Results of Trial with COZAAR in Patients with Acute Myocardial Infarction Presented at European Society of Cardiology

Business Wire, Sept 2, 2002

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. Patients who had typical ACE inhibitor cough when challenged with lisinopril, whose cough disappeared on placebo, were randomized to losartan 50 mg, lisinopril 20 mg, or either placebo (one study, n=97) or 25 mg hydrochlorothiazide (n=135). The double-blind treatment period lasted up to 8 weeks. The incidence of cough is shown below.

    Study 1                HCTZ              Losartan       Lisinopril
-------------------- ------------------ ------------------ -----------
     Cough                  25%                17%              69%

    Study 2               Placebo            Losartan       Lisinopril
-------------------- ------------------ ------------------- ----------
     Cough                  35%                29%             62%

      Demographics = (89% caucasian, 64% female)
       Demographics = (90% caucasian, 51% female)

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.

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

Post-Marketing Experience

The following additional adverse reactions have been reported in post-marketing experience:

Hypersensitivity: Angioedema, including swelling of the larynx and glottis, causing airway obstruction and/or swelling of the face, lips, pharynx, and/or tongue has been reported rarely in patients treated with losartan; some of these patients previously experienced angioedema with other drugs including ACE inhibitors. Vasculitis, including Henoch-Schonlein purpura, has been reported. Anaphylactic reactions have been reported.

Digestive: Hepatitis (reported rarely).

Respiratory: Dry cough (see above).

Hyperkalemia and hyponatremia have been reported.

Laboratory Test Findings

In controlled clinical trials, clinically important changes in standard laboratory parameters were rarely associated with administration of COZAAR.

Creatinine, Blood Urea Nitrogen: Minor increases in blood urea nitrogen (BUN) or serum creatinine were observed in less than 0.1 percent of patients with essential hypertension treated with COZAAR alone (see PRECAUTIONS, Impaired Renal Function).

Hemoglobin and Hematocrit: Small decreases in hemoglobin and hematocrit (mean decreases of approximately 0.11 grams percent and 0.09 volume percent, respectively) occurred frequently in patients treated with COZAAR alone, but were rarely of clinical importance. No patients were discontinued due to anemia.