Cost Effectiveness and Clinical Efficacy of Pradaxa® (Dabigatran Etexilate) versus Rivaroxaban Analysed

- Indirect comparison based on the RE-LY® trial (for dabigatran etexilate) and the Rocket AF trial (for rivaroxaban) suggests advantages of Pradaxa® in stroke prevention in patients with atrial fibrillation

Ingelheim, Germany, Friday 24th August 2012 – In the absence of a head-to-head study, a comprehensive analysis published in Thrombosis and Hemostasis,¹ looks into the efficacy and cost-effectiveness of Pradaxa® for stroke prevention in patients with non-valvular atrial fibrillation in an indirect comparison to rivaroxaban. The analysis, based on two large scale   trials including more than 32.000 patients combined, suggests that patients treated with Pradaxa® may have lower rates of ischaemic stroke and intracranial haemorrhage (ICH), and also accumulate lower costs from acute care and long-term follow-up over their lifetime than  patients treated with rivaroxaban.¹
The authors conducted a formal indirect treatment comparison between Pradaxa® and rivaroxaban (according to the Markov model).
The analysis has to be viewed in light of the absence of a head-to-head study. The current interest in healtheconomic aspects of new treatments may encourage further scientific assessments to confirm the findings. Boehringer Ingelheim would endorse and support further investigation.
In the analysis the authors conclude:¹

• Pradaxa® may provide a lower risk of stroke (RR=0.62; 95% CI 0.45-0.87) than rivaroxaban
• Pradaxa® may provide a lower risk of intracranial haemorrhage (ICH) (RR=0.38; 95% CI 0.21-0.67) than rivaroxaban

Looking at events per 100 patient-years, the model predicts that over a lifetime horizon, AF patients may experience¹

• Considerably fewer ICH with Pradaxa® than with rivaroxaban (0.33 vs. 0.71)
• Less ischaemic strokes with Pradaxa® than with rivaroxaban (3.40 vs. 3.96)
• More quality-of-life-years with Pra-daxa® than with rivaroxaban (6.17 vs. 6.01)

When assessing the costs of care, the analysis implies that patients treated with Pradaxa® incur lower costs of acute care and long term follow-up per patient, which, according to the authors, more than offset differences in drug costs.¹ The study shows consistent conclusions to previous analysis evaluating novel oral anticoagulant treatments in the Canadian market.²
The indirect comparison model is based on data from ROCKET AF³ where patients were treated with rivaroxaban and Pradaxa® clinical event rates as observed in the safety-on-treatment population⁴ in RE-LY®, a prospective,  randomized, open-label trial with blinded endpoint evaluation, comparing two fixed doses of the oral direct thrombin inhibitor da-bigatran etexilate (110mg and 150mg bid) each administered in a blinded manner, with open label warfarin.^5,6 The Pradaxa® data were adjusted mainly to reflect the higher level of  warfarin control in RE-LY®) (the mean TTR (TTR = time in therapeutic range) was 64% in RELY® and 55% in ROCKET-AF) and simulated dosing  corresponding to the approved Canadian treatment algorithm⁷ for Pradaxa.
Dr Anuraag Kansal a research scientist in Health Economics, United BioSource Corporation, headquartered in the US said, “As more anticoagulation therapies become available, there is a need to understand the clinical and economic differences between new therapies. This research tells us that the benefits of da-bigatran etexilate accrue steadily over time and that the novel oral anticoagulant continues to offer effective stroke protection for patients living with AF.”

NOTES TO THE EDITORS
Stroke Prevention in Atrial Fibrillation
AF is the most common sustained heart rhythm condition⁸, with one in four adults over the age of 40⁹ developing the condition in their lifetime. People with AF are more likely to experience blood clots, which increases the risk of stroke by five-fold.^9,10 Up to three million people worldwide suffer strokes related to AF each year.^11-14 Strokes due to AF tend to be severe, with an increased likelihood of death (20%), and disability (60%).¹⁵
Ischaemic strokes are the most common type of AF-related stroke, accounting for 92% of strokes experienced by AF patients and frequently leading to severe debilitation.^16-20 Appropriate anticoagulation therapy can help to prevent many types of AF-related strokes and improve overall patient outcomes.²¹
Worldwide, AF is an extremely costly public health problem, with treatment costs equating to $6.65 billion in the US and over €6.2 billion across Europe each year.^21,22 Given AF-related strokes tend to be more severe, this results in higher direct medical patient costs  annually.²³ The total societal burden of AF-   related stroke reaches €13.5 billion per year in the European Union alone.²³

• About the dabigatran etexilate clinical trial programme
• Boehringer Ingelheim’s clinical trial programme to evaluate the efficacy and safety of dabigatran etexilate encompasses studies in:
• Primary prevention of venous thromboembolism (VTE) in patients under-going elective total hip and knee replacement surgery
• Treatment of acute VTE
• Secondary prevention of VTE
• Stroke prevention in AF
• Prevention of thromboembolism after heart valve replacement.

Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 145 affiliates and more than 44,000 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel medications of high the-rapeutic value for human and veterinary medicine.
As a central element of its culture, Boehringer Ingelheim pledges to act socially responsible. Involvement in social projects, caring for employees and their families, and providing equal opportunities for all employees form the foundation of the global operations. Mutual cooperation and respect, as well as environmental protection and sustainability are intrinsic factors in all of Boehringer Ingelheim’s endeavours.
In 2011, Boehringer Ingelheim achieved net sales of about 13.2 billion euro. R&D expenditure in the business area Prescription Medicines corresponds to 23.5% of its net sales.
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References
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²Canadian Agency for Drugs and Technology in Health. New Oral Anticoagulants for the Prevention of Thromboembolic Events in Patients with Atrial Fibrillation. April 9, 2012. Available at http://www.cadth.ca/media/pdf/NOAC_Therapeutic_Review_final_report.pdf
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