A Review of Vasopeptidase Inhibitors
Vasopeptidase inhibitors are a group of agents capable of inhibiting neutral endopeptidase and angiotensin-converting enzymes, which leads to potentiation of natriuretic peptide actions and suppression of the renin-angiotensin-aldosterone system. With this distinctively characteristic mechanism, these agents have emerged as a new drug class for management of hypertension and heart failure. Several vasopeptidase inhibitors are under clinical investigation. Omapatrilat is the most studied agent in this class. Clinical studies of omapatrilat in hypertension have consistently shown the agent's effectiveness in a variety of patient populations. In patients with heart failure, omapatrilat significantly improved neurohormonal and hemodynamic status. Long-term effects of omapatrilat in patients with heart failure recently were compared with those of conventional therapy in a large phase II trial. Results of the study appear promising. Large clinical trials are ongoing, and additional information regarding safety and efficacy from these studies may help define the place in therapy for this agent.

Approximately 60 million Americans are affected by cardiovascular disease. Since the beginning of the 20th century, cardiovascular disease has consistently been the leading cause of death in the United States despite numerous advances in treatment. In 1998, approximately 1 million people died of cardiovascular disease. Hypertension and heart failure are the first and fifth most common causes of cardiovascular disease, affecting 50 million and 5 million Americans, respectively. The estimated economic burden resulting from hypertension and heart failure exceeds $60 billion/year. In addition, hypertension is the leading cause of heart failure and end-stage renal disease. Despite increased awareness and treatment of hypertension, only 27% of Americans with hypertension achieve modest control (blood pressure < 140/90 mm Hg), according to the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension is present in 75% of patients with heart failure, and from 1979-1998 heart failure deaths increased 135%.

In the past 2 decades, our understanding of the pathophysiology of hypertension and chronic heart failure has improved considerably. Discovered in the early 1980s, the natriuretic peptide (NP) system is now thought to play a crucial role in the pathogenesis of many cardiovascular diseases, including hypertension and heart failure. Agents targeted at various components of the NP system have been under investigation. Vasopeptidase inhibitors are one of the most promising categories of agents that may be introduced into clinical practice in the near future. Practitioners should become familiar with the importance of the NP system and with current information regarding the potential use of vasopeptidase inhibitors in the management of hypertension and heart failure.