Hypertension

Hypertension impacts more than 50 million people in the US and over 1 billion people worldwide. The aging of the population increases the risk of hypertension such that hypertension is likely to represent the single most common chronic condition. The relationship between high blood pressure and the risk of cardiovascular disease is continuous, consistent, and independent of all other risk factors. A recent meta-analysis found that even a small increase in systolic blood pressure could result in 20% higher stroke mortality and 12% higher mortality from ischemic heart disease (Lewington 2002).

The aggressive management of elevated blood pressure has consistently been shown to reduce the rates of stroke, heart attack, and heart failure. Despite the variety of blood pressure reducing agents and their use in combinations, a recent National Health and Nutrition Examination Survey showed that only one third of treated patients achieve targeted blood pressure control.

A major reason for failure to achieve target blood pressure in patients with known high blood pressure is the high rate of discontinuation of or change in medication. The majority of treatments are changed or discontinued within the first 6 months in most medical practices, likely reflecting a combination of adverse drug effects, poor efficacy, and a lack of understanding of target organ damage. AR9281 offers a first-in-class anti-hypertensive agent with end organ protection and anti-inflammatory properties.

Metabolic Syndrome

Metabolic syndrome has been defined as a cluster of certain clinical conditions including visceral (abdominal) obesity, hyperglycemia (insulin resistance), dyslipidemia and elevated blood pressure and this disorder represents a significant risk factor for the development of cardiovascular disease and Type II diabetes mellitus. According to the National Heart Lung and Blood Institute, almost 25%, or about 47 million adults in the United States have metabolic syndrome, and the numbers are rapidly increasing with the “epidemic” of obesity. Insulin resistance (associated with Type II diabetes) is present in more than 20% of all patients with high blood pressure and more than 80% of Type II diabetics are hypertensive. Arête is exploring the utility of s-EH inhibitors for the treatment of metabolic syndrome.