Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
Empagliflozin demonstrated a clear clinical advantage in reducing the risk of cardiovascular death and hospitalizations for heart failure compared to placebo, with a 25% reduction in the primary outcome in the EMPEROR-Reduced trial. However, the lack of direct comparison with dapagliflozin limits the strength of the evidence.
Cost effectiveness
The cost-effectiveness estimates for empagliflozin are within NICE’s acceptable thresholds, and the probabilistic analysis suggests it is likely to be cost-effective compared to dapagliflozin, supporting its recommendation.
Quality of life
The use of the Kansas City Cardiomyopathy Questionnaire (KCCQ) in the economic model indicates moderate improvements in quality of life, although the evidence is primarily based on indirect comparisons and may not fully capture the long-term benefits.
Supporting Domains
Safety and Adverse Effects
Empagliflozin has a good safety profile with manageable adverse effects, similar to those of other SGLT2 inhibitors, and no significant safety concerns were raised in the trials.
Comparator Selection
The appraisal committee identified dapagliflozin as the most appropriate comparator, and while there were no direct comparisons, the indirect treatment comparison suggests similar efficacy between empagliflozin and dapagliflozin.
Patient Population and Subgroups
The EMPEROR-Reduced trial included a diverse population, although there are concerns regarding the representativeness of the trial population compared to the Healthcare population, particularly regarding age and comorbidities.
Care Pathway Integration
Empagliflozin can be integrated into existing treatment pathways as an add-on to optimized standard care, requiring only minor adjustments in clinical practice.
Resource Use and Cost Implications
The budget impact of empagliflozin is manageable, and the treatment is expected to be resource-efficient, aligning with Healthcare planning.
Evidence Quality and Robustness
The evidence base is supported by a robust Phase III trial (EMPEROR-Reduced) and indirect comparisons, although the reliance on indirect evidence introduces some uncertainty.
Uncertainty, Sensitivity, and Broader Impacts
While there are uncertainties related to the indirect comparisons and the generalizability of trial results, the context of unmet need and potential benefits supports a favorable assessment.
