 (29.2) | 1.142 (1.037–1.258) | 0.01 |
| Age (years) | 61.12±8.68 | 63.68±8.54 | 1.024 (1.017–1.030) | <0.001 | 61.13±8.67 | 63.19±8.73 | 1.001 (0.995–1.006) | 0.89 |
| Hypertension | 23,968 (62.2) | 1,864 (59.0) | 0.919 (0.836–1.009) | 0.08 | 23,369 (61.4) | 2,463 (67.7) | 1.339 (1.223–1.465) | <0.001 |
| Diabetes | 13,211 (34.3) | 1,126 (35.7) | 1.045 (0.952–1.148) | 0.36 | 12,898 (33.9) | 1,439 (39.5) | 1.220 (1.122–1.328) | <0.001 |
| CVA | 4,995 (13.0) | 465 (14.7) | 1.104 (0.973–1.252) | 0.12 | 4,860 (12.8) | 600 (16.5) | 1.220 (1.092–1.362) | <0.001 |
| PVD | 3,743 (9.7) | 284 (9.0) | 0.884 (0.763–1.023) | 0.10 | 3,595 (9.4) | 432 (11.9) | 1.044 (0.919–1.186) | 0.50 |
| Prior cardiac surgery | 1,085 (2.8) | 232 (7.3) | 2.778 (2.323–3.321) | <0.001 | 1,088 (2.9) | 229 (6.3) | 1.731 (1.442–2.078) | <0.001 |
| Acute CABG | 1,173 (3.2) | 315 (5.9) | 1.434 (1.171–1.765) | <0.001 | 1,279 (3.4) | 209 (5.7) | 1.142 (0.944–1.382) | 0.17 |
| Standard EuroSCORE | 1.0 [0.0–3.0] | 2.0 [1.0–4.0] | 1.078 (1.048–1.108) | <0.001 | 1.0 [0.0–3.0] | 2.0 [1.0–4.0] | 1.200 (1.172–1.230) | <0.001 |
| Preoperative LVEF (%) | 61.0 [56.0–65.0] | 60.0 [55.0–65.0] | 0.988 (0.983–0.993) | <0.001 | 59.86±8.81 | 58.14±9.49 | 0.987 (0.983–0.992) | <0.001 |
| Left main coronary artery disease | 5,059 (13.1) | 534 (16.9) | 1.171 (1.034–1.327) | 0.01 | 5,162 (13.6) | 431 (11.8) | 0.947 (0.836–1.073) | 0.39 |
| Preoperative PLT (109/L) | 208.47±57.15 | 192.75±58.12 | 0.996 (0.995–0.996) | <0.001 | 207.43±57.07 | 206.08±60.17 | 1.000 (0.999–1.000) | 0.44 |
| AP | 9,901 (25.8) | 837 (26.5) | 1.006 (0.926–1.093) | 0.88 | 9,905 (26.0) | 834 (23.1) | 0.832 (0.754–0.918) | <0.001 |
Data are presented as n (%), mean ± standard deviation or median [interquartile range]. AP, preoperative antiplatelet continuation therapy; CABG, coronary artery bypass grafting; CI, confidence interval; CVA, cerebrovascular accident; EuroSCORE, European System for Cardiac Operative Risk Evaluation; LVEF, left ventricular ejection fraction; OD, operative duration time; OR, odds ratio; PLT, platelet; PVD, peripheral vascular disease.
Discussion
Preoperative APT is standard in patients treated with CABG but can increase the risk of bleeding events when administered shortly before surgery (9,10). Balancing thrombosis and bleeding risks in patients undergoing CABG is challenging, and the optimal timing for preoperative APT discontinuation remains controversial. This large-sample study (n=41,689) evaluated the impact of preoperative APT on major bleeding and adverse cardiac events. In this protocol, we intentionally evaluated major bleeding and composite adverse events as distinct, independent endpoints, rather than merging them into a single net adverse clinical events) framework. This strategy was used to precisely isolate the dual effects of preoperative medication timing on ischemic risk and bleeding complications, which can occasionally be cross-masked or attenuated in the calculation of a combined net clinical benefit. Subgroup analyses based on discontinuation timing and agents identified strategies for optimizing reductions in bleeding and ischemic risk. However, it remains largely unclear whether aspirin should be continued or stopped before CABG (2,11). Several studies have reported that patients administered aspirin had an increased—albeit small—risk of bleeding (12-14), while other research indicated reductions in mortality and the rate of serious adverse events associated with the preoperative administration of aspirin (15-17). In our study, aspirin was not associated with a decreased risk of death or thrombotic complications or an increased risk of bleeding. The absence of adverse bleeding complications in this study could be explained by the low dose of aspirin administered (100 mg), the use of bridging low-molecular-weight heparin, and the development of aspirin resistance in some patients (18). Our findings were similar to those reported in a recent, multicenter, double-blind, randomized trial aimed at determining whether preoperative aspirin could reduce the occurrence of death and thrombotic complications (19).
There is a significant body of evidence supporting the discontinuation of clopidogrel 5 days prior to CABG (3,20), and this is recommended by the guidelines of European Society of Cardiology (ESC) (1) and American Heart Association/American College of Cardiology (AHA/ACC) (21). However, the bulk of studies assessing bleeding and composite adverse events failed to stratify patients receiving preoperative clopidogrel into monotherapy and combination therapy (CA) subgroups. This omission may introduce selection bias and confounding. Our analysis demonstrated that for clopidogrel monotherapy, discontinuation <3 days preoperatively did not increase major bleeding events and reduced composite adverse events. A subsequent propensity score-adjusted study also indicated no significant association between clopidogrel before CABG and bleeding events (22).
