Individual variability in response to renin angiotensin aldosterone system inhibition predicts cardiovascular outcome in patients with type 2 diabetes: A primary care cohort study

Abstract

Aims: To assess variability in systolic blood pressure (SBP) and albuminuria (urinary albumin creatinine ratio [UACR]) responses in patients with type 2 diabetes mellitus initiating renin angiotensin aldosterone system (RAAS) inhibition, and to assess the association of response variability with cardiovascular outcomes. Material and Methods: We performed an observational cohort study in patients with type 2 diabetes who started RAAS inhibition between 2007 and 2013 (n = 1600). Patients were identified from general practices in the Netherlands. Individual response in SBP and UACR was assessed during 15 months’ follow-up. Patients were categorized as: good responders (∆SBP <0 mm Hg and ∆UACR <0%); intermediate responders (∆SBP <0 mm Hg and ∆UACR >0% or ∆SBP >0 mm Hg and ∆UACR <0%); or poor responders (∆SBP >0 mm Hg and ∆UACR >0%). Multivariable Cox regression was performed to test the association between initial RAAS inhibition response and subsequent cardiovascular outcomes. Results: After starting RAAS inhibition, the mean SBP change was −13.2 mm Hg and the median UACR was −36.6%, with large between-individual variability, both in SBP [5th to 95th percentile: 48.5-20] and UACR [5th to 95th percentile: −87.6 to 171.4]. In all, 812 patients (51%) were good responders, 353 (22%) had a good SBP but poor UACR response, 268 (17%) had a good UACR but poor SBP response, and 167 patients (10%) were poor responders. Good responders had a lower risk of cardiovascular events than poor responders (hazard ratio 0.51, 95% confidence interval 0.30-0.86; P =.012). Conclusions: SBP and UACR response after RAAS inhibition initiation varied between and within individual patients with type 2 diabetes treated in primary care. Poor responders had the highest risk of cardiovascular events, therefore, more efforts are needed to develop personalized treatment plans for these patients.