J Am Coll Cardiol. 2023 Aug 23:S0735-1097(23)06532-4. doi: 10.1016/j.jacc.2023.08.026. Online ahead of print.
BACKGROUND: SGLT-2 inhibitors are guideline-recommended in the management of heart failure(HF). While these therapies can be initiated even in patients with comorbid CKD, some patients may face deterioration in kidney function over time.
OBJECTIVES: To examine the safety and efficacy of continuing SGLT-2 inhibitors in HF when eGFR falls below thresholds for initiation.
METHODS: Associations between a deterioration in eGFR below 25 ml/min/1.73m2 , efficacy and safety outcomes, and treatment with dapagliflozin were evaluated in time-updated Cox proportional hazards models in a participant-level pooled analysis of DAPA-HF and DELIVER.
RESULTS: Among 11,007 patients, 347 (3.2%) experienced a deterioration in eGFR to <25ml/min/1.73m2 at least once in follow-up. These patients had a higher risk of the primary composite outcome (HR 1.87; 95% CI: 1.48-2.35, p<0.001). The risk of the primary outcome was lower with dapagliflozin compared with placebo both among patients who did (HR 0.53; 95% CI: 0.33-0.83) and did not (HR 0.78; 95% CI: 0.72-0.86) experience deterioration in kidney function below eGFR<25ml/min/1.73m2 (Pinteraction=0.17). The risk of safety outcomes including drug discontinuation were higher among patients with deterioration in eGFR<25ml/min/1.73m2 ; however, rates remained similar between treatment groups including among those who remained on study drug.
CONCLUSIONS: Patients with deterioration of kidney function below eGFR 25ml/min/1.73m2 had elevated risks of CV outcomes yet appeared to benefit from continuation of dapagliflozin with no excess in safety outcomes between treatment groups. The benefit-to-risk ratio may favor continuation of dapagliflozin treatment in patients with HF experiencing deterioration of kidney function.