Nonadherence with angiotensin-converting enzyme inhibitor therapy: a comparison of different ways of measuring it in patients with chronic heart failure.
OBJECTIVE
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.
Struthers
A D
AD
Department of Clinical Pharmacology and Therapeutics, Ninewells Hospital and Medical School, Dundee, UK.
MacFadyen
R
R
Fraser
C
C
Robson
J
J
Morton
J J
JJ
Junot
C
C
Ezan
E
E
D000368:Aged; D000803:Angiotensin I / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002908:Chronic Disease; D004232:Diuretics / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004452:Echocardiography; D005665:Furosemide / Q000627:therapeutic use; D006333:Heart Failure / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D017706:Lisinopril / Q000627:therapeutic use*; D009842:Oligopeptides / Q000097:blood / Q000652:urine; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D015635:Radionuclide Ventriculography; D016896:Treatment Outcome; D016312:Treatment Refusal / Q000706:statistics & numerical data
D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D004232:Diuretics; D009842:Oligopeptides; D000804:Angiotensin II; D005665:Furosemide; D000803:Angiotensin I; D017706:Lisinopril; D007703:Peptidyl-Dipeptidase A; C058504:goralatide