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CLINICAL STUDIES

Nonadherence with angiotensin-converting enzyme inhibitor therapy

A comparison of different ways of measuring it in patients with chronic heart failure

Allan D. Struthers, MD^*, Robert MacFadyen, MD^*, Callum Fraser, PhD, Jess Robson^*, James J. Morton, PhD, Christophe Junot, BSc and Eric Ezan, PhD

^* Department of Clinical Pharmacology and Therapeutics, Ninewells Hospital and Medical School, Dundee, DD1 9SY, UK
Directorate of Biochemical Medicine, Ninewells Hospital and Medical School, Dundee, DD1 9SY, UK
CEA Service de Pharmacologie et d’Immunologie, Gif-sur-Yvette, France
Department of Medicine and Therapeutics, Western Infirmary, Glasgow, G11 6NT, UK

Manuscript received March 2, 1999; revised manuscript received June 18, 1999, accepted August 23, 1999.

Reprint requests and correspondence: Professor A. D. Struthers, Department of Clinical Pharmacology and Therapeutics, Ninewells Hospital, Dundee DD1 9SY, UK

OBJECTIVES

This study was designed to compare different proposed methods of assessing adherence with angiotensin-converting enzyme (ACE) inhibitor (ACEI) therapy in chronic heart failure.

BACKGROUND

The use of ACEIs in chronic heart failure gives us a unique opportunity to assess a patient’s adherence by measuring whether the expected biochemical effect of an ACEI is present in the patient’s bloodstream. In fact, there are several different ways of assessing ACE in vivo: these are serum ACE activity itself, plasma N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP), urine AcSDKP, plasma angiotensin I (AI), plasma angiotensin II (AII), or the AII/AI ratio.

METHODS

Patients with chronic heart failure (n = 39) were randomized to regimens of ACEI nonadherence for one week, ACEI adherence for one week or two versions of partial adherence for one week, after which the above six tests were performed.

RESULTS

All six tests significantly distinguished between full nonadherence for one week and full or partial adherence. Only plasma AcSDKP produced a significantly different result between partial adherence and either full adherence or full nonadherence for one week. In terms of their ability to distinguish full nonadherence from full adherence, plasma AcSDKP was 89% sensitive and 100% specific with an area under its ROC of 0.95. Corresponding figures for urine AcSDKP were 92%, 97% and 0.95 and for serum ACE they were 86%, 95% and 0.90.

CONCLUSIONS

All six tests distinguished full nonadherence from all other forms of adherence. The rank order of performance was plasma AcSDKP, urine AcSDKP, serum ACE, AII/AI ratio and plasma AII followed by plasma AI.

Abbreviations and Acronyms   ACE = angiotensin-converting enzyme   ACEI = angiotensin-converting enzyme inhibitor   AI = Angiotensin I   AII = Angiotensin II   AcSDKP = N-acetyl-seryl-aspartyl-lysyl-proline   FAPGG = furylacrylolyphenylalanylglycylglycine

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