European experiences reviewed

Insights from the world of cardiology

Background

The novel oral anticoagulant (NOAC) agents (dabigatran, rivaroxaban, apixaban) have had a disproportionally poor uptake since their respective launches and National Institute for Health and Care Excellence (NICE) Technology Appraisal in the UK between 2012 and 2013 for their use in stroke prevention in patients with non-valvular atrial fibrillation (NVAF), when compared with our European counterparts; particularly Germany, Holland and France. In the original NICE economic analyses for the NOACs there was a calculated uptake of approximately 20% in the first year,¹ the figure currently runs at <8% with many area’s significantly lower.²

Why the delay in uptake in the UK?

The use of anticoagulation in atrial fibrillation (AF) in the UK has been disproportionately poor for many years. Failure to recognise the benefits of anticoagulation has been reinforced historically through the failure to financially reward vitamin K anatgonist (VKA) prescribing through the Quality and Outcomes Framework (QOF). There is a paradigm shift required in the understanding within UK general practice/general internal medicine to appreciate that anticoagulation should be a default treatment for all but the very-low-risk patients (CHADSVASc <1) with AF. Once this message is clearly accepted then movement towards anticoagulation agents, specifically those with good safety profiles (NOACs) may be easier.

There are many challenges involved in the uptake of new agents, particularly so in the UK. As a medical society we are proud of our cautious response to potentially hazardous innovations.

The funding of healthcare in the UK is unique. The National Health Service (NHS) reforms in 2012 placed the responsibility for continued prescribing firmly with commissioning clinical commissioning groups (CCGs). This may negatively incentivise high-cost healthcare reform. The lack of a joint social and health budget places all the cost of healthcare interventions upon a commissioning CCG; whom in themselves would not see a benefit from the overall saving to both social and healthcare of an innovation.

Summary

The significant experience that European prescribers report from the use of the NOACs, and in particular rivaroxaban, is most encouraging. These reports should reassure UK prescribers of the safety profile and low bleeding incidence in real-world populations.

Many of the concerns listed by European colleagues regarding the prescription of NOACs are universal and extend to the UK. A real fear of the complications from prescriptions without the reassurance of compliance monitoring that occurs with VKA is often cited, as is the lack of an antidote currently.

Key differences of NOACs

There are no head-to-head studies between the NOACs and, therefore, comparisons between the agents are very difficult. The published meta-analyses are helpful.⁴ In real-world prescribing, however, rivaroxaban has a once-daily formulation, safety data in renal impairment and published experience in its use with co-existent coronary disease in acute coronary syndromes.^5,6 Familiarity of prescribing rivaroxaban within its other licenced indications may help build confidence in its use in AF.

Secondary care role

There is a key role for secondary care in the UK to improve the management of stroke prevention in patients with AF. There is a real need for continued education to raise awareness of the published evidence of anticoagulation efficacy versus antiplatelet therapy, and the comparable efficacy and safety profiles of the NOAC agents compared to VKAs. The cost-effectiveness modelling needs to be communicated to commissioning medicines management agencies focusing upon previously excluded benefits: e.g. reduction in hospitalisation costs and ongoing care costs for those patients no longer at risk of major haemorrhage.

References

1. ABPI-SAFI. NOACs: Innovation in anticoagulation. Optimising the prevention of AF-related stroke. London: ABPI, March 2014.
2. http://www.england.nhs.uk/ourwork/pe/mo-dash/ [accessed July 2014].
3. Capodanno D, Capranzano P, Giacchi G et al. Novel oral anticoagulants versus warfarin in non- valvular atrial fibrillation: a meta-analysis of 50,578 patients. Int J Cardiol 2013;167:1237–41. http://dx.doi.org/10.1016/j.ijcard.2012.03.148
4. Dentali F, Riva N, Crowther M et al. Efficacy and safety of the novel oral anticoagulants in atrial fibrillation: a systematic review and meta-analysis of the literature. Circulation 2012;126:2381–91. http://dx.doi.org/10.1161/CIRCULATIONAHA.112.115410
5. The EINSTEIN Investigators. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010;363:2499–510. http://dx.doi.org/10.1056/NEJMoa1007903
6. Mega JL, Braunwald E, Wiviott SD et al. Rivaroxaban in patients with a recent acute coronary syndrome. New Engl J Med 2012;366:1–11. http://dx.doi.org/10.1056/NEJMoa1112277