Cardiovascular outcomes in patients with type 2 diabetes and reduced eGFR and albuminuria: a REWIND post hoc subgroup analysis

Abstract

Background and aims: Diabetic kidney disease affects up to 40% of people with diabetes and is associated with higher cardiovascular (CV) risk. REWIND was a multicentre, randomised, double-blind, placebo-controlled trial with a primary outcome of first occurrence of the composite endpoint of CV death, nonfatal myocardial infarction, or nonfatal stroke (Major Adverse Cardiovascular Event [MACE]-3). Dulaglutide treatment reduced the incidence of MACE-3 in patients with type 2 diabetes (T2D) with or without established CV disease. This REWIND post hoc subgroup analysis evaluated the effect of dulaglutide on MACE-3 in patients with an eGFR<60 and ≥60 mL/min/1.73m2 and patients with micro-/macro-albuminuria (UACR ≥30 mg/g) or normoalbuminuria (UACR <30 mg/g). Materials and methods: Eligible patients were those ≥50 years old with T2D who had either a previous CV event or CV risk factors. Patients were randomised (1:1) to dulaglutide 1.5 mg or placebo, both in addition to standard of care. A Cox proportional hazards model with treatment, eGFR subgroup (<60 and ≥60 mL/min/1.73 m2), and treatment by eGFR subgroup interaction was used to analyze time to the first occurrence of MACE-3. These analyses were also conducted for albuminuria subgroups (micro-/macro-albuminuria or normoalbuminuria). Estimates of hazard ratios (HR) with 95% confidence intervals (CI) were calculated for each subgroup. Results: At baseline, 2,199 of 9,901 patients (22.2%) had an eGFR <60mL/min/1.73 m2, 2,676 (27.0%) had microalbuminuria, and 791 (8.0%) had macroalbuminuria. This post hoc subgroup analysis showed that the reduction in MACE-3 with dulaglutide treatment was of consistent magnitude and direction in patients with eGFR <60 and ≥60 mL/min/1.73 m2 (HR [95% CI]: 0.93 [0.76-1.13] and 0.86 [0.75-0.99], respectively; interaction p=0.545). Similarly, MACE-3 risk reduction was consistent in patients with micro-/macro-albuminuria or normoalbuminuria (HR [95% CI]: 0.84 [0.72-0.99] and 0.93 [0.79-1.10], respectively; interaction p=0.374). Conclusion: Regardless of baseline eGFR or albuminuria status, dulaglutide reduces MACE-3 outcomes in patients with T2D and established CV disease or multiple CV risk factors.