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

  1. Michel Azizi, MD, PHD123,
  2. Joël Ménard, MD123,
  3. Séverine Peyrard, MSC123,
  4. Michel Lièvre, MD, PHD4,
  5. Michel Marre, MD, PHD5 and
  6. Gilles Chatellier, MD, MSC236
  1. 1Institut National de la Santé et de la Recherche Médicale, CIC 9201, Paris, France
  2. 2Assistance Publique Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France
  3. 3Faculté de Médecine, Université Paris Descartes, Paris, France
  4. 4Faculté de Médecine Laënnec, EA3736, Hôpitaux de Lyon, Lyon, France
  5. 5Institut National de la Santé et de la Recherche Médicale, U695, and Assistance Publique Hôpitaux de Paris, Service d’Endocrinologie Diabétologie Nutrition, Groupe Hospitalier Bichat-Claude Bernard, Paris, France
  6. 6Institut National de la Santé et de la Recherche Médicale, CIE 4, Paris, France
  1. Address correspondence and reprint requests to Michel Azizi, MD, PhD, Centre d’Investigations Cliniques, Hôpital Européen Georges Pompidou, 20-40 rue Leblanc, 75908 Paris cedex 15, France. E-mail: michel.azizi{at}egp.aphp.fr

Abstract

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 ≥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 ≥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.

Footnotes

  • A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted March 6, 2006.
    • Received January 31, 2006.
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  1. doi: 10.2337/dc06-0255 Diabetes Care June 2006 vol. 29 no. 6 1331-1336
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