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Trandolapril. An update of its pharmacology and therapeutic use in cardiovascular disorders
D C Peters1, S Noble, G L Plosker
1Adis International Limited, Auckland, New Zealand. demail@adis.co.nz
Insights
Trandolapril, an ACE inhibitor, effectively controls hypertension and reduces mortality in post-myocardial infarction patients with LV dysfunction. It offers a favorable safety profile, comparable to other ACE inhibitors.
Area of Science:
- Pharmacology
- Cardiology
Background:
- Trandolapril is an oral angiotensin-converting enzyme (ACE) inhibitor.
- It is used for hypertension, congestive heart failure (CHF), and post-myocardial infarction (MI).
- Trandolapril is a prodrug converted to active trandolaprilat.
Purpose of the Study:
- Evaluate trandolapril's efficacy in hypertension management.
- Assess its impact on mortality in post-MI patients with left ventricular (LV) dysfunction.
- Investigate its role in patients with CHF.
Main Methods:
- 24-hour ambulatory blood pressure monitoring to assess BP control.
- Analysis of data from the Trandolapril Cardiac Evaluation (TRACE) study for mortality outcomes.
- Comparison with other ACE inhibitors like enalapril.
Main Results:
- Trandolapril 2 mg daily provides >50% BP reduction over 24 hours in mild to moderate hypertension.
- Efficacy is comparable to enalapril.
- TRACE study showed a significant reduction in all-cause mortality (RR 0.78) in post-MI patients with LV dysfunction.
- Combined therapy with verapamil enhanced antihypertensive effects.
Conclusions:
- Trandolapril offers favorable pharmacology and antihypertensive efficacy comparable to other ACE inhibitors.
- Provides effective 24-hour BP control with once-daily dosing.
- Demonstrates long-term mortality protection in post-MI patients with LV dysfunction.
- Represents an effective, well-tolerated treatment for hypertension and post-MI LV dysfunction.
Unlabelled:
Trandolapril is an orally administered angiotensin converting enzyme (ACE) inhibitor that has been used in the treatment of patients with hypertension and congestive heart failure (CHF), and after myocardial infarction (MI). Trandolapril is a nonsulfhydryl prodrug that is hydrolysed to the active diacid trandolaprilat. Trandolapril 2 mg once daily provides effective control of blood pressure (BP) over 24 hours in patients with mild to moderate hypertension, with a trough/peak ratio of BP reduction (as determined by 24-hour ambulatory monitoring) consistently > or = 50%. Trandolapril has similar antihypertensive efficacy to enalapril as indicated by several clinical trials. Combined therapy with trandolapril and sustained-release verapamil has a significantly greater antihypertensive effect than either agent alone. Only limited data are available on the use of trandolapril in patients with CHF, although ACE inhibitors as a class are recommended as first line therapy in such patients. In the Trandolapril Cardiac Evaluation (TRACE) study, trandolapril 1 to 4 mg once daily resulted in an early and long term reduction in all-cause mortality, including cardiovascular mortality, in patients with left ventricular (LV) dysfunction after an MI. Trandolapril therapy was commenced a mean 4.5 days after acute MI and continued for 24 to 50 months. At study end, the relative risk of death from any cause with trandolapril versus placebo was 0.78 (p = 0.001). The tolerability profile of trandolapril is similar to that of other ACE inhibitors. Most adverse events are mild and transient in nature, and include cough, asthenia, dizziness, headache and nausea. Trandolapril has no adverse effect on lipid or carbohydrate metabolism.
Conclusions:
trandolapril has a favourable pharmacological profile and an antihypertensive efficacy at least comparable to that of other ACE inhibitors. The pharmacological characteristics of trandolapril allow it to provide good 24-hour control of BP with once-daily administration. Trandolapril has also demonstrated some efficacy in a small number of patients with CHF. In addition, trandolapril provides long term protection against all-cause mortality in patients with LV dysfunction after MI. The results of the Prevention of Events with Angiotensin Converting Enzyme Inhibition (PEACE) study will determine its potential as a cardioprotective agent in patients with coronary artery disease and preserved LV function. Thus, trandolapril represents an effective, well-tolerated and convenient treatment option for patients with mild to moderate hypertension or LV systolic dysfunction after MI.