ACEi-induced cough may occur in one-fourth of primary care prescriptions

Dry cough may affect a quarter of Malay patients initiated on angiotensin-converting enzyme inhibitors (ACEi), according to a new study.

In a retrospective review of electronic medical records of patients prescribed ACEi at a government primary care clinic throughout 2015 (n=394), researchers found that 24.1 percent (n=95) of patients developed cough after ACEi initiation, with 10.7 percent (n=42) developing cough on the same day as drug initiation, and 12.7 percent (n=50) within the first week thereafter. [Malays Fam Physician 2022;17(1):66–70]

The study population was primarily Malay (n=369), with a slight majority of men over women (n=225). Almost all were hypertensive (n=376), with many also diabetic (n=192).

In terms of ACEi types received, 98 percent of patients (n=386) were initiated on perindopril, with the remainder on perindopril/indapamide, captopril, or enalapril.

“As ACEi-induced cough is one of the differential diagnoses of chronic cough, it is important for physicians to recognise this phenomenon to avoid unnecessary investigation and treatment in patients treated with ACEi,” noted the study authors.

An additional finding of concern was that 92 of 95 patients who experienced ACEi-induced cough discontinued their prescription. The study authors recommended that physicians conduct follow-ups for patients initiated on ACEi at 1 week after initiation to identify possible cough development that could affect their adherence to therapy.

“The decision to discontinue ACEi therapy could then be decided cooperatively by the patient and doctor, taking into consideration the indications and benefits of the therapy and the patient’s tolerance to cough,” they added.

A common complication
ACEi are often used in hypertension and diabetes treatment as a first-line therapy based on treatment guidelines. They are widely prescribed in Malaysia due to the high prevalence of both conditions among the adult population.

However, adverse effects such as dry cough are not uncommon and can lead to nonadherence or withdrawal from therapy. While the mechanism of induction is unclear, the dry cough is likely related to drug-induced degradation of protussive mediators, leading to accumulation in the upper respiratory tract and throat irritation.

According to the study authors, reports from other countries estimate ACEi-induced cough occurs in 5–30 percent of patients who start ACEi. There have been no previous studies on incidence rates among Malaysian patient populations, although a Singaporean cohort study reported a 30.4 percent incidence rate among ethnic Chinese patients. [Singapore Med J 2014;55(3):146–149]

“Our study population was mostly of the Malay ethnic group, in which the incidence of ACEi-induced cough has not been previously reported,” remarked the authors.

The study also aimed to examine possible impact of age, gender, and ethnicity on the incidence of ACEi-induced cough. They found no association between those factors and cough incidence, though the researchers acknowledged that in the case of ethnicity, the study cohort was too small to be determinate.

Notably, while a total of 1,091 patients were initiated on ACEi at the clinic during the study period, two-thirds were excluded due to issues with follow-up and data retrieval. The researchers also acknowledged the limitations of a single-centre study and recommended further prospective studies with more diverse population samples and data from private clinics.