Aspirin plus Rivaroxaban in stable CAD
Aspirin plus Rivaroxaban in stable Coronary Artery Disease (CAD)
- Low dose rivaroxaban (2.5mg twice daily) is now licensed in combination with aspirin for the prevention of atherothrombotic events in adult patients with coronary artery disease (CAD) or symptomatic peripheral artery disease (PAD) at high risk of ischaemic events.
- Rivaroxaban co-administered with aspirin for the prevention of artherothrombotic events in adults is restricted to initiation by, or on the advice of a consultant only in patients with stable CAD that do not require dual antiplatelet therapy.
- Rivaroxaban in combination with aspirin for the prevention of atherothrombotic events in patients with PAD alone was not considered by SMC and the use in this setting is non-Formulary.
- The GGC Heart MCN reviewed the results of the COMPASS1 study (summary below) and subsequent SMC advice and, in view of the small absolute differences and absence of convincing net clinical benefit, there are no plans to introduce the routine use of the combination of rivaroxaban and low-dose aspirin. The prescribing decision for individual patients is at the discretion of a consultant cardiologist.
Summary of trial evidence
The recent COMPASS1 study demonstrated a significantly lower rate of the composite outcome of myocardial infarction (MI), stroke and cardiovascular death with the addition of rivaroxaban 2.5 mg twice daily to low-dose aspirin in a study population of patients with stable cardiovascular disease, mostly coronary artery disease (CAD). Absolute reductions were small at around 1.3-1.4%. The differences were mainly due to reductions in stroke (0.7%) and cardiovascular death (0.5%), with no reduction in rates of MI.
Addition of rivaroxaban to low-dose aspirin was associated with an increased incidence of major bleeding with similar absolute differences of 1.3% in patients with CAD, mainly due to an increased rate of hospital admissions with non-fatal gastrointestinal bleeding.
A net clinical benefit of 1.3% was described in the study, defined as an outcome of MI, stroke, cardiovascular death, fatal or symptomatic bleed into a critical organ, but excluded bleeding that led to presentation at hospital, admission or re-operation post-surgery. However, if all major bleeding is included then there is little or no net clinical benefit remaining.
1. Connolly SJ, Eikelboom JW, Bosch J, et al. Rivaroxaban with or without aspirin in patients with stable coronary artery disease: an international, randomised, double-blind, placebo-controlled trial. Lancet 2018; 391: 205-18.
Published 25/03/19. Updated 16/12/19. Medicines Update blogs are correct at the time of publication.