Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The evidence suggests that bempedoic acid with ezetimibe may help lower LDL-C levels when other lipid-lowering therapies have not been effective. However, there is no direct comparison with alirocumab or evolocumab, and an indirect comparison indicates that bempedoic acid with ezetimibe may not be as effective at reducing LDL-C levels as these alternatives. This leads to a rating of B++ as the efficacy is comparable but lacks a clear edge.
Cost effectiveness
The cost-effectiveness estimates for bempedoic acid with ezetimibe are within what NICE considers acceptable for Healthcare resources, particularly for the population where statins are contraindicated or not tolerated. The ICER for this population is less than £20,000 per QALY gained, indicating strong economic value.
Quality of life
The document does not provide specific data on HRQoL improvements associated with bempedoic acid with ezetimibe. While it is noted that the treatment is an oral preparation and may be easier for patients to use compared to injectable alternatives, there is no substantial evidence of significant quality-of-life gains, leading to a rating of B+.
Supporting Domains
Safety and Adverse Effects
The safety profile of bempedoic acid with ezetimibe appears acceptable, with no significant adverse events reported that would undermine its benefits. The document indicates that the treatment is suitable for patients who cannot tolerate statins, suggesting a good tolerability profile.
Comparator Selection
The trials included in the evidence base did not directly compare bempedoic acid with ezetimibe against the most relevant comparators (alirocumab and evolocumab). While there are indirect comparisons, the lack of direct evidence limits the robustness of the findings, resulting in a B++ rating.
Patient Population and Subgroups
The patient population in the trials included individuals who may not reflect the typical clinical practice, particularly regarding prior treatment with ezetimibe. The committee noted limitations in subgroup analyses, which affects the generalizability of the results.
Care Pathway Integration
Bempedoic acid with ezetimibe is positioned well within the existing treatment pathway for patients who cannot tolerate statins. The committee noted that it is an oral preparation, which facilitates integration into current clinical practice with minimal disruption.
Resource Use and Cost Implications
The economic analysis indicates that bempedoic acid with ezetimibe represents a cost-effective use of Healthcare resources, particularly with the commercial arrangement providing a discount. This suggests manageable budget impacts aligned with planning.
Evidence Quality and Robustness
While the evidence base includes several trials, there are concerns regarding the methodological quality and the applicability of the results to the intended patient population. The lack of direct comparisons and the reliance on indirect evidence contribute to a B+ rating.
Uncertainty, Sensitivity, and Broader Impacts
There are significant uncertainties regarding the long-term effects of bempedoic acid on cardiovascular outcomes and the appropriateness of the ICER estimates. The committee expressed concerns about the robustness of the evidence, leading to a B+ rating.
