Rivaroxaban plus aspirin a potential new treatment option in PAD
Rivaroxaban in combination with aspirin has emerged as a potential new treatment option for patients with peripheral artery disease (PAD) as late-breaking results from the PAD cohort of the COMPASS trial show significantly reduced rates of major adverse cardiovascular events (MACE) and major adverse limb events (MALE) compared with aspirin alone.
The results, presented at the European Society of Cardiology (ESC) Congress 2017 in Barcelona, Spain, showed a significant 28 percent reduction in the risk of cardiovascular (CV) death, MI or stroke in patients randomized to receive rivaroxaban 2.5 mg twice daily plus aspirin 100 mg daily compared with those who received aspirin alone (5.1 vs 6.9 percent; p=0.005), after a mean follow-up duration of 21 months.
No significant difference in MACE was found, however, between patients who received rivaroxaban 5 mg twice daily and those who received aspirin alone (6 vs 6.9 percent; hazard ratio [HR], 0.86; p=0.19).
“These results, from 7,470 patients with stable PAD of the lower extremities or carotid artery disease, are consistent with overall results of the COMPASS trial,” said Professor Sonia Anand of McMaster University, Hamilton, Canada, who led the PAD component of COMPASS.
“In patients with PAD, the combination of rivaroxaban and aspirin reduced the risk of MI by 24 percent, stroke by 46 percent, and CV mortality by 28 percent compared with aspirin alone,” she reported.
MALE, defined as severe limb ischaemia leading to an intervention and major amputation above the forefoot due to vascular causes, was reduced by 46 percent with rivaroxaban plus aspirin vs aspirin alone (1.2 vs 2.2 percent; p=0.005), while major amputation was reduced by 70 percent (0.2 vs 0.7 percent; p=0.01). With rivaroxaban monotherapy, the risks of these endpoints were reduced by 37 percent (p=0.03) and 44 percent (p=0.07), respectively.
“The risk of the key composite outcome of MACE, MALE or major amputation was significantly reduced by 31 percent [p=0.0003] with rivaroxaban plus aspirin vs aspirin alone,” reported Anand. “The risk reduction was not significant for rivaroxaban monotherapy [HR, 0.84; p=0.08].”
In the PAD cohort, rivaroxaban plus aspirin was associated with increased major bleeding vs aspirin alone (3.1 vs 1.9 percent; HR, 1.61; p=0.009). Major bleeding was also increased with rivaroxaban monotherapy given at the higher dose (3.2 percent; HR, 1.68 vs aspirin alone; p=0.004). “However, no increase in fatal bleeding, intracranial haemorrhage or bleeding in other critical organs was observed,” said Anand.
“The net clinical benefit of rivaroxaban plus aspirin over aspirin alone is significant [HR, 0.72; p=0.0008] in the PAD cohort of COMPASS. The benefit is consistent in patients with symptomatic PAD, PAD of lower extremities, or carotid artery disease,” she noted.
“The results of COMPASS PAD suggest that rivaroxaban plus aspirin is a new treatment alternative in patients with PAD. Until now, we have only had aspirin, which is modestly effective,” commented discussant Professor Lars Wallentin of Uppsala Clinical Research Centre, Uppsala University, Sweden.
“However, the optimal timing of starting patients on this combination therapy remains unknown, because transition from post-acute coronary syndrome treatment was avoided in the trial,” he continued. “It is also uncertain whether rivaroxaban or aspirin should be discontinued in the event of bleeding.”