A new economic analysis, published  online in Thrombosis and Haemostasis, suggested that Boehringer Ingelheim's novel oral direct thrombin inhibitor dabigatran etexilate is cost-effective compared to current treatment options, particularly in real-world clinical practice.

This cost-effectiveness was driven by superior prevention of ischemic stroke alongside a reduction in devastating intracranial bleeding by dabigatran etexilate compared to well-controlled warfarin, in patients with Atrial Fibrillation (AF). When dabigatran etexilate was compared against current care, including 'real-world' warfarin, it saved 4,783 Canadian dollars (CAD) on average per patient for prevention of events, such as stroke, and the subsequent associated follow-on costs.

Dr Stuart Connolly, principal investigator of the RE-LY trial and co-author of the economic evaluation commented, “We want to do the best for patients and dabigatran is the medically preferred treatment for stroke prevention. From the analyses reported today, we now know that it is cost-effective too - good value to our scarce healthcare budget.”

The economic model evaluated patients in Canada who were treated with dabigatran etexilate compared to those treated with warfarin in both 'trial-like' conditions (using the RE-LY trial results) and in a “real-world” clinical practice setting, where patients either received warfarin, aspirin or no treatment. In the “real-world” clinical practice setting, dabigatran etexilate was shown to be particularly cost-effective compared to current care.

In a 'real-world' setting, many patients are not being treated adequately for stroke prevention. This is primarily due to the well-documented limitations of warfarin. Dabigatran etexilate also does not require routine coagulation monitoring or dose adjustments, is not affected by food and has a low potential for drug-drug interactions.

The model showed that over a lifetime, dabigatran etexilate treated AF patients experienced fewer ischemic strokes and intracranial bleeds compared to current care, which largely offsets the acquisition cost of dabigatran etexilate compared to current treatment options.

Patients treated with dabigatran etexilate suffered less ischemic strokes than patients treated with current care (“trial-like” warfarin or “real-world” warfarin, aspirin or no treatment).

Patients treated with dabigatran etexilate had less than half the number of intracranial bleeds compared to current care (0.49 dabigatran etexilate vs. 1.13 warfarin vs. 1.05 2 “real-world” prescribing). Overall, dabigatran etexilate was cost-effective, especially when compared to ‘real world’ care. The Incremental Cost-Effectiveness Ratio (ICER) of dabigatran etexilate was $10,440/Quality Adjusted Life Year (QALY) versus “trial-like” warfarin and $3,962/QALY versus “real-world” warfarin, aspirin or no treatment).

Willingness to pay threshold for additional health benefits is an important element in healthcare decision makers' assessment of whether new therapies represent good value for money. In Canada, a willingness to pay threshold of CAD 30,000 per QALY-gained is considered acceptable while being conservative.1 The results for dabigatran etexilate fall well below this threshold.

AF is a leading cause of stroke, which in turn is associated with higher mortality and costlier hospital stays than stroke in patients without AF.  Additionally AF is associated with an increased risk of systemic embolism which may result in major damage to limbs and organs (e.g. embolism (blood clot) to the renal artery). While the economic cost of a stroke can be exorbitant, often entailing years of rehabilitation and supervised care, the emotional impact on patients and their families is also devastating.

This economic study modelled AF patients at risk of stroke while tracking clinical events (primary and recurrent ischemic strokes, systemic embolism, transient ischemic attack , haemorrhage (bleeds), acute MI (heart attack) and death) and resulting functional disability. Dabigatran etexilate dosing approved in Canada was used: 150 mg bid for patients <80 years and 110 mg bid for patients' = 80 years.

This analysis uses the results from the RE-LY trial, the largest AF trial completed to date. In RE-LY, dabigatran etexilate 150 mg bid significantly reduced the risk of stroke and systemic embolism by 35 percent beyond the reduction achieved with well-controlled warfarin (median TTR 67%) in addition to reductions in life-threatening and intracranial bleeding. These groundbreaking results were shown in RE-LY, a PROBE (Prospective, Randomized, Open-label with Blinded Endpoint evaluation) trial designed to compare two fixed doses of the oral direct thrombin inhibitor dabigatran (110 mg and 150 mg bid) each administered in a blinded manner, with open label warfarin. Pradaxa 110 mg bid was shown to be as effective as warfarin.

AF is the most common heart rhythm condition, 12 affecting nearly one in four people over the age of 40 13 and 1% of the total population, rising to 10% in people over the age of 80. 12 People with AF are more likely to experience blood clots, which increases the risk of stroke by five-fold. Up to three million people worldwide suffer strokes related to AF each year which are typically severe and disabling, with one half of this population dying within one year. Strokes due to AF tend to be severe, with an increased likelihood of death (20%), and disability (60%). Many AF-related strokes can be prevented with appropriate antithrombotic therapy.

RE-LY (Randomized Evaluation of Long term anticoagulant therapY) was a global, phase III, randomised trial of 113 patients enrolled in over 900 centres in 44 countries. The PROBE (Prospective, Randomized, Open-label with Blinded Endpoint evaluation) trial was designed to compare two fixed doses of the oral direct thrombin inhibitor dabigatran (110mg and 150mg bid) each administered in a blinded manner, with open label warfarin (target INR of 2.0-3.0). Patients were followed-up in the study for a median of 2 years with a minimum of 1 year follow-up.

The primary endpoint of the trial was incidence of stroke (including haemorrhagic) or systemic embolism. Secondary outcome measures included all-cause death, incidence of stroke (including haemorrhagic), systemic embolism, pulmonary embolism, acute myocardial infarction, and vascular death (including death from bleeding).

Compared to well controlled warfarin, dabigatran etexilate showed in the trial: significant reduction in the risk of stroke and systemic embolism – including haemorrhagic strokes with dabigatran etexilate 150mg bid, significantly lower major bleeding events with dabigatran etexilate 110mg bid, comparable rates of stroke/systemic embolism with dabigatran etexilate 110mg bid, significantly lower life threatening and intracranial bleeding with both doses and significant reduction in vascular mortality with dabigatran etexilate 150mg bid.

Dabigatran etexilate is at the forefront of a new generation of oral anticoagulants/Direct Thrombin Inhibitors (DTIs) targeting a high unmet medical need in the prevention and treatment of acute and chronic thromboembolic diseases.

Potent antithrombotic effects are achieved with direct thrombin inhibitors by specifically blocking the activity of thrombin (both free and clot-bound), the central enzyme in the process responsible for clot (thrombus) formation. In contrast to vitamin-K antagonists, which variably act via different coagulation factors, dabigatran etexilate provides effective, predictable and consistent anticoagulation with a low potential for drug-drug interactions and no drug-food interactions, without the need for routine coagulation monitoring or dose adjustment.

Dabigatran etexilate has already been approved in 75 countries under the trademark Pradaxa (in Canada: Pradax) for the primary prevention of venous thromboembolic events (blood clots) in adults who have undergone elective total hip or elective total knee replacement surgery.

Boehringer Ingelheim’s clinical trial program to evaluate the efficacy and safety of dabigatran etexilate encompasses studies in: primary prevention of Venous Thrombo Embolism (VTE) in patients undergoing elective total hip and knee replacement surgeries, treatment of acute VTE, secondary prevention of VTE, stroke prevention in AF.