Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The DAPA-HF trial demonstrated that dapagliflozin significantly reduces the risk of cardiovascular death and hospitalizations for heart failure compared to placebo, with a 26% reduction in composite cardiovascular events (hazard ratio 0.74, p<0.001). This indicates a clear clinical advantage over standard care, although the evidence does not include a direct comparison with sacubitril valsartan.
Cost effectiveness
The incremental cost-effectiveness ratio (ICER) for dapagliflozin is reported at £6,939 per QALY gained, which is well within NICE’s acceptable thresholds. The committee concluded that dapagliflozin is cost-effective as an add-on to optimized standard care.
Quality of life
The use of the Kansas City Cardiomyopathy Questionnaire (KCCQ) in the DAPA-HF trial showed improvements in patient-reported outcomes, indicating moderate gains in quality of life. However, the evidence is primarily based on secondary endpoints and may not fully capture long-term benefits.
Supporting Domains
Safety and Adverse Effects
The safety profile of dapagliflozin is generally acceptable, with most adverse events being similar to placebo. However, there are specific risks such as diabetic ketoacidosis that require monitoring, indicating some concerns but manageable risks.
Comparator Selection
Dapagliflozin was compared to standard care, which includes ACE inhibitors, ARBs, and sacubitril valsartan. While there are no direct comparisons with sacubitril valsartan, the indirect comparisons used are considered appropriate and relevant.
Patient Population and Subgroups
The DAPA-HF trial included a diverse population with chronic heart failure and reduced ejection fraction, and the findings are considered generalizable to Healthcare practice. However, some differences in demographics compared to the Healthcare population were noted.
Care Pathway Integration
Dapagliflozin can be integrated into existing treatment pathways with minor adjustments, as it is recommended to be used as an add-on to optimized standard care. This indicates a good fit within current clinical practices.
Resource Use and Cost Implications
The budget impact of dapagliflozin is manageable, with the potential for cost savings when added to standard care. The committee noted that the overall resource use is justifiable given the clinical benefits.
Evidence Quality and Robustness
The evidence from the DAPA-HF trial is robust, being a well-designed RCT with low bias. However, the lack of direct comparisons with all relevant alternatives introduces some uncertainty.
Uncertainty, Sensitivity, and Broader Impacts
While there are uncertainties regarding the indirect comparisons and the generalizability of the trial population, the overall context supports the use of dapagliflozin, particularly given the unmet need in chronic heart failure.
