Three months of ticagrelor-based dual antiplatelet therapy met the prespecified criterion for noninferiority vs 12 months of therapy for 1-year saphenous vein graft occlusion and reduced clinically relevant bleeding among selected patients undergoing elective coronary artery bypass grafting, according to findings published in The BMJ.
In the TOP-CABG trial, researchers randomly assigned 2,300 patients aged 18 to 80 years undergoing elective primary coronary artery bypass grafting (CABG) with at least 1 saphenous vein graft (SVG) to receive ticagrelor 90 mg twice daily plus aspirin 100 mg once daily for either 3 months or 12 months. Patients in the 3-month group received placebo plus aspirin for the remaining 9 months.
The multicenter, double-blind, placebo-controlled noninferiority trial was conducted at 13 cardiac surgery centers in China between February 2023 and July 2024. Antiplatelet therapy was initiated within 24 hours following surgery to assess early dual antiplatelet therapy (DAPT) intolerance, and patients were randomized on postoperative day 5. Patients unable to tolerate early postoperative DAPT were excluded before randomization.
The trial had 2 primary outcomes: graft-segment-level 100% SVG occlusion at 1 year, tested for noninferiority, and Bleeding Academic Research Consortium type 2, 3, or 5 bleeding within 1 year, tested for superiority. The prespecified noninferiority margin for SVG occlusion was 3.5 percentage points. The researchers described the margin as approximately half the graft-patency benefit previously observed with ticagrelor-based DAPT over aspirin, although they noted that the margin was not based on patient-preference data or a validated threshold for a minimal clinically important difference.
“Among patients undergoing elective CABG with SVG, a three month DAPT strategy had similar one year rates of SVG occlusion while statistically significantly reducing bleeding risk compared with a 12 month DAPT strategy,” wrote lead study author Xin Yuan, of the Department of Cardiovascular Surgery at Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Centre for Cardiovascular Diseases, and colleagues.
The modified intention-to-treat population included 2,290 patients. The mean age was 61.5 years, 21% of patients were women, and 9% had experienced acute coronary syndrome within 2 weeks prior to CABG. Patients received a mean of 2.5 SVG segments each.
At 1 year, outcome assessment was available for 2,070 patients and 5,125 SVG segments. SVG occlusion occurred in 10.8% of graft segments in the 3-month DAPT group and 11.2% of graft segments in the 12-month group, meeting the trial’s criterion for noninferiority. Findings were generally consistent in per-protocol, as-treated, missing-data, patient-level, and per-graft sensitivity analyses.
Bleeding Academic Research Consortium type 2, 3, or 5 bleeding occurred in 8% of patients assigned to 3 months of DAPT compared with 13% of patients assigned to 12 months of therapy. The number needed to treat to prevent 1 clinically relevant bleeding event was 21 in this selected postbypass population.
The bleeding finding was consistent with the trial design. In a landmark analysis, the bleeding difference was not observed within the first 90 days, when both groups received ticagrelor plus aspirin, but emerged after 90 days, when patients in the shorter-duration group had stopped ticagrelor. The researchers noted that SVG occlusion is most likely to occur in the first few months following surgery, when endothelial injury and platelet activation are greatest.
Major adverse cardiovascular and cerebrovascular events, a secondary endpoint defined as cardiac death, myocardial infarction, stroke, or revascularization, occurred in 2.3% of patients in the 3-month group and 2.7% of patients in the 12-month group. However, the trial was not powered for differences in these clinical events, and the hazard ratio of 0.95 had a wide confidence interval of 0.56 to 1.64, leaving uncertainty about potential clinical-event differences.
No statistically significant interactions were observed across prespecified and post hoc subgroup analyses, including analyses stratified by SYNTAX score, SAFINOUS score, Academic Research Consortium for High Bleeding Risk criteria, and PRECISE-DAPT score. However, the subgroup analyses were exploratory, and the trial was not powered to determine whether specific patient groups derived greater or lesser benefit from shorter therapy. The trial also included relatively few patients with recent acute coronary syndrome, limiting conclusions in that population.
The findings may support a shorter ticagrelor-based DAPT strategy among patients undergoing elective CABG with SVGs who are considered appropriate for DAPT and who tolerate early postoperative treatment. However, TOP-CABG did not compare 3 months of DAPT with aspirin monotherapy, and it does not establish whether any DAPT is preferable to aspirin alone in all postbypass patients.
The study adds to an evolving evidence base focused on individualizing antiplatelet therapy following CABG by reducing either treatment intensity or treatment duration. The researchers noted that the TACSI trial tested aspirin monotherapy vs DAPT in patients with acute coronary syndrome following coronary surgery, reporting similar major adverse cardiovascular and cerebrovascular outcomes with less bleeding, whereas the ongoing ODIN trial is testing 1 month of ticagrelor plus aspirin in patients undergoing CABG.
The TOP-CABG findings also should not be extrapolated to all antiplatelet regimens. The trial tested ticagrelor plus aspirin, and the researchers cautioned that conclusions may not apply to clopidogrel-based DAPT or other P2Y12 inhibitors.
The researchers noted several limitations. More than 11% of patients did not fully adhere to the assigned intervention, and some patients did not undergo 1-year graft imaging. About 80% of participants were enrolled from a single center, and all participating centers were in China, which may limit generalizability to other surgical and perioperative settings. Patients unable to tolerate early postoperative DAPT were excluded before randomization, which may have introduced selection bias and limited applicability to patients at higher early bleeding risk. The findings also may not apply to patients with atrial fibrillation requiring anticoagulation, severe renal dysfunction, or intolerance to early postoperative DAPT.
Disclosures: The TOP-CABG trial was funded by the National Clinical Research Centre for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences. Nanjing Zhengda Tianqing Pharmaceutical supplied study drugs. The funders had no role in the design or conduct of the study; data collection, management, analysis, or interpretation; manuscript preparation, review, or approval; or the decision to submit the manuscript for publication. The researchers reported no financial relationships with organizations that might have an interest in the submitted work and no other relationships or activities that could appear to have influenced the submitted work.
Source: The BMJ
