Low-dose rivaroxaban (Xarelto) didn’t improve bypass graft outcomes in a COMPASS substudy whether given alone or with aspirin, although researchers suggested a signal for benefit consistent with the main trial.
Graft failure within the first year occurred at similar rates after coronary artery bypass graft (CABG) surgery among patients on rivaroxaban vs aspirin alone (7.8% vs 8.0%, OR 0.95, 95% CI 0.67-1.33) or in combination with aspirin (9.1% vs 8.0% with aspirin alone, OR 1.13, 95% CI 0.82-1.57).
The combination did trend toward fewer cardiovascular deaths, strokes, and MIs over 23 months compared to those on aspirin alone without this reaching statistical significance (2.4% vs 3.5%, HR 0.69, 95% CI 0.33-1.47).
The CABG substudy was directionally consistent with the COMPASS trial overall, reported Andre Lamy, MD, of McMaster University in Hamilton, Ontario, in a paper in the Jan. 22 issue of the Journal of the American College of Cardiology.
“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] major adverse cardiovascular events.”
Guidelines currently recommend antiplatelet therapy after CABG with aspirin or clopidogrel (Plavix) to prevent graft failure and improve clinical outcomes.
COMPASS-CABG was a substudy of patients enrolled into the COMPASS trial within 2 weeks following CABG. Participants were randomized to aspirin 100 mg once daily (n=463) alone or in combination with rivaroxaban 2.5 mg twice daily (n=502), or to rivaroxaban alone at 5 mg twice daily (n=483).
Major bleeding in the first 30 days occurred at similar rates among groups (0.4% for rivaroxaban plus aspirin, 0.2% for rivaroxaban alone, and 1.1% for aspirin alone). None of these serious bleeding complications were fatal or led to reoperation or cardiac tamponade.
Beyond those first 30 days, major bleeding rates were no different whether ultra low-dose rivaroxaban was added to aspirin or not. Rivaroxaban alone, however, led to more of major bleeds after the first 30 days (3.9% vs 1.7% for aspirin alone, HR 2.43, 95% CI 1.06-5.54).
“This suggests that it is safe to add rivaroxaban 2.5 mg twice daily to aspirin soon after surgery,” Lamy and colleagues wrote.
From the larger COMPASS trial, the investigators had reported that combining rivaroxaban and aspirin resulted in less MACE in a population with stable coronary artery disease or peripheral artery disease.
Compared with the rest of the trial population, the CABG group in the present analysis was younger and had different risk factors.
Importantly, some patients in COMPASS-CABG started rivaroxaban as early as 4 days after CABG without serious bleeding complications, which “is clinically important because many patients with an indication for oral anticoagulation early after CABG are currently treated with warfarin because of its slower onset and theoretical reversibility,” according to John Alexander, MD, MHS, of Duke Clinical Research Institute in Durham, North Carolina.
Ultimately, the antithrombotics are for the patient and not for the bypass graft, he emphasized in an accompanying editorial. “Not all bypass graft failure leads to an adverse clinical event, and not all clinical events following CABG are caused by graft failure,” Alexander wrote.
“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,” he suggested.
Given that COMPASS had been stopped early and that approximately 20% of study participants did not get follow-up CT angiography, low power might be to blame for the lack of difference in graft patency among the three treatment arms, Lamy’s group theorized.
“On the basis of the available evidence, how should one approach antithrombotic therapy following CABG? 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.”
Unless there’s a clear indication for it, triple therapy (aspirin, ticagrelor, and oral anticoagulation) should be avoided because of its tie to a high risk of bleeding, the editorialist warned.
The COMPASS trial was supported by Bayer.
Lamy disclosed no conflicts of interest.
Co-authors reported multiple ties to industry.
Alexander reported getting institutional research grants from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, CryoLife, CSL Behring, the FDA, the NIH, Sanofi, Tenax, and VoluMetrix; and has received consulting fees and honoraria from Abbvie, Bristol-Myers Squibb, CSL Behring, Janssen, Pfizer, Portola, Teikoku, the VA Cooperative Studies Program, and Zafgen.