Dapagliflozin and cardiovascular risks with worsening renal function
The coexistence of heart failure (HF) and chronic kidney disease (CKD) is associated with higher risks of clinical events than that conferred by either condition alone. While therapy in this high-risk group should be optimised, treatment is often interrupted or discontinued when renal function declines.
SGLT2 inhibitors are now a pivotal therapy for HF across the spectrum of left-ventricular ejection fraction. They can be initiated even in those with comorbid CKD, although deterioration in kidney function may be seen over time. Previous trials have demonstrated the efficacy and safety of dapagliflozin down to an eGFR of 30 mL/min/1.73 m², but there are limited data for continuing SGLT2 inhibitors in HF when eGFR falls below the thresholds for drug initiation.
The present study aimed to address this evidence gap by pooling data from the DAPA-HF and DELIVER trials to assess the impact of continuing treatment with dapagliflozin in HF when eGFR deteriorates below eGFR 25 mL/min/1.73 m².
Of 11,007 adults with HF randomised to receive dapagliflozin or placebo, 347 (3.2%) experienced a deterioration in kidney function to <25 mL/min/1.73 m² at least once during follow-up. The median time to deterioration was 121 days, and was similar in both treatment groups.
Amongst these participants, the risk of the primary composite outcome (time to first worsening HF event or cardiovascular death) was significantly higher (HR, 1.87) than in those who did not experience a decline in kidney function. However, the risk was lower with dapagliflozin compared with placebo both amongst those who did (HR, 0.53) and did not (HR, 0.78) experience deterioration in kidney function below eGFR 25 mL/min/1.73 m².
A higher risk of all safety outcomes (including study drug discontinuation or interruption) was found in those who experienced a deterioration in eGFR to <25 mL/min/1.73 m². However, rates between the treatment groups were similar.
Despite the heightened risk for the development of adverse cardiovascular outcomes in people with HF experiencing a deterioration in eGFR to <25 mL/min/1.73 m², these results suggest that the benefits of continuing dapagliflozin are greater than the risks.
The authors emphasise that these findings might only inform the continuation of SGLT2 inhibitor therapy and not their initiation in people with advanced CKD.
The full article can be read here.
