NCPE Rejects Xarelto for Reimbursement in AF Indication in Ireland

The NCPE has announced its decision to reject the reimbursement of Xarelto (rivaroxaban; Bayer, Germany) for the prevention of stroke in atrial fibrillation (AF). The decision was issued after a review of over four months, initiated on 11 November 2011. The NCPE concluded that Xarelto is "not cost-effective for this indication at the submitted price".

The full guidance (available here) specifically considered the use of Xarelto for the prevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation with one or more risk factors, such as congestive heart failure, hypertension, age >75 years, diabetes mellitus, prior stroke, or transient ischaemic attack.

Bayer's base-case analysis compared rivaroxaban 20mg once daily (followed by aspirin once rivaroxaban was discontinued) with warfarin (followed by aspirin once discontinued) using a Markov model to demonstrate cost effectiveness. The analysis relied primarily on clinical data from the ROCKET AF trial, as well as published literature used to extrapolate beyond the trial period to life (30 years).

The study found that there was no significant difference in the rates of major and non-major clinically relevant bleeding with rivaroxaban (14.9% per year) in comparison with warfarin (14.5% per year; HR=1.03; 95% CI 0.96, 1.11; p=0.44). Rivaroxaban performed better in terms of side effects though; there were significant reductions in intracranial haemorrhage (0.5% compared with 0.7%; p =0.02) and fatal bleeding (0.2% compared with 0.5%; p = 0.003) in the rivaroxaban group.

The incremental cost-effectiveness ratio (ICER) for rivaroxaban versus warfarin was EUR22,663 (USD29,628) per quality-adjusted life year (QALY) in the intention-to-treat (ITT) population. For the ITT population, there was a 40–64% probability that rivaroxaban will be cost effective at the threshold range of EUR20,000–30,000 per QALY. For the wider safety on treatment, the ICERs were EUR15,990 per QALY at General Medical Services Scheme prices, and EUR28,989 per QALY at Drug Payment Scheme (DPS) prices, with 60–80% probability that rivaroxaban will be cost effective at the threshold range of EUR20,000–30,000 per QALY. If DPS prices are applied, the ICER increases to EUR39,330 per QALY, according to the guidance.

Outlook and Implications

The NCPE concluded that the drug is not cost effective at the submitted price, resulting in a rejection of reimbursement for the AF indication. The decision is not surprising, considering that Bayer's clinical data was geared towards supporting a non-inferiority claim, rather than a superiority claim, versus a well established and now off-patent comparator. Although safety outcomes were slightly better for rivaroxaban, the difference was not substantial enough to justify higher expenditure. The budget impact of rivaroxaban for the AF indication is EUR27.8 million net and EUR42.3 million cumulative, according to the manufacturer's estimates.

Despite this negative reimbursement decision, Bayer will still have access to reimbursement for Xarelto in Ireland for a different indication—the treatment of deep vein thrombosis (DVT) and prevention of recurrent DVT and pulmonary embolism following acute DVT in adults. The NCPE issued positive guidance for the latter in March (see Ireland: 8 March 2012: NCPE Issues Positive Guidance for Xarelto in Ireland).