From the Guidelines
ACE inhibitor-induced cough is not dose-dependent, as stated in the most recent and highest quality study available 1. This side effect occurs in approximately 5-35% of patients taking ACE inhibitors such as lisinopril, enalapril, ramipril, and others. The cough develops because ACE inhibitors prevent the breakdown of bradykinin and substance P in the lungs, leading to local irritation. If a patient develops a troublesome cough while on an ACE inhibitor, several approaches can be taken:
- switching to another ACE inhibitor might help, though cross-reactivity is common;
- or changing to an angiotensin receptor blocker (ARB) like losartan or valsartan often resolves the issue completely as ARBs don't affect bradykinin metabolism, as recommended by the ACCP guidelines 1. The cough typically resolves within 1-4 weeks after discontinuing the ACE inhibitor, though it can occasionally persist longer. In patients in whom persistent or intolerable ACE inhibitor-induced cough occurs, therapy should be switched to an ARB, with which the incidence of associated cough appears to be similar to that for the control drug, or to an appropriate agent of another drug class, as recommended by the ACCP guidelines 1.
From the Research
ACE-I Cough Dependency on Dose
- The relationship between ACE-I dose and cough incidence is not clearly established in the provided studies.
- A study from 1994 2 found that cough was not dose-related in patients treated with enalapril, captopril, perindopril, or lisinopril.
- However, other studies do not provide direct evidence on the dose-dependency of ACE-I induced cough.
Variability in Cough Incidence Among ACE-Is
- The incidence of cough varies among individual ACE-Is, with some agents like perindopril associated with a lower rate of cough 3, 4.
- A systematic review and network meta-analysis 5 ranked the risk of cough induced by different ACE-Is, with moexipril having the highest risk and spirapril having the lowest risk.
- The study also found that all ACE-Is have a similar risk of developing a cough, suggesting that the incidence of cough is not solely dependent on the dose.
Management of ACE-I Induced Cough
- Temporary discontinuation of ACE-I and reintroduction after cough remission is a proposed strategy for managing ACE-I induced cough 3.
- Adding calcium channel blockers to ACE-Is or switching to alternative drugs like angiotensin receptor blockers may also be effective in managing cough 3, 4.
- The decision to switch or discontinue ACE-Is should be based on individual patient factors, including the severity of cough and the presence of other comorbidities.