The Effects of Antitussive Treatment of ACE Inhibitor-Induced Cough on Therapy Compliance: A Prescription Sequence Symmetry Analysis

Abstract

A common adverse effect of angiotensin-converting enzyme inhibitors (ACEI) is a persistent dry cough. Physicians and pharmacists who fail to recognise dry cough to be ACEI related may prescribe antitussives, instead of recommended ACEI substitution. The aim of this study was to determine the influence of antitussive treatment of ACEI-induced cough on ACEI therapy compliance. Prescription data from community pharmacies between 2000 and 2012 were retrieved from the IADB.nl database (InterAction Database) in The Netherlands. A prescription sequence symmetry analysis was used to determine whether antitussive agents were prescribed more often following ACEI initiation (cases) than the other way around (controls). ACEI therapy compliance was assessed using the proportion of days covered (PDC) method; patients with a PDC of at least 80 % were considered compliant. Compliance was compared between patients receiving antitussives for ACEI-induced cough and patients receiving antitussives for other reasons and patients who did not receive antitussives. A total of 1,898 starters of ACEI and antitussives within a half-year time span were included. A significant excess of patients received antitussives after ACEI initiation compared with before ACEI initiation (1,269 cases vs. 629 controls), yielding a sequence ratio of 2.0 (95 % CI 1.8-2.2). The estimated proportion of patients with ACEI-induced cough receiving antitussives decreased over time: from 20.4 % in 2000-2004 to 8.0 % in 2008-2012. ACEI therapy compliance in patients receiving antitussives due to ACEI initiation was 52.4 %, significantly lower than compliance in control patients receiving antitussives for cough unrelated to ACEI (75.5 %, P < 0.001) and control patients who did not receive antitussives (75.2 %, P < 0.001). Many patients receive antitussives after ACEI initiation. This suggests that ACEI-induced cough is often either not recognized as being ACEI related or is symptomatically treated. Such prescription behaviour may decrease ACEI therapy compliance.