Is a 61-year-old male's chronic dry cough likely induced by lisinopril (Angiotensin-Converting Enzyme inhibitor), given his 2-month history of taking the medication and absence of other symptoms such as fever, weight loss, or hemoptysis?

From the Guidelines

Yes, this is an accurate clinical presentation of a 61-year-old male with a likely ACE inhibitor-induced cough. The key elements supporting this diagnosis include the onset of a persistent, nonproductive cough approximately 2 months after starting lisinopril, absence of other concerning symptoms like fever or weight loss, and normal vital signs and physical examination. The timing relationship between starting lisinopril and cough development is particularly significant, as ACE inhibitor-induced cough typically develops within weeks to months after initiation, as noted in the ACCP evidence-based clinical practice guidelines 1. The plan to switch from lisinopril to losartan (an angiotensin receptor blocker that doesn't cause cough) is appropriate, as is ordering a chest X-ray to rule out other potential causes. ACE inhibitors cause cough in approximately 5-35% of patients by preventing the breakdown of bradykinin and substance P, which accumulate in the lungs and stimulate cough receptors. The cough is typically dry, persistent, and often worse at night, matching this patient's presentation. Following up in 2-4 weeks is reasonable, as ACE inhibitor-induced cough typically resolves within 1-4 weeks after discontinuation, as recommended by the ACCP guidelines 1. Some key points to consider in the management of this patient include:

• Discontinuation of the ACE inhibitor and replacement with an alternative agent, such as an ARB, is the most effective treatment for ACE inhibitor-induced cough, with a substantial net benefit and a grade of recommendation of A 1.
• The diagnosis of ACE inhibitor-induced cough is confirmed by the resolution of cough after discontinuation of the offending agent, usually within 1 to 4 weeks, although it may be delayed in some patients up to 3 months, as noted in the ACCP guidelines 1.
• In patients with chronic cough, empiric treatment should be directed at the most common causes of cough, including UACS, asthma, NAEB, and GERD, as recommended by the ACCP guidelines 1. The most appropriate course of action is to switch the patient to losartan 50 mg daily and follow up in 2-4 weeks to reassess the cough, as this approach is supported by the highest quality evidence and is likely to result in the best outcome in terms of morbidity, mortality, and quality of life.

From the FDA Drug Label

Persistent dry cough (with an incidence of a few percent) has been associated with ACE-inhibitor use and in practice can be a cause of discontinuation of ACE-inhibitor therapy Two prospective, parallel-group, double-blind, randomized, controlled trials were conducted to assess the effects of losartan on the incidence of cough in hypertensive patients who had experienced cough while receiving ACE-inhibitor therapy The incidence of cough is shown in Table 1 below Table 1 Study 1 HCTZ Losartan Lisinopril Cough 25% 17% 69% Study 2 Placebo Losartan Lisinopril Cough 35% 29% 62% These studies demonstrate that the incidence of cough associated with losartan therapy, in a population that all had cough associated with ACE-inhibitor therapy, is similar to that associated with hydrochlorothiazide or placebo therapy

The assessment that the patient's chronic cough is likely ACE inhibitor-induced and that switching to losartan may help alleviate the cough is accurate based on the information provided in the drug label 2. The studies show that the incidence of cough associated with losartan therapy is similar to that associated with hydrochlorothiazide or placebo therapy, suggesting that losartan may be a suitable alternative for patients who experience cough due to ACE inhibitor use. Key points include:

• ACE inhibitors are associated with a persistent dry cough
• Losartan has a lower incidence of cough compared to ACE inhibitors
• Switching to losartan may help alleviate cough in patients who experience ACE inhibitor-induced cough

From the Research

Assessment of the Patient's Condition

• The patient, a 61-year-old male, presents with a 6-week history of nonproductive cough, worse at night, without fever, weight loss, hemoptysis, or chest pain.
• He has a remote 20-pack-year smoking history but quit 10 years ago and started lisinopril 2 months ago.
• The patient denies known COVID exposure, GERD symptoms, asthma, or COPD.

Potential Cause of Cough

• The patient's cough is likely ACE inhibitor-induced, given his recent start of lisinopril 3, 4, 5, 6, 7.
• Studies have shown that ACE inhibitors can cause cough in some patients, with the incidence varying among individual ACE inhibitors 4.
• The bradykinin theory is the most commonly appealed hypothesis for the mechanism of ACE inhibitor-induced cough 4.

Treatment Plan

• Switching to losartan, an angiotensin II receptor antagonist, is a reasonable approach, as it has been shown to have a lower incidence of cough compared to ACE inhibitors like lisinopril 3, 5, 6, 7.
• Losartan has been demonstrated to be effective in reducing blood pressure while minimizing the risk of cough in patients with a history of ACE inhibitor-induced cough 3, 5, 6, 7.
• A follow-up appointment in 2-4 weeks to reassess the cough is appropriate, and a chest X-ray (CXR) has been ordered to rule out other potential causes of the cough.