In the Clopidogrel in Unstable Angina to Prevent Recurrent Ischemic Events (CURE) trial, a shorter clopidogrel interruption period did not significantly increase the risk of major bleeding events in patients treated with CABG (23). However, our findings supported continual administration 5–7 days prior to surgery as the ideal cutoff time for clopidogrel DAPT, as this did not increase the risk of major bleeding events while decreasing the risk of composite adverse events. Notably, recent research in interventional cardiology, particularly regarding patients undergoing percutaneous coronary intervention, suggests that balancing acute ischemic events with severe bleeding risk remains a clinical challenge (24). Although our cohort specifically consisted of patients undergoing CABG, the fundamental clinical imperative to avoid systemic thrombotic complications while mitigating bleeding consequences strongly echoes the findings from the field of interventional cardiology.
Limitations
This study involved several limitations that should be addressed. First, we employed an observational design, and thus there is potential for selection bias and the influence of confounders. Although all baseline characteristics with significantly statistical difference between two groups were included in multivariable binary logistic regression analysis to minimize confounding effects, it remains possible that unmeasured confounders contributed to the differences in outcomes. Second, the analyses were based on experience from single-center experience, and thus the conclusions might be influenced by local guidelines and not generalizable to a broader population. Moreover, the limited use of a second arterial graft at our single center may also reduce the applicability of our findings to institutions with different surgical strategies, and our cohort lacked ethnic diversity. Third, due to the retrospective nature of this institutional registry and its data spanning from 2009 to 2019, certain granular elements such as specific acute coronary syndrome subtypes (e.g., ST-segment elevation myocardial infarction vs. non-ST-segment elevation myocardial infarction) were not uniformly or consistently documented across the decade. Consequently, performing comprehensive subgroup analyses for these variables was statistically unfeasible, which limits deeper multilayer evaluation in these specific areas. This may limit the generalizability of our findings to other populations with different genetic backgrounds and healthcare environments. We note that while the composite outcome provides an overall estimate of treatment effect, the interpretation of its clinical relevance should be conducted with caution, and the drivers of the composite should be considered. Finally, the cross-sectional nature of our study precluded an assessment of long-term outcomes due to the lack of follow-up data beyond the perioperative period; meanwhile, the retrospective design precluded formal blinded adjudication of clinical endpoints such as myocardial infarction and stroke, although we relied on prespecified objective criteria to minimize diagnostic bias.
Final remarks and global perspectives
Optimizing preoperative antiplatelet strategies requires a global perspective that balances international guideline recommendations with regional patient characteristics. Western guidelines (such as those from the ACC/AHA and ESC) are primarily derived from randomized controlled trials with predominantly by White populations, and thus their direct extrapolation to East Asian cohorts may not be advisable. Indeed, research has identified an “East Asian paradox” (25), in which East Asian patients, as compared to their Western counterparts, have a different therapeutic window for APT, characterized by a higher susceptibility to bleeding complications despite a lower baseline incidence of ischemic events. In Chinese clinical practice, as represented in our high-volume center, maintaining a tailored approach—in which a shorter discontinuation window is applied under rigorous monitoring—has proven to be highly effective. Future prospective, multinational registry studies are warranted to further refine these antiplatelet protocols across a greater diversity of ethnic and geographical backgrounds.
Conclusions
For patients with acute coronary syndrome undergoing CABG, preoperative continual APT within 7 days decreased the risk of composite adverse events and was found to be safe, as it did not increase the risk of major bleeding events. Continuous administration of AA did not lower the risk of composite adverse events or increase the risk of major bleeding events. CA interruption within 3 days before surgery did not increase the risk of major bleeding event but did decrease the risk of composite adverse events. For the administration of AC, continuous administration within 5–7 days prior to surgery was the ideal cutoff time, as it did not increase the risk of major bleeding events and decreased the risk of composite adverse events.
Supplementary
The article’s supplementary files as
Acknowledgments
The authors would like to thank Xue Zhang and Weinan Chen at the Information Center, Fuwai Hospital, National Center for Cardiovascular Diseases, for their help with data collection.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This study was approved by the Ethics Committee of Fuwai Hospital (approval No. 2017-887; July 4, 2017). The requirement for informed consent was waived due to the retrospective nature of the analysis.
Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-0597/rc
Funding: This study was supported by the National High Level Hospital Clinical Research Funding (grant No. 2023-GSP-RC-07), the National Natural Science Foundation of China (grant Nos. 82470410 and 82370401), the Beijing Outstanding Young Scientist Program (grant No. 2024-BZZQ01), the CAMS Innovation Fund for Medical Sciences (grant No. 2024-I2M-C&T-B-047), and the Fundamental Research Funds for the Central Universities, Peking Union Medical College (grant No. 3332025130).
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-0597/coif). X.W. reports grants from the National High Level Hospital Clinical Research Funding (grant No. 2023-GSP-RC-07), the National Natural Science Foundation of China (grant Nos. 82470410 and 82370401), the Beijing Outstanding Young Scientist Program (grant No. 2024-BZZQ01), and the CAMS Innovation Fund for Medical Sciences (grant No. 2024-I2M-C&T-B-047) during the conduct of the study. The other authors have no conflicts of interest to declare.
(English Language Editor: J. Gray)
Data Sharing Statement
Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-0597/dss
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