Randomized Double-Blind Placebo-Controlled Study of Pyrazinoylguanidine Hydrochloride (Amiloride) in Subjects With Coronary Artery Disease

Treatment of Cardiovascular Diseases (CVD) is a major health care problem across the entire word, and particularly in the United States. In fact, these life-threatening disorders are a major cause of emergency medical care and hospitalization in the United States, and according the National Center for Health Statistics (NCHS) there were approximately 1,565,000 hospitalizations for primary or secondary diagnosis of an acute coronary syndrome (ACS), 669,000 for unstable angina (UA) and 896,000 for myocardial infarction (MI). In the 2003, NCHS reported 4,497,000 visits to emergency departments for primary diagnosis of CVD, wherein the average age of a person having a first heart attack is calculated at 65.8 years for men and 70.4 years for women.

Further studies provided by the Heart Disease and Stroke Statistics-2007 Update, of the American Heart Association, reported an estimated 79 400 000 American adults (1 in 3) have 1 or more types of CVD. Of these, and 37 500 000 are estimated to be age 65 or older. As a separate diagnosis, high blood pressure or hypertension, accounts for approximately 72 000 000 of patients (defined as systolic pressure 140 mm Hg or greater and/or diastolic pressure 90 mm Hg or greater, taking antihypertensive medication), coronary heart disease (CHD) for approximately 15 800 000 patients, myocardial infarction for approximately 7 900 000 patients, and angina pectoris (chest pain secondary to ischemic heart disease) for approximately 8 900 000 patients.

Although the treatment of angina (chest pain secondary to ischemic heart disease and one of the most common and early symptom of coronary artery disease) can be tracked as far as 1880's, it still represents a medically unresolved problem. Indeed, treatment of angina in particular, as well as associated condition as ACS, UA, and MI, involves a large number of life-style change recommendations, dietetic advice, drugs, coronary artery intervention, or coronary bypass surgery aimed to improve symptoms, quality of life of patients, and even primary or secondary prevention of the CVD. Unfortunately, despite a century of medical advances and epidemiological studies, the current approach to CVD, and coronary artery disease remain complex, and at times frustrating.

Among some of the proposals to combat CVD, have included the single "polypill"(aspirin + statin + 3 blood pressure lowering agents in half dose, and folic acid) as a strategy to reduce CVD by more than 80% remains presently unresolved, regression of coronary atherosclerosis by using Simvastatin and intravascular ultrasound study was determined to be unpractical. It remains to be determined whether these changes will translate to meaningful reductions in clinical events, or whether new antithrombotic agents for these CVD patients can provide an adequate solution. However, the overarching determination in view of the purported successes to date remains whether these results in highly selected patient populations can be matched to the real-world treatment of acute coronary syndromes.

In a recent study called the COURAGE Trial (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) conducted in 50 hospital centers across the United States and Canada showed that optimal drug treatment with percutaneous coronary interventions (PCI) for stable coronary artery disease, was not more effective than optimal medical therapy alone for preventing cardiovascular events, hospitalization or death, suggesting that drugs, surgical procedures or both were not a statistically effective solution for CHD.