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.


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.
Azizi
Michel
M
Centre d'Investigations Cliniques, Hôpital Européen Georges Pompidou, 20-40 rue Leblanc, 75908 Paris cedex 15, France. michel.azizi@egp.aphp.fr
Ménard
Joël
J
Peyrard
Séverine
S
Lièvre
Michel
M
Marre
Michel
M
Chatellier
Gilles
G
D000368:Aged; D000419:Albuminuria / Q000523:psychology / Q000652:urine; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D015415:Biomarkers / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000523:psychology* / Q000652:urine; D003925:Diabetic Angiopathies / Q000188:drug therapy / Q000523:psychology* / Q000652:urine; D004311:Double-Blind Method; D005260:Female; D019983:Guideline Adherence; D006801:Humans; D006973:Hypertension / Q000523:psychology / Q000652:urine; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000652:urine*; D010349:Patient Compliance; D010820:Physicians; D010919:Placebos; D011507:Proteinuria / Q000523:psychology / Q000652:urine
D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D009842:Oligopeptides; D010919:Placebos; C058504:goralatide