Potential Antithrombotic and Fibrinolytic Properties of the Angiotensin Converting Enzyme Inhibitors

Abstract

As a class of therapeutic agents, the ACE inhibitors have proven to have long-term mortality benefit when used after myocardial infarction and among patients with symptomatic congestive heart failure. Clinical trial data also indicate that the use of ACE inhibitors is associated with reduced rates of recurrent coronary thrombosis, an observation that raises the possibility that the renin-angiotensin system may be directly involved in the thrombotic process and that the ACE inhibitors may have valuable fibrinolytic and/or antithrombotic effects. Recent in vitro and in vivo studies of angiotensin II and its interactions with the fibrinolytic system, particularly with the primary inhibitor of intravascular fibrinolysis, plasminogen activator inhibitor type 1 (PAI-1), provide substantial support for this hypothesis. In addition, a series of cross-sectional studies have described a genetic linkage between a common ACE gene polymorphism (DD) and the prevalence of clinical cardiovascular events, an intriguing finding as this polymorphism may account for much of the population variability in plasma ACE levels. Taken together, the totality of available clinical and experimental findings support the possibility of a direct linkage between the ACE system and vascular thrombosis that merits further prospective evaluation.