Pharmacologic, Pharmacokinetic, and Therapeutic Differences among ACE Inhibitors

Abstract

Angiotensin‐converting enzyme (ACE) inhibitors are a heterogeneous group of agents, and important pharmacologic, pharmacokinetic, and therapeutic differences among them must be understood to obtain optimal therapy. For patients with severe liver disease, lisinopril and captopril are not prodrugs (e.g., do not require hepatic activation), and lisinopril has almost solely renal elimination. Enalaprilat, the intravenous formulation of enalapril, is the only intravenously available ACE inhibitor and can be given to patients with severe liver dysfunction as it is also not a prodrug. Fosinopril is the only drug with compensatory dual routes of elimination, and it does not require dosage adjustment in patients with reduced renal function, as other ACE inhibitors do. Captopril and moexipril have potential drug‐food interactions and are the only agents that should be spaced from meals. The ACE inhibitors also differ in their dialyzability, half‐life, lipophilicity, trough:peak ratios, approved indications, and therapeutic information available for many indications.

The Effects of a Perindopril-Based Regimen in Relation to Statin Use on the Outcomes of Patients with Vascular Disease: a Combined Analysis of the ADVANCE, EUROPA, and PROGRESS Trials

“…To the best of our knowledge, our study is the first sufficiently powered study to directly compare the benefits of an ACE inhibitor versus placebo in the context of statin therapy in a randomized fashion and therefore adds importantly to the current literature by showing a positive additive effect of a perindopril-based regimen. ACE inhibitors may differ from each other with regard to their pharmacokinetic and pharmacodynamic properties, but large head-to-head clinical trials comparing different ACE inhibitors have not been performed [ 45 – 47 ]. However, perindopril in particular is characterized by a long duration of action (24 h), high affinity for tissue ACE, and pronounced bradykinin potentiation, which has beneficial endothelial effects [ 48 ].…”

Enalapril Is Superior to Lisinopril in Improving Endothelial Function without a Difference in Blood–Pressure–Lowering Effects in Newly Diagnosed Hypertensives

“…These findings pinpoint vascular endothelium as the site of action for ACEi drugs. Therefore, the apparent class effect for ACEi drugs is rather surprising in light of marked differences in their pharmacokinetics [5], lipophilicities [14], and elimination pathways [14,15]. Here, we tested two drugs, originally developed by Merck [16].…”