Rivaroxaban for Preventing Atherothrombotic Events in People with Acute Coronary Syndrome and Elevated Cardiac Biomarkers: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

As part of its Single Technology Appraisal process, the National Institute for Health and Care Excellence (NICE) invited the company that manufactures rivaroxaban (Xarelto, Bayer) to submit evidence of the clinical and cost effectiveness of rivaroxaban for the prevention of adverse outcomes in patients after the acute management of acute coronary syndrome (ACS). The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a critical review of the evidence for the clinical and cost effectiveness of the technology, based upon the company's submission to NICE. The evidence was derived mainly from a randomised, double-blind, phase III, placebo-controlled trial of rivaroxaban (either 2.5 or 5 mg twice daily) in patients with recent ACS [unstable angina, non-ST segment elevation myocardial infarction (NSTEMI) or ST segment elevation myocardial infarction (STEMI)]. In addition, all patients received antiplatelet therapy [aspirin alone or aspirin and a thienopyridine either as clopidogrel (approximately 99 %) or ticlopidine (approximately 1 %) according to national or local guidelines]. The higher dose of rivaroxaban (5 mg twice daily) did not form part of the marketing authorisation. A post hoc subgroup analysis of the licensed patients who had ACS with elevated cardiac biomarkers (that is, patients with STEMI and NSTEMI) without prior stroke or transient ischaemic stroke showed that compared with standard care, the addition of rivaroxaban (2.5 mg twice daily) to existing antiplatelet therapy reduced the composite endpoint of cardiovascular mortality, myocardial infarction or stroke, but increased the risk of major bleeding and intracranial haemorrhage. However, there were a number of limitations in the evidence base that warrant caution in its interpretation. In particular, the evidence may be confounded because of the post hoc subgroup analysis, modified intention-to-treat analyses, high dropout rates and missing vital status data. Results from the company's economic evaluation showed that the deterministic incremental cost-effectiveness ratio (ICER) for rivaroxaban in combination with aspirin plus clopidogrel or with aspirin alone compared with aspirin plus clopidogrel or aspirin alone was £6203 per quality-adjusted life-year (QALY) gained. In contrast, the ERG's preferred base case estimate was £5622 per QALY gained. The ICER did not rise above £10,000 per QALY gained in any of the sensitivity analyses undertaken by the ERG, although the inflexibility of the company's economic model precluded the ERG from formally undertaking all desired exploratory analyses. As such, only a crude exploration of the impact of additional bleeding events could be undertaken. The NICE Appraisal Committee concluded that the ICERs presented were all within the range that could be considered cost effective and that the results of the ERG's exploratory sensitivity and scenario analyses suggested that the ICER was unlikely to increase to the extent that it would become unacceptable. The Appraisal Committee therefore concluded that rivaroxaban in combination with aspirin plus clopidogrel, or with aspirin alone, was a cost-effective use of National Health Service (NHS) resources for preventing atherothrombotic events in people with ACS and elevated cardiac biomarkers.