Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
Dabigatran 150 mg twice daily demonstrated a statistically significant reduction in the incidence of stroke or systemic embolism compared to warfarin (HR 0.65, 95% CI 0.52 to 0.81). The RE-LY trial, which is a robust Phase 3 study, supports this evidence, showing clear clinical advantages in key outcomes, although the 110 mg dose did not show significant differences.
Cost effectiveness
The ICER for dabigatran compared to warfarin was reported as £6,264 per QALY gained for the 150 mg dose, which is well within the acceptable cost-effectiveness threshold. The analysis was robust across various scenarios, indicating a strong economic value.
Quality of life
The HRQoL data from the RE-LY trial’s sub-study indicated that the population was reasonably representative, and while specific utility values were not reported, the overall findings suggest moderate improvements in quality of life for patients treated with dabigatran compared to warfarin.
Supporting Domains
Safety and Adverse Effects
Dabigatran showed a lower incidence of haemorrhagic stroke and life-threatening bleeds compared to warfarin, although it was associated with higher rates of gastrointestinal bleeding. Overall, the safety profile is acceptable with manageable adverse events.
Comparator Selection
The RE-LY trial directly compared dabigatran with warfarin, which is the current standard of care for atrial fibrillation. This direct comparison strengthens the evidence base and relevance of the findings.
Patient Population and Subgroups
The trial population included a broad range of patients with atrial fibrillation and relevant risk factors, making the results generalizable to the UK population. Subgroup analyses were also conducted, although some were post hoc.
Care Pathway Integration
Dabigatran can be integrated into existing care pathways without significant changes, as it does not require INR monitoring, which is a major advantage over warfarin. Minor adjustments may be needed for patient education.
Resource Use and Cost Implications
The cost implications of dabigatran are manageable, with a daily cost of £2.52, which is significantly lower than the costs associated with warfarin monitoring. The overall resource use is favorable.
Evidence Quality and Robustness
The evidence is primarily based on the well-conducted RE-LY trial, which is a large Phase 3 RCT with low bias risk. The robustness of the evidence is further supported by additional analyses and systematic reviews.
Uncertainty, Sensitivity, and Broader Impacts
While there are some uncertainties regarding the generalizability of the trial results to the broader UK population, the overall context supports the use of dabigatran, especially given the unmet need in atrial fibrillation management.
