Nonadherence with angiotensin-converting enzyme inhibitor therapy: a comparison of different ways of measuring it in patients with chronic heart failure

J Am Coll Cardiol. 1999 Dec;34(7):2072-7. doi: 10.1016/s0735-1097(99)00439-8.


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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angiotensin I / blood
  • Angiotensin II / blood
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Biomarkers / blood
  • Biomarkers / urine
  • Chronic Disease
  • Diuretics / therapeutic use
  • Drug Therapy, Combination
  • Echocardiography
  • Furosemide / therapeutic use
  • Heart Failure / diagnosis
  • Heart Failure / drug therapy*
  • Heart Failure / metabolism
  • Humans
  • Lisinopril / therapeutic use*
  • Oligopeptides / blood
  • Oligopeptides / urine
  • Peptidyl-Dipeptidase A / blood
  • Radionuclide Ventriculography
  • Treatment Outcome
  • Treatment Refusal* / statistics & numerical data


  • Angiotensin-Converting Enzyme Inhibitors
  • Biomarkers
  • Diuretics
  • Oligopeptides
  • Angiotensin II
  • Furosemide
  • Angiotensin I
  • Lisinopril
  • Peptidyl-Dipeptidase A
  • goralatide