Assessment of patients' and physicians' compliance to an ACE inhibitor treatment based on urinary N-acetyl Ser-Asp-Lys-Pro determination in the Noninsulin-Dependent Diabetes, Hypertension, Microalbuminuria, Proteinuria, Cardiovascular Events, and Ramipril (DIABHYCAR) study.

OBJECTIVE

The purpose of this study was to assess patients' and physicians' compliance with ACE inhibitor treatment, by measuring an endogenous biomarker of ACE inhibition, urinary N-acetyl-Ser-Asp-Lys-Pro (AcSDKP), in the Noninsulin-Dependent Diabetes, Hypertension, Microalbuminuria, Proteinuria, Cardiovascular Events, and Ramipril (DIABHYCAR) trial, which compared ramipril (1.25 mg o.d.) with placebo in 4,912 patients with type 2 diabetes and microalbuminuria/proteinuria.

RESEARCH DESIGN AND METHODS

The urine AcSDKP-to-creatinine ratio was measured blind to treatment in all participants who completed follow-up and provided spot urine samples (n = 1,871).

RESULTS

The median urinary AcSDKP-to-creatinine ratio was six times higher for ramipril than for placebo. Urinary AcSDKP-to-creatinine ratios displayed a bimodal distribution in both groups, with a very large intergroup overlap. Based on cluster analysis, we defined truly adherent ramipril patients as those with a ratio > or =4 nmol/mmol and truly adherent placebo patients as those with a ratio < 4 nmol/mmol. After excluding patients withdrawing prematurely from the study or known to have used a nonstudy ACE inhibitor, 27.3% of the 597 ramipril patients had ratios <4, indicating poor compliance, and 9.7% of the 621 placebo patients had ratios > or =4, indicating intake of a nonstudy ACE inhibitor. Correcting for compliance by using AcSDKP-guided analysis affected surrogate outcome results (decrease in systolic blood pressure and urinary albumin excretion) only slightly.

CONCLUSIONS

The systematic use of spot urinary AcSDKP determination facilitated the detection of defects in compliance with ACE inhibitor treatment in both patients and physicians. Urinary AcSDKP measurement could be a useful biomarker for assessing compliance with ACE inhibition in the routine care of diabetic patients.