Physicians' Academy for Cardiovascular Education

Rivaroxaban plus aspirin, lowers CV and major adverse limb events, but increases bleeding in patients with stable CAD and PAD

Literature -

Rivaroxaban with or without aspirin in patients with stable coronary artery disease: an international, randomised, double-blind, placebo-controlled trial

Connolly SJ, Eikelboom JW, Bosch J, et al. The Lancet 2018;391:205-218

Rivaroxaban with or without aspirin in patients with stable peripheral or carotid artery disease: an international, randomised, double-blind, placebo-controlled trial

Anand SS, Bosch J, Eikelboom JW, et al. The Lancet 2018;391:219-229

Background

Use of anticoagulant therapy, an antiplatelet agent or a combination of these two has given mixed results in the outcomes of patients with stable coronary artery disease (CAD) and peripheral artery disease (PAD). The factor Xa inhibitor apixaban, in combination with antiplatelet therapy, showed no reduction in thrombotic events in ACS patients compared to placebo, whereas fatal and intracranial bleeding were increased [1]. In contrast, in the ATLAS 2 trial, rivaroxaban with aspirin reduced the risk of major ischemic events, the composite outcome of stroke, MI and CV death and overall mortality in ACS patients, although rivaroxaban alone (5 mg twice a day) increased major, intracranial and fatal bleeding [2].

The Cardiovascular Outcomes for People using Anticoagulation Strategies (COMPASS) trial [3,4] was a multicenter, randomized, double-blind, placebo-controlled trial, which enrolled 27395 patients with CAD or PAD and evaluated the effect of a factor Xa inhibitor on top of antiplatelet therapy. Patients with CAD (n=24824, median follow-up: 1.95 years) were required to be ≥65 years with documented atherosclerosis, revascularization or 2 of the following risk factors: smoking, diabetes, eGFR<60 mL/min, HF or non-lacunar stroke. Patients eligible for the PAD cohort (n=7470, median follow-up: 21 months) had PAD of the lower extremities, of the carotid arteries, or CAD with an ankle brachial index of <0.90.

After a run-in period of 30 days, patients were randomized to receive low-dose rivaroxaban (2.5 mg twice a day) plus aspirin (100 mg once a day), rivaroxaban alone (5 mg twice a day) or aspirin alone (100 mg once a day). The primary outcome was a composite consisting of stroke, MI, or CV death. The primary PAD outcome was major adverse limb events including major amputations. There were three secondary outcomes: a composite of coronary heart disease (CHD) death, MI, ischemic stroke, or acute limb ischemia; occurrence of MI, ischemic stroke, CV death, or acute limb ischemia; and overall mortality.

Main results

Patients with stable CAD (Connolly et al.)

Patients with PAD (Anand et al.)

Conclusion

Addition of low-dose rivaroxaban to aspirin reduces major CV events and limb events in patients with stable CAD or PAD. However, there is also an increased risk for bleeding, although few critical or fatal bleedings occurred after dual treatment. Therefore, low-dose rivaroxaban in combination with aspirin can be of clinical benefit in a broad group of patients with CAD and PAD.

References

Show references

Find Connolly et al online at The Lancet 2018 Find Anand et al online at The Lancet 2018