Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
Dapagliflozin shows moderate benefit over current care, significantly reducing the combined risk of cardiovascular death or first heart failure event compared to placebo plus standard care. However, the evidence for all-cause and cardiovascular mortality is uncertain, as the confidence intervals cross 1, indicating that the results are not statistically significant.
Cost effectiveness
The cost-effectiveness estimates for dapagliflozin are below NICE’s acceptable threshold for Healthcare resources, with the base-case ICER reported at £8,975 per QALY gained, indicating a clear cost-effective use of resources.
Quality of life
The evidence suggests that dapagliflozin could improve quality of life for patients with chronic heart failure with preserved or mildly reduced ejection fraction, as indicated by the patient experts who emphasized the importance of both quality of life and survival. However, the improvements are moderate and based on indirect evidence.
Supporting Domains
Safety and Adverse Effects
Dapagliflozin has a very good safety profile, with adverse events primarily being mild or moderate. The committee concluded that there is unlikely to be an increased risk of amputation, which further supports its favorable safety profile.
Comparator Selection
The evaluation appropriately compared dapagliflozin against standard care, which includes loop diuretics and symptomatic treatments for comorbidities. The committee agreed that the choice of comparators was appropriate and relevant.
Patient Population and Subgroups
The trial population is broadly representative of the intended patient population, although it did not include participants from the UK. The committee noted that the North American population is likely generalizable to UK clinical practice.
Care Pathway Integration
Dapagliflozin can be integrated into existing care pathways with minor adjustments, as it is already prescribed for heart failure with reduced ejection fraction. The committee noted that GPs are experienced in prescribing dapagliflozin.
Resource Use and Cost Implications
The budget impact of dapagliflozin is manageable, with the annual treatment cost estimated at £477.30. The committee concluded that the resource implications are aligned with planning and do not raise significant concerns.
Evidence Quality and Robustness
The evidence is based on a robust Phase 3 RCT (DELIVER), although there are some methodological concerns regarding the generalizability of the trial population and the modeling approach used for cost-effectiveness.
Uncertainty, Sensitivity, and Broader Impacts
While there is some uncertainty regarding the treatment effect on mortality and the appropriateness of the modeling approach, the committee concluded that the overall context supports the use of dapagliflozin, especially given the unmet need in this patient population.
