Intermittent non-adherence with ACE inhibitor treatment and its implications for clinical trials results.

For an individual congestive heart failure (CHF) patient to gain maximum benefit from their angiotensin converting enzyme (ACE) inhibitor treatment, it is important for him or her to adhere fully with treatment. Many studies suggest that non-adherence with drug treatment is common in CHF patients and that this leads to increased hospitalisation and even death. Since ACE inhibitors reduce mortality, it is self evident that non-adherence will increase mortality. As CHF patients tend to be elderly and on multiple treatments, it is unsurprising that non-adherence should be a common problem in this patient group. However, assessing treatment adherence is notoriously diYcult and all assessments of adherence are less than perfect. In the case of adherence with an ACE inhibitor, a unique opportunity presents itself—that is, to use serum ACE measurements to assess adherence. This measurement is very robust by a variety of technologies and intrasubject variability or assay related variability is minimal (> 2%), even in the unsuppressed state. We have previously established that this is a viable option by showing that a serum ACE concentration of > 20 u/l was 86% sensitive and 95% specific in its ability to identify non-adherence with an ACE inhibitor. Importantly, the dose of ACE inhibitor has virtually no impact on the ability of serum ACE to indicate ACE inhibitor non-adherence because serum ACE hits its nadir even with a tiny dose of an ACE inhibitor. In a cross sectional study of routine patients, we recently found that 18% of CHF patients exhibited < 70% adherence with their ACE inhibitor treatment. How variable adherence with ACE inhibitor treatment is over time within the same CHF individuals has not previously been assessed. This is particularly relevant to the interpretation of the results for patients taking part in long term clinical mortality trials since nonadherence with treatment could easily lead to a false negative result or more likely an under appreciation of treatment eVect at a variety of levels, whether symptoms, morbidity (hospitalisation rates) or mortality.