Dapagliflozin (Farxiga), reduced the worsening of renal function or risk of cardiovascular (CV) or renal death by 39% compared to placebo in patients with chronic kidney disease (CKD), at stages 2-4 and elevated urinary albumin excretion. announced AstraZeneca India based on phase 3 DAPA-CKD study. The sodium-glucose co-transporter 2 (SGLT2) drug alleviated the rate of progression of CKD in both type 2 diabetic as well as non-diabetic patients. The findings of the trial were recently presented at the European Society of Cardiology 2020 Congress.
According to the Global Burden of the Disease Study 2015, CKD is the 12th most common cause of death with a 37.1% rise in mortality over 10 years. It is a serious, progressive condition defined by decreased kidney function and/or kidney damage, affecting nearly 70 crore people worldwide, many of them still undiagnosed. The prevalence of CKD in India is estimated to be 17.2%. The most common causes of the disease are diabetes, hypertension and glomerulonephritis.
The DAPA-CKD trial included 4,304 patients 18 and older with CKD into a global study, with 201 patients from India. The participants had an estimated glomerular filtration rate (eGFR) ≥25 and ≤75 mL/min/1.73m2 and urinary albumin to creatinine ratio between ≥200 mg/g and ≤5000 mg/g. They were stabilised on a maximum tolerated dose of an angiotensin-converting-enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB), unless contraindicated, for at least 4 weeks.
During a median follow-up of 2.4 years, there were 197 primary end point events with dapagliflozin and 312 with placebo. Hazard ratio for the primary end point was 0.61 (95% CI, 0.51-0.72; P = .00000028). The benefit was consistent for patients with and without diabetes.
Dapagliflozin achieved all 3 secondary end points, including a 31% risk reduction in all-cause mortality (HR, 0.69; 95% CI, 0.53-0.88; P = .0035). Other secondary end points were a 29% risk reduction in hospitalisation for heart failure or cardiovascular death (HR, 0.71; 95% CI, 0.55-0.92; P = .0089) and a 44% risk reduction in worsening renal function or death from kidney failure (HR, 0.56; 95% CI, 0.45-0.68; P < .0001). Slightly more patients had serious adverse events in the placebo group than in the dapagliflozin group (33.9% vs 29.5%) and the number that discontinued the drug was the same (5.7% vs 5.5%).
The DAPA-CKD study concluded globally on 30th March 2020 based on its effectiveness and safety. Dapagliflozin was recently approved by USFDA as well as in India to reduce the risk of CV death and hospitalisation for heart failure (hHF) in adults with heart failure (NYHA class II-IV) with reduced ejection fraction (HFrEF) with and without T2D.
Dapagliflozin is currently being assessed in patients with heart failure (HF) in the DELIVER (HF with preserved ejection fraction, HFpEF) and DETERMINE (HFrEF and HFpEF) trials, as well as in patients without T2D following an acute myocardial infarction (MI) or heart attack in the DAPA-MI trial – a first of its kind, indication-seeking registry-based randomised controlled trial.