Sex-Differences in Initiation of Renin-Angiotensin System Inhibitors in Patients with Type 2 Diabetes and Albuminuria

Abstract

Background: Whether sex-differences exist with regard to rate of initiation of renin-angiotensin inhibitors (RASi) in patients with type 2 diabetes (T2D) and albuminuria is currently unknown, and potential sex-differences in the effect of RASi on mortality remains untested. \n \nMethods: Using Danish nationwide registers, we included T2D patients with de novo albumin-creatinine ratio >30 mg/g at age >50 years between 1 January 2014 and 20 March 2019. Patients with prior end-stage renal disease, acute kidney injury <90 days, and previous prescription of RASi <15 years were excluded. During an initial 30-day follow-up period, we used multiple Cox regression to study the hazard ratio (men vs women) of RASi initiation. In 30-day survivors, we used another multiple Cox regression to compare mortality between patients who initiated RASi and patients who did not yet initiate RASi. Reported were the sex-specific standardized one-year risk differences for fixed comorbidity distribution according to RASi treatment. \n \nFindings: In 16,145 patients (43% women), 960 (10.5%) men and 585 (8.5%) women initiated RASi treatment within 30 days after index. The adjusted rate of RASi initiation was higher in men compared to women (hazard ratio 1.22 [1.10;1.36]). A total of 45 patients (33% women) died within 30 days, and 5 patients (40% women) emigrated. In 30-day survivors, the standardized one-year mortality risk was 2.6% [2.0;3.2] in men who readily initiated RASi, and 4.0% [3.7;4.4] in men who did not (absolute reduction: -1.5% [-2.1;-0.8]). In contrast, no reduction was observed in women (0.2% [-0.7;1.1]). \n \nInterpretation: In patients with T2D and albuminuria, men were more likely to initiate RASi, and timely initiation of RASi was shown to be associated with greater benefit on one-year standardized risk of death compared to women. Sex-differences in the effect of RASi on all-cause death need testing in clinical trials. \n \nFunding: This work was funded by the Danish Heart Foundation (Grant number: 18-R121-A8218). \n \nDeclaration of Interests: None. \n \nEthics Approval Statement: Retrospective register studies do not need ethical approval in Denmark. The Danish Data Protection Agency has approved the project (approval number P-2019-393).