What is the best antihypertensive medication for a patient with a chronic cough, considering alternatives to lisinopril (Angiotensin-Converting Enzyme inhibitor)?

From the Guidelines

For a patient with hypertension and chronic cough who cannot take lisinopril, an angiotensin II receptor blocker (ARB) such as losartan (50-100 mg daily) is the best alternative. This recommendation is based on the evidence that ARBs provide similar blood pressure control to ACE inhibitors but have a significantly lower risk of causing cough, as they block the angiotensin II receptor directly rather than inhibiting the ACE enzyme, which prevents the accumulation of bradykinin that typically causes the dry cough associated with ACE inhibitors like lisinopril 1.

Key Points to Consider

• The incidence of ACE inhibitor-induced cough has been reported to be in the range of 5 to 35% among patients treated with these agents, but the incidence of cough associated with therapy with angiotensin-receptor blockers appears to be similar to that of the control drug 1.
• The only uniformly effective treatment for ACE inhibitor-induced cough is the cessation of treatment with the offending agent, and switching to an ARB is a recommended alternative 1.
• Other good alternatives include calcium channel blockers like amlodipine (5-10 mg daily) or thiazide diuretics such as hydrochlorothiazide (12.5-25 mg daily), both of which are effective antihypertensives that don't cause cough.
• When switching from lisinopril to an ARB, no washout period is necessary, and the new medication can be started the day after discontinuing the ACE inhibitor, with close monitoring of blood pressure during the first few weeks after switching medications to ensure adequate control is maintained.

Management of Cough

In patients presenting with chronic cough, it is essential to determine if the ACE inhibitor is the cause of the cough, and therapy with ACE inhibitors should be discontinued regardless of the temporal relation between the onset of cough and the initiation of ACE inhibitor therapy 1. The diagnosis is confirmed by the resolution of cough, usually within 1 to 4 weeks of the cessation of the offending agent. In patients whose cough resolves after the cessation of therapy with ACE inhibitors, and for whom there is a compelling reason to treat with these agents, a repeat trial of ACE inhibitor therapy may be attempted 1.

From the FDA Drug Label

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 Cases of cough, including positive re-challenges, have been reported with the use of losartan in postmarketing experience. 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%

Losartan vs Lisinopril in a patient with chronic cough:

• Losartan has a lower incidence of cough compared to lisinopril in patients who had experienced cough while receiving ACE-inhibitor therapy.
• The incidence of cough with losartan is similar to that associated with hydrochlorothiazide or placebo therapy.
• Losartan may be a better alternative to lisinopril in patients with a chronic cough, as it has a lower incidence of cough. 2

From the Research

Comparison of Losartan and Lisinopril in Patients with Chronic Cough

• Losartan, an angiotensin II receptor antagonist, has been shown to have a lower incidence of cough compared to lisinopril, an angiotensin-converting enzyme (ACE) inhibitor, in patients with a history of ACE inhibitor-induced cough 3, 4, 5.
• Studies have demonstrated that the incidence of cough with losartan is significantly lower than with lisinopril, with rates ranging from 18% to 36.7% for losartan and 72% to 97% for lisinopril 3, 4, 5.
• The frequency of cough, as measured by visual analogue scale, is also lower for losartan compared to lisinopril 3, 4, 5.

Mechanism of Cough Induction

• ACE inhibitor-induced cough is believed to be related to the accumulation of bradykinin, substance P, and prostaglandins resulting from the inhibition of ACE 6.
• Losartan, as an angiotensin II receptor antagonist, does not inhibit ACE and therefore does not cause the accumulation of these substances, leading to a lower incidence of cough 6, 3, 4.

Clinical Implications

• Losartan may be a suitable alternative for patients with a history of ACE inhibitor-induced cough, as it has been shown to have a lower incidence of cough compared to lisinopril 3, 4, 5.
• However, it is essential to note that losartan can still cause cough in some patients, although the incidence is lower than with ACE inhibitors 6, 7.
• Further studies are needed to fully understand the mechanisms of cough induction and to determine the best treatment options for patients with chronic cough and hypertension 6, 3, 4, 7, 5.