Canagliflozin as Primary Prevention: Findings from CREDENCE

The sodium-glucose co-transporter 2 (SGLT2) inhibitor canagliflozin reduces cardiovascular and renal events in diabetic patients with chronic kidney disease—even those with no previous history of cardiovascular disease, according to a clinical trial report in Circulation.

The analysis included 4401 individuals from the phase 3 CREDENCE trial (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) with type 2 diabetes and CKD but no previous cardiovascular disease. In CREDENCE, patients were randomly assigned to canagliflozin or placebo, while continuing optimized standard therapy.

Compared to 2220 secondary prevention patients, those in the primary prevention group were younger, 61 versus 65 years; more likely to be women, 37% versus 31%; and had a shorter duration of diabetes, 15 versus 16 years. Estimated glomerular filtration rate and urine albumin-to-creatinine ratio were similar between groups.

On analysis of the primary outcome, canagliflozin was associated with a lower risk of cardiovascular events overall, hazard ratio (HR) 0.80; in the primary prevention group, HR 0.68; and in the secondary prevention group, HR 0.85. All of the component outcomes were also lower with canagliflozin: HR 0.78 for cardiovascular death, 0.81 for nonfatal myocardial infarction, and 0.80 for nonfatal stroke.

Rates of the primary composite renal outcome (end stage kidney disease, doubling of serum creatinine, or renal or cardiovascular death) were also lower with canagliflozin: HR 0.70 overall, 0.69 in the primary prevention group, and 0.70 in the secondary prevention group. Heart failure hospitalization was significantly reduced, with no increase in fractures or amputations. Numbers needed to treat for the primary composite renal outcome were 19 in the primary prevention group and 26 in the secondary prevention group.

It has been uncertain whether the benefits of SGLT2 inhibition in patients with type 2 diabetes and CKD extend to those without a history of previous cardiovascular disease. This analysis of CREDENCE data shows “robust and consistent” reductions in major cardiovascular and renal outcomes in this group of primary prevention patients.

The investigators conclude: “These data support the initiation of canagliflozin in a much broader patient population with type 2 diabetes including those with glycated hemoglobin as low as 6.5% and in patients with estimated glomerular filtration rate between 30 to 45 mL/min/1.73 m2 with expected reductions in renal and cardiovascular outcomes” [Mahaffey KW, et al. Canagliflozin and cardiovascular and renal outcomes in type 2 diabetes and chronic kidney disease in primary and secondary cardiovascular prevention groups: results from the randomized CREDENCE trial. Circulation 2019; DOI: 10.1161/CIRCULATIONAHA.119.042007].

September 2019 (Vol. 11, Number 9)