The National Institute for Health and Care Excellence (NICE) in the UK has published a positive draft final appraisal determination recommending the use of rivaroxaban (brand name Xarelto, Bayer) by the National Health Service (NHS) in England. The NICE recommendation sets out a dose of 2.5mg twice daily, combined with 75–100mg aspirin once daily, as an option for preventing atherothrombotic events in adult patients with coronary artery disease (CAD) or symptomatic peripheral arterial disease (PAD) who are at high risk of ischaemic events.
Publication of this NICE draft is based on evidence from the COMPASS study, the largest Phase III study with rivaroxaban (27,395 patients). This study showed that rivaroxaban vascular dose, 2.5mg twice daily combined with aspirin 100mg once daily, statistically significantly reduced the risk of the composite of cardiovascular (CV) death, stroke or myocardial infarction (major adverse cardiovascular events; MACE) by 24% (relative risk reduction, ARR: 1.3%) compared with aspirin 100mg once daily alone amongst patients with stable atherosclerotic vascular disease (379 patients [4.1%] vs. 496 patients [5.4%]; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.86; p<0.001).
In the COMPASS trial, for patients with stable CAD, addition of rivaroxaban 2.5mg twice daily with aspirin 100mg once daily lowered major adverse cardiovascular events compared with aspirin once daily (347 [4%] of 8313 vs. 460 [6%] of 8261; HR 0·74, 95% CI 0·65–0·86, p<0·0001). Moreover, patients with PAD who received rivaroxaban 2.5mg twice daily combined with aspirin 100mg once daily, also had fewer major cardiovascular events compared with the aspirin 100mg once daily alone group (126 [5%] of 2492 vs. 174 [7%] of 2504; HR 0·72, 95% CI 0·57-0·90, p=0·0047).
Rivaroxaban is an anticoagulant that targets Factor Xa, an enzyme which acts at a key point in the blood clotting process, inhibiting its ability to generate thrombin. NICE are recommending use of rivaroxaban as part of a dual pathway approach (in combination with aspirin) to prevent atherothrombotic events in patients who are at high risk of such events. Coronary artery disease patients who are at high risk of ischaemic events are defined by NICE as those aged 65 or over, patients with atherosclerosis in at least two vascular territories, or those presenting risk factors such as smoking, diabetes, kidney dysfunction, heart failure or a history of stroke.
Derek Connolly, COMPASS trialist, consultant interventional cardiologist and honorary senior clinical lecturer at Birmingham City Hospital (Birmingham, UK) said: “Cardiovascular disease remains the biggest cause of years of life lost in the UK. There have been few recent major new advances in the medical management of patients with CAD and PAD to protect them against strokes or heart attacks.
“The COMPASS trial showed that adding rivaroxaban vascular dose to low-dose aspirin significantly reduced vascular events. The large reduction in events [such as strokes], outweighed the increase in major bleeding events seen. Conducted in more than 30 countries, including the UK, COMPASS was one of the largest ever trials of oral anti-thrombotic therapy providing robust results, overall, and particularly for key patient subgroups at high-risk of recurrent events such as those with renal dysfunction or stable ‘mild’ heart failure.”
“Rivaroxaban vascular dose in combination with aspirin is the first treatment of its kind for this patient population and this recommendation from NICE provides clinicians with an important additional option for treating patients at risk of major adverse cardiac events such as cardiovascular death, stroke or myocardial infarction.”
Lars Bruening, CEO Bayer UK & Ireland, said: “Bayer has a long and successful heritage in cardiology. The NICE recommendation provides those with high risk CAD and symptomatic PAD with an effective treatment option that will provide additional tailored protection from atherothrombosis. Ten years on from the introduction of rivaroxaban into the UK we are continuing to see the enduring impact that it has on patients treated across its licensed indications—and now this new patient population with previous unmet needs can be considered.”
Publication of the NICE draft for rivaroxaban follows approval by the European Commission (EC) in August 2018 for the regimen of rivaroxaban 2.5mg twice daily plus aspirin 75–100mg once daily for the prevention of atherothrombotic events in adult patients with CAD or symptomatic PAD at high risk of ischaemic events. Rivaroxaban is the most broadly indicated NOAC worldwide. It is approved in the UK for:
- The prevention of stroke and systemic embolism in adult patients with non-valvular AF with one or more risk factors
- The treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) and prevention of recurrent DVT and PE in adults
- The prevention of venous thromboembolism (VTE) in adult patients undergoing elective hip or knee replacement surgery
- The prevention of atherothrombotic events in adult patients after an acute coronary syndrome (ACS) with elevated cardiac biomarkers, co-administered with aspirin alone or with aspirin plus clopidogrel or ticlopidine
- 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