Pradaxa® (dabigatran etexilate) receives final NICE recommendation for stroke prevention in atrial fibrillation in the UK

Professor Gregory Lip, Consultant Cardiologist & Professor of Cardiovascular Medicine, University of Birmingham Centre for Cardiovascular Sciences, Birmingham, United Kingdom

On 15 March, the National Institute for Health and Clinical Excellence (NICE) issued final guidance recommending the novel oral anticoagulant, Pradaxa® (dabigatran etexilate) ² as a cost-effective option for the prevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation (AF) and one or more risk factors. ¹

This landmark decision means Pradaxa® must now be made available for use by the UK National Health Service (NHS) and that patients have the right to receive it if clinicians deem it clinically appropriate.

Professor Gregory Lip, Consultant Cardiologist & Professor of Cardiovascular Medicine, University of Birmingham Centre for Cardiovascular Sciences, Birmingham, United Kingdom

Professor Gregory Lip, Consultant Cardiologist & Professor of Cardiovascular Medicine, University of Birmingham Centre for Cardiovascular Sciences, Birmingham, United Kingdom commented, “The final NICE recommendation of dabigatran etexilate in the UK represents a major advance in the treatment of this condition. NICE estimates that only half of eligible patients receive warfarin due to the treatment having many limitations such as the need for regular monitoring and various food-drug and drug-drug interactions. This means that many AF patients are not currently taking an anticoagulant and may therefore be at an increased risk of stroke. The approval of dabigatran etexilate has the potential to significantly reduce the risk of stroke in patients with AF who are eligible for anticoagulation therapy.”

AF affects around 1% of the total population worldwide with approximately 1.2 million people diagnosed with AF in the UK alone, ⁴ of which 77% are eligible for treatment with an anticoagulant. ⁵ AF increases the risk of stroke by five-fold, ^3,6 with AF-related stroke tending to be severe and associated with a likelihood of death (20%) and disability (60%). ⁷

Pradaxa® is now the only novel oral anticoagulant recommended for use in the UK for the prevention of stroke in AF, offering the first treatment alternative to current standard of care warfarin. This is an important landmark given that the use of Pradaxa® 150mg twice daily has the potential to prevent 470 more strokes per 100,000 patients every year compared to warfarin. ^8-11

The final NICE guidance of Pradaxa® for stroke prevention in AF is based on the groundbreaking results from RE-LY®, one of the largest studies ever conducted in AF including over 18,000 patients. RE-LY® was a PROBE (prospective, randomized, open-label with blinded endpoint evaluation) trial, comparing two fixed doses of the oral direct thrombin inhibitor dabigatran etexilate (110mg and 150mg bid) each administered in a blinded manner, with open label warfarin. ^9,10,12

Pradaxa® 150mg bid is the only novel oral anticoagulant proven superior to well-controlled warfarin (median TTR 67% 12) in significantly reducing both ischaemic and haemorrhagic stroke in patients with non-valvular AF. 9,10 Pradaxa® 150mg bid reduced the risk of stroke and systemic embolism by 35% while also significantly lowering the risk of life-threatening and intracranial bleeding, compared to well-controlled warfarin. 9,10 The novel treatment also does not require frequent coagulation monitoring or routine dose adjustment and has no known dietary restrictions, which can be associated with warfarin.

Pradaxa® is also approved in the UK (by NICE) for the primary prevention of venous thromboembolic events (blood clots) in adults who have undergone elective total hip or elective total knee replacement surgery. ¹³

References

1. NICE final guidance Accessed March 2012.
2. Pradaxa®, Summary of Product Characteristics, 2011. Europe.
3. Lloyd-Jones DM, Wang TJ, Leip EP, et al. Lifetime risk for development of atrial fibrillation: the Framingham Heart Study. Circulation 2004; 110:1042-6.
4. Atrial Fibrillation Association. February 2011. Available at http:// http://www.atrialfibrillation.org.uk/ Accessed March 2012.
5. NICE Assumptions used in estimating a population benchmark http://www.nice.org.uk/usingguidance/commissioningguides/anticoagulationtherapyservice/popbench.jsp / Accessed March 2012.
6. Fuster V, Rydn LE, Cannom DS, et al. ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation – executive summary. Circulation 2006; 114:700-52.
7. Lin HJ, Wolf PA, Kelly-Hayes M, et al. Stroke severity in atrial fibrillation: the Framingham study. Stroke 1996; 27:1760-4.
8. Atrial fibrillation investigators. Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation. Ann Intern Med 1994; 154: 1449-57.
9. Connolly SJ, et al. Dabigatran versus Warfarin in Patients with Atrial Fibrillation. N Engl J Med 2009; 361:1139-51.
10. Connolly SJ, et al. Newly identified events in the RE-LY® trial. N Engl J Med 2010;363(19): 1875-6.
11. Hart RG, et al. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have non-valvular atrial fibrillation. Ann Intern Med 2007 146:857-867.
12. FDA Advisory Committee Briefing Document, September 2010,http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisory Committee/UCM226009.pdf.
13. NICE technology appraisal guidance. Dabigatran etexilate for the prevention of venous thromboembolism after hip or knee replacement surgery in adults. September 2008. Available at http://guidance.nice.org.uk/TA157/Guidance/pdf/English/ Accessed March 2012.