High-Risk Cardiovascular Disease
Acute Coronary Syndrome (ACS)
Acute coronary syndrome (ACS) is a term used for any condition brought on by sudden, reduced blood flow in the coronary arteries, such that part of the heart muscle is unable to function properly or dies. ACS symptoms may include the type of chest pressure felt during a heart attack, or pressure in the chest while at rest or doing light physical activity (unstable angina). The first sign of ACS can be sudden stopping of the heart (cardiac arrest).
Major Adverse Cardiac Events (MACE)
Major Adverse Cardiac Events (MACE) refers to adverse events caused by cardiovascular disease (CVD) processes generally affecting the coronary arteries. It is the strongest outcome measure for providing prognostic predictability for CVD. MACE is the most impactful marker of CVD according to physicians and CVD Key Opinion Leaders. MACE includes a variety of cardiovascular outcomes such as cardiovascular mortality, myocardial infarction and stroke and can also include hospitalizations for acute coronary syndromes (worsening angina) and urgent revascularization procedures (such as percutaneous stent procedures and coronary artery bypass grafting).
According to the 2015 American Heart Association Statistics report, based on 2011 death rate data, over 2,150 Americans die of CVD each day, an average of 1 death every 40 seconds. Many of these CVD patients will have some form of MACE during or after they have been diagnosed with CVD. Although CVD has many current therapeutic agents that are utilized including lipid lowering drugs such as statins, heart rate lowering agents such as beta blockers, blood pressure lowering drugs such as ACE inhibitors, there still remains a large residual risk of MACE in patients that take all of these current medicines. CVD and MACE remain a major cause of mortality and morbidity in North America. According to the 2015 American Heart Association Statistics report, more than 85 million Americans have one or more vascular diseases. By the year 2030 the total projected economic burden and direct costs of CVD in the United States is estimated at $918 billion annually.
Diabetes Mellitus (DM)
Diabetes Mellitus (“DM”) is a serious disease for which there is currently no known cure. 68% of people over the age of 65 with diabetes will die from cardiovascular disease. It is the most common metabolic disease that affects humans and currently is a worldwide epidemic fueled by the wave of modernization spreading across much of third world societies.
Based on clinical analysis, Apabetalone or RVX-208 treatment appears to affect several parameters pointing to potential benefits in DM. The first parameter is major adverse cardiovascular events (MACE) in the DM population. In the ASSURE study, the diabetic population was a pre-specified subgroup and RVX-208 treatment resulted in a 74% relative risk reduction in MACE. In the analysis of combined data of both the ASSURE and SUSTAIN studies, the relative risk reduction of MACE in the DM population was also 77%. An additional analysis showed that patients with DM given RVX-208 tended to have lower blood glucose vs. placebo. However, specifically in patients with DM who had low HDL, the blood glucose was significantly lower following treatment with RVX-208 vs. placebo. It should be noted that the time required for RVX-208 to reduce blood glucose was not observed until at least 12 weeks following initiation of treatment.
Chronic Kidney Disease (CKD)
40% of people suffering from DM will eventually develop chronic kidney disease (CKD). CKD results from the long term effects of DM on blood vessels and the filtration apparