Trandolapril: a newer angiotensin-converting enzyme inhibitor

Abstract

Background: Trandolapril is a newer angiotensin-converting enzyme (ACE) inhibitor that is approved by the US Food and Drug Administration for the treatment of hypertension and for use in stable patients who have evidence of left ventricular (LV) systolic dysfunction or symptoms of chronic heart failure within the first 2 days after an acute myocardial infarction (AMI). The fixed-dose combination of trandolapril and verapamil extended release (ER) is approved for the treatment of hypertension only.

Objective: The purpose of this article was to review the pharmacology, pharmacokinetics, clinical efficacy, and safety profile of trandolapril as monotherapy and in fixed-dose combination with verapamil ER.

Methods: Relevant studies were identified through a MEDLINE/PubMed search of the English-language literature published between January 1983 and August 2002 and a review of the bibliographies of identified articles.

Results: Trandolapril has a sufficient duration of inhibition of plasma ACE activity to allow once-daily dosing. It is converted by esterases to the active trandolaprilat metabolite, with mean terminal disposition half-lives of < 1 and approximately 75 hours for the prodrug and metabolite, respectively. In comparative trials in the management of hypertension, trandolapril 1 to 4 mg/d was statistically indistinguishable from or superior to captopril 100 mg/d, enalapril 10 or 20 mg/d, hydrochlorothiazide (HCTZ) 25 mg/d, nifedipine ER 30 or 40 mg/d, nitrendipine 20 mg/d, perindopril 4 mg/d, and verapamil ER 120 to 240 mg/d. In the Trandolapril Cardiac Evaluation, trandolapril also significantly reduced all-cause mortality, cardiovascular mortality, sudden death, and progression to severe chronic heart failure in patients with evidence of LV systolic dysfunction after AMI. In comparative trials in the management of hypertension, the combination of trandolapril 1 or 2 mg/d and verapamil ER 180 mg/d was statistically indistinguishable from or superior to the combinations of atenolol 50 or 100 mg/d plus chlorthalidone 12.5 or 25 mg/d, captopril 50 mg/d plus HCTZ 25 mg/d, lisinopril 20 mg/d plus HCTZ 12.5 mg/d, and metoprolol 100 mg/d plus HCTZ 12.5 mg/d. The most common adverse effects of trandolapril monotherapy in clinical trials of < or = 1 year's duration included cough, dizziness, and diarrhea (frequency < or = 1.9%). The most common adverse effects of trandolapril/verapamil ER therapy in clinical trials of < or = 1 year's duration included first-degree atrioventricular block, bradycardia, constipation, cough, diarrhea, dizziness, fatigue, and dyspnea (frequency < or = 4.6%). Based on the literature search, there are no published pharmacoeconomic evaluations of trandolapril alone or combined with verapamil ER in the US health care setting.

Conclusions: Based on the literature, trandolapril is a well-tolerated and effective antihypertensive agent, whether used alone or in combination with verapamil ER. These products may be valuable in patients with LV systolic dysfunction after AMI, although the combination product is approved for the management of hypertension only.