For patients with CKD who both are or are not undergoing hemodialysis, daprodustat is non-inferior to the injectable erythropoiesis-stimulating agent (ESA) for anemia, according to two studies published in the New England Journal of Medicine. Researchers conducted a phase III trial of 2,964 patients with CKD undergoing dialysis with a hemoglobin level of 8.0-11.5 g/dL who were randomly assigned to either daprodustat or ESA. From baseline to weeks 28-52, the mean changes in hemoglobin levels were 0.28±0.02 g/dL and 0.10±0.02 g/dL in the daprodustat and ESA groups, respectively (difference, 0.18 g/dL). A major adverse cardiovascular event occurred in 25.2% and 26.7% of patients in the daprodustat and ESA groups, respectively, during a median follow-up of 2.5 years (HR, 0.93; 95% CI, 0.81-1.07), meeting the prespecified noninferiority margin. In a second study, investigators compared daprodustat with darbepoetin alfa for anemia in 3,872 patients with CKD who were not undergoing dialysis. From baseline to weeks 28-52, the mean changes in hemoglobin levels were 0.74±0.02 and 0.66±0.02 g/dL in the daprodustat and darbepoetin alfa groups, respectively (difference, 0.08 g/dL).
Chlorthalidone Aids BP Control in Patients With CKD & HTN
Compared with placebo, chlorthalidone therapy improves blood pressure control at 12 weeks in patients with advanced CKD and poorly controlled hypertension, according to a study published in the New England Journal of Medicine. Rajiv Agarwal, MD, and colleagues randomized 160 patients with stage 4 CKD and poorly controlled hypertension 1:1 to chlorthalidone at an initial dose of 12.5 mg/ day, with increases every 4 weeks up to a maximum of 50 mg/day, or placebo. Overall, 76% of patients had diabetes and 60% were receiving loop diuretics. At baseline, patients have been prescribed a mean of 3.4±1.4 antihypertensive medications. From baseline to 12 weeks, the adjusted changes in 24-hour systolic blood pressures were −11.0 mmHg and −0.5 mmHg in the chlorthalidone and placebo groups, respectively. From baseline to 12 weeks, the percent change in the urinary albumin-to-creatinine ratio was 50 percentage points lower with chlorthalidone than with placebo. The chlorthalidone group more often had hypokalemia, reversible increases in serum creatinine level, hyperglycemia, dizziness, and hyperuricemia.
