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Rivaroxaban with aspirin effective in people with stable PAD or CAD

Rivaroxaban with aspirin effective in people with stable PAD or CAD

Publication date: Thursday, 16 August 2018

The study included 7470 participants recruited from 558 centres across 33 countries, including the UK. Participants either had a history of PAD of the lower extremities or carotid artery disease or coronary artery disease. After a 30 day run-in period (during which participants took aspirin 100 mg daily), participants were randomised to receive either oral rivaroxaban 2.5 mg twice daily plus aspirin 100 mg once daily (n=2492), rivaroxaban 5 mg twice daily (n=2474), or aspirin 100 mg once daily (n=2504). The median duration of follow-up was 21 months. The characteristics of those with PAD were reported to be well balanced between the 3 treatment groups.

The primary outcome (the composite of cardiovascular death, myocardial infarction or stroke) was 5% in the rivaroxaban plus aspirin group compared with 7% of the aspirin group. There was no statistically significant difference reported in the individual outcomes of myocardial infarction, cardiovascular death or death between the two groups although stroke rate was higher in the aspirin alone group (2% vs 1%)

Fewer participants in the rivaroxaban plus aspirin group compared with the aspirin alone group had major adverse limb events or major amputations. There was no statistically significant difference between the 2 groups for chronic limb ischaemia and no statistically significant difference for major amputations between the 2 groups.    

The primary safety outcome was major bleeding. There was a statistically significant increase in major bleeding in the combination group compared with the aspirin alone group (3%) vs 2%, and a similar finding in the rivaroxaban alone group compared with aspirin alone. The most common site of bleeding for all groups was gastrointestinal.

 

 

Key results from the study

  • The combination therapy group had fewer major adverse limb events (1% vs 2%, HR 0.54, 95% CI 0.35 to 0.84, p=0.0054) and major amputations (<1% vs 1%, HR 0.30, 95% CI 0.11 to 0.80, p=0.011).
  • Primary outcome (CV death, MI or stroke) seen in 5% of rivaroxaban plus aspirin group compared with 7% of the aspirin group (HR 0.72, 95% CI 0.57 to 0.90, p=0·0047).
  • 1% of patients on the combination therapy had a stroke compared with 2% of patients on aspirin alone (HR 0.54, 95% CI 0.33 to 0.87).
  • A statistically significant increase in major bleeding was seen in the low-dose rivaroxaban plus aspirin group compared with the aspirin alone group (3% vs 2%, HR 1.61, 95% CI 1.12 to 2.31, p=0.0089). A similar finding was reported in participants in the rivaroxaban alone group when compared with aspirin alone (3% vs 2%, HR 1.68, 95% CI 1.17 to 2.40, p=0.0043).
  • The most common site of bleeding for all groups was gastrointestinal.

Rivaroxaban 2.5 mg twice daily is not licensed for the prevention of occlusive vascular events in people with PAD or CAD. Clopidogrel is the standard antiplatelet used in PAD and cerebrovascular disease and by not having a comparison with clopidogrel in the study, the relevance of the results to UK practice is limited at present. NICE has issued guidance on ‘Clopidogrel and modified-release dipyridamole for the prevention of occlusive vascular events’ https://www.nice.org.uk/guidance/ta210 and ‘Peripheral arterial disease: diagnosis and management’ https://www.nice.org.uk/guidance/cg147.

The NICE guideline on PAD recommends that all people with PAD are offered information, advice, support and treatment regarding the secondary prevention of cardiovascular disease, in line with published NICE guidance on myocardial infarction: cardiac rehabilitation and prevention of further cardiovascular disease.

ACTION

This study provides some interesting results, but rivaroxaban does not yet have a licence for preventing occlusive vascular events in PAD or CAD. The study does not have a comparison with clopidogrel and so its relevance to current UK practice is limited at present.

Anand S, Bosch J, Eikleboom J et al. Rivaroxaban with or without aspirin in patients with stable peripheral or carotid artery disease: an international, randomised, double-blind, placebo-controlled trial. The Lancet 2018;391:219–29.  https://www.sciencedirect.com/science/article/pii/S0140673617324091?via%3Dihub

Topics covered:
Category: Evidence in Practice
Edition: Volume 1 Number 1 PCCJ Online 2004

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