Dapagliflozin Improves Outcomes in Patients With Chronic Kidney Disease Regardless of Presence of Diabetes

Treatment with dapagliflozin (Farxiga) was found to lower the risk of hospitalization for any cause in patients with chronic kidney disease (CKD), either with or without type 2 diabetes (T2D), according to a study published in the Annals of Internal Medicine.

Dapagliflozin is indicated as an adjunct to diet and exercise to improve glycemic control in adults with T2D mellitus; to reduce the risk of hospitalization for heart failure (HF) in adults with T2D mellitus and either established cardiovascular disease (CVD) or multiple CVD risk factors; to reduce the risk of CVD death and hospitalization for HF in adults with HF with reduced ejection fraction; to reduce the risk of sustained estimated glomerular filtration rate (eGFR) decline, end-state kidney disease, cardiovascular death, and hospitalization for HF in adults with CKD at risk of progression.

Acute hospitalizations are more common in patients with CKD, according to the study authors. The use of sodium-glucose cotransporter-2 (SGLT2) inhibitors have been found to lower the risk of adverse cardiovascular outcomes and stop CKD from progressing in patients with T2D. For the current study, the authors conducted a post hoc analysis of the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial to evaluate the efficacy of dapagliflozin on first hospitalizations and all hospitalizations in patients with CKD with or without T2D.

The double-blind, multicenter, randomized, placebo-controlled DAPA-CKD trial analyzed the impact of dapagliflozin on kidney and cardiovascular outcomes. Enrollment criteria included being 18 years of age or older, a baseline eGFR of 25 to 75 mL/min/1.73 m2, and a urinary albumin-creatinine ratio (UACR) of 200 to 5000 mg/g.

Exclusion criteria included having type 1 diabetes, polycystic kidney disease, lupus nephritis, or antineutrophil cytoplasmic antibody–associated vasculitis, and receiving immunotherapy for other primary or secondary kidney diseases within the past 6 months. Participants were administered a stable dose of an angiotensin-converting enzyme inhibitor or an angiotensin-receptor blocker at least 4 weeks before randomization.

The trial randomized 4304 patients to receive 10 mg of dapagliflozin once daily or a placebo. Treatment was continued until diabetic ketoacidosis, pregnancy, or trial completion and hospitalization was included if patients started between the randomization date and censoring date of April 3, 2020.

Over a median of 2.4 years, there were 2072 hospitalizations, of which 1224 (59.1%) were prolonged or ended in death. Among all patients enrolled, 1224 (28.4%) patients had at least 1 hospitalization in the follow-up period, 808 patients (18.3%) had at least 1 hospitalization that was prolonged or ended in death, and 453 (10.5%) patients had 2 or more hospitalizations. The median duration of hospitalization was 7 days.

There were 566 patients (26.3%) found to have at least 1 hospitalization in the dapagliflozin cohort for an overall HR of 0.84 (95% CI, 0.75-0.94) compared with 658 (30.6%) patients in the placebo cohort. Dapagliflozin was found to lower the risk for prolonged hospitalization or death (HR, 0.83; 95% CI, 0.72-0.95), the composite of first hospitalization or death (HR, 0.83; 95% CI, 0.75-0.93), and all hospitalizations or death (rate ratio [RR], 0.79; 95% CI, 0.70-0.89).

Notably, dapagliflozin was more effective at preventing hospitalizations among patients 65 years of age or younger compared with patients 65 years of age or older. The results showed a mean increase of 3.3 days alive and out of the hospital per person-year in the dapagliflozin cohort compared with the placebo cohort.

Among all patients enrolled, 8.8% had at least 1 hospitalization related to infections and infestations, 7.5% for cardiac disorders, and 5.8% for renal and urinary disorders. Dapagliflozin lowered the rate of admissions for cardiac disorders (RR, 0.67; 95% CI, 0.53-0.86), renal and urinary disorders (RR, 0.61; 95% CI, 0.46-0.79), metabolism and nutrition disorders (RR, 0.61; 95% CI, 0.41-0.91), and neoplasms (RR, 0.62; 95% CI, 0.39-0.96).

Study limitations included hospitalizations being reported by site investigators and not centrally adjudicated; partial unmasking of the participants possibly occurring by investigators recording signs or symptoms, which may have biased reporting of all-cause or cause-specific hospitalizations; and that length of hospital stay may have been affected by factors other than disease severity, according to the authors.

The study authors concluded that dapagliflozin is effective in lowering the risk of hospitalization for patients with CKD with or without a diagnosis of T2D and increased the number of days alive and out of the hospital.

Reference

Schechter M, Jongs N, Chertow GM, et al. Effects of dapagliflozin on hospitalizations in patients with chronic kidney disease: a post hoc analysis of DAPA-CKD. Ann Intern Med. Published December 6, 2022. doi:10.7326/m22-2115.