Rivaroxaban failed to reduce the rate of early graft failure following coronary artery bypass graft (CABG) surgery compared to aspirin monotherapy, researchers reported in a substudy of the COMPASS trial published Jan. 14 in the Journal of the American College of Cardiology.
That observation applied to both rivaroxaban 2.5 mg twice daily in addition to 100 mg of aspirin and rivaroxaban 5 mg twice daily alone—each studied in related to a 100 mg daily dose of aspirin.
Those same treatment strategies were used in the larger, randomized COMPASS trial, which found patients with stable coronary artery disease or peripheral artery disease were 24 percent less likely to meet the composite endpoint of cardiovascular death, stroke or MI when they were treated with the low-dose rivaroxaban/aspirin combination compared to aspirin alone.
The prespecified COMPASS-CABG substudy randomized 1,448 patients four to 14 days after their CABG operations to one of those dosing regimens, with similar numbers in each group. Graft failure was assessed using CT angiography an average of 1.1 years later. About 22 percent of the patients failed to have their grafts evaluated in this manner, but the investigators were able to study 3,562 grafts from 1,148 patients.
Lead author Andre Lamy, MD, and colleagues found graft failure rates reached 7.8 percent in patients treated with rivaroxaban alone, 8.0 percent in those treated with only aspirin and 9.1 percent in those treated with a combination of rivaroxaban and aspirin. They concluded neither rivaroxaban regimen resulted in reduced odds of graft failure.
However, similar to the overall COMPASS study, CABG patients treated with low doses of the factor Xa inhibitor plus aspirin experienced a 31 percent reduction in major adverse cardiovascular events (MACE) relative to aspirin monotherapy. The overall rates of MACE—cardiovascular death, MI or stroke—were 2.4 percent in the combination therapy group, 3.3 percent in the rivaroxaban alone group and 3.5 percent in the aspirin alone group.
“The number of clinical events in the study was modest, but the overall results were consistent with the main COMPASS study findings in suggesting that rivaroxaban 2.5 mg twice daily plus aspirin compared with aspirin alone will also reduce MACE,” wrote Lamy, with McMaster University in Hamilton, Ontario, Canada, and colleagues. “Rivaroxaban alone compared with aspirin alone did not produce any benefit, which is also consistent with the main COMPASS study results.”
The authors also noted there were few instances of major bleeding—and no cases of fatal bleeding or tamponade—within 30 days of randomization, suggesting “it is safe to add rivaroxaban 2.5 mg twice daily to aspirin soon after surgery.” Patients started on their anticoagulants at the time of randomization, meaning some began their regimens as soon as four days after CABG.
Lamy et al. said a lack of statistical power may have made it more difficult to detect differences in graft occlusion rates between the treatment arms. Those comparisons weren’t helped by the trial stopping early or by roughly 1 in 5 patients foregoing the necessary imaging to assess graft failure.
“Alternatively, it is possible that factor Xa inhibitors do not prevent graft failure because they are relatively ineffective in preventing thrombosis induced by exposure of blood to artificial surfaces such as a venous conduit implanted in an arterial vascular bed,” the authors wrote. “Most patients received at least 1 arterial graft, and these are less likely to occlude than venous grafts, thereby further limiting study power.”
Although the primary outcome of this substudy was graft failure, John H. Alexander, MD, MHS, wrote in a related editorial that it’s still important to consider the treatments’ effects on MACE.
“Despite an absence of effect on graft patency, the clinical outcome results of COMPASS-CABG suggest that the benefits of rivaroxaban on cardiovascular death, stroke, or MI and bleeding observed in the overall COMPASS trial are likely the best estimate of the effect in the subgroup of patients who recently underwent CABG,” wrote Alexander, with the Duke Clinical Research Institute in Durham, North Carolina.
“Because we are treating the whole patient and not just their bypass grafts, the absence of an effect of rivaroxaban on graft patency does not mean it should not be used to prevent recurrent ischemic events following CABG.”
Although he called for more studies to investigate the best antithrombotic regimens following CABG, Alexander offered a few recommendations based on the current evidence.
“Patients should take low-dose aspirin lifelong, unless there is a clear contraindication,” Alexander suggested. “Ticagrelor or low-dose rivaroxaban should be considered as a reasonable addition to aspirin for patients at lower risk of bleeding and higher risk of recurrent ischemic events. In the absence of a clear indication, ‘triple therapy’ with aspirin, ticagrelor, and oral anticoagulation should not be used because of the high associated risk of bleeding.”