Update on the use of trandolapril in the management of cardiovascular disorders

Abstract

Trandolapril is a well known angiotensin converting enzyme (ACE) inhibitor with many cardiovascular (CV) indications. The objectives of this article are to review the pharmacokinetics and pharmacodynamics properties of trandolapril and to focus on its clinical relevance in cardiovascular medicine. Various populations have been studied in large clinical trials including patients with congestive heart failure (CHF) after an acute myocardial infarction (AMI), diabetics, patients with hypertension (HTN), stable coronary artery disease (CAD) and prevention of proteinuria. Long-term treatment with trandolapril in patients with reduced left ventricular function soon after AMI significantly reduced the risk of overall mortality, mortality from CV causes, sudden death, and the development of severe CHF. Treatment with trandolapril after AMI complicated by left ventricular dysfunction appears to be of considerable importance in patients with diabetes mellitus by saving lives and substantially reducing the risk of progression to severe CHF as well. Moreover, trandolapril reduces progression to proteinuria in high-risk patients. Some of the advantages of trandolapril over other ACE inhibitors are the wide spectrum of patient populations studied, the well established dosage and its proven trough-to-peak effect ratios permitting a safe once-a-day administration.

Keywords: angiotensin converting enzyme inhibitors; diabetic nephropathy; hypertension cardiovascular diseases; trandolapril.

Figure 1

Renin-angiotensin-aldosterone system and site of action of different drugs that block the system as well as bradykinin by-products. Abbreviations: ACE, angiotensin-converting enzyme; AT₁, angiotensin II type I; EDHF, endothelium-derived hyperpolarizing factor; SNS, sympathetic nervous system.

Figure 2

Cumulative mortality from all causes among patients receiving trandolapril or placebo. Reprinted with permission from Kober L, Torp-Pedersen C, Carlsen JE, et al 1995. A clinical trial of the angiotensin-converting-enzyme inhibitor trandolapril in patients with left ventricular dysfunction after myocardial infarction. Trandolapril Cardiac Evaluation (TRACE) Study Group. N Engl J Med, 333:1670–6. Copyright © 1995 Massachusetts Medical Society. All rights reserved.

Figure 3

Event rates for the secondary end points of death from cardiovascular causes, sudden death, reinfarction and severe or resistant heart failure among patients receiving trandolapril or placebo. Reprinted with permission from Kober L, Torp-Pedersen C, Carlsen JE, et al 1995. A clinical trial of the angiotensin-converting-enzyme inhibitor trandolapril in patients with left ventricular dysfunction after myocardial infarction. Trandolapril Cardiac Evaluation (TRACE) Study Group. N Engl J Med, 333:1670–6. Copyright © 1995 Massachusetts Medical Society. All rights reserved.

Figure 4

Cumulative mortality from all causes in the trandolapril group compared with the placebo group over 10 years of follow-up. Reprinted with permission from Buch P, Rasmussen S, Abildstrom SZ, et al 2005. The long-term impact of the angiotensin-converting enzyme inhibitor trandolapril on mortality and hospital admissions in patients with left ventricular dysfunction after a myocardial infarction: follow-up to 12 years. Eur Heart J, 26:145–52. Copyright © 2005 European Society of Cardiology.

Figure 5

Cumulative mortality from all causes for patients with (A) and without (B) diabetes receiving trandolapril or placebo. Reprinted with permission from Gustafsson F, Torp-Pedersen C, Kober L, et al 1997. Effect of angiotensin converting enzyme inhibition after acute myocardial infarction in patients with arterial hypertension. TRACE Study Group, Trandolapril Cardiac Event. J Hypertens, 15:793–8. Copyright © 1997 Lippincott Williams & Wilkins.

Figure 6

Cumulative incidence of primary endpoint, according to treatment allocation. Reprinted with permission from Braunwald E, Domanski MJ, Fowler SE, et al 2004. Angiotensin-converting-enzyme inhibition in stable coronary artery disease. N Engl J Med, 351:2058–68. Copyright 2004 © Massachusetts Medical Society. All rights reserved.

Figure 7

Comparisson of outcomes in the PEACE trial and HOPE.

Figure 8

Kaplan–Meier Curves for the Percentages of Subjects with Microalbuminuria during Treatment with or without ACE Inhibitors (Panel A) and with or without Non-Dihydropyridine Calcium-Channel Blockers (Panel B). The difference between the group that received ACE inhibitor therapy and the group that did not, adjusted for prespecified baseline covariates (see text) was significant (p < 0.001) according to the accelerated failure-time model. The difference between the group that received non-dihydropyridine calcium-channel blockers and the group that did not was not significant (p = 0.92). Reprinted with permission from Ruggenenti P, Fassi A, Ilieva AP, et al 2004. Preventing microalbuminuria in type 2 diabetes. N Engl J Med, 351:1941–51. Copyright 2004 © Massachusetts Medical Society. All rights reserved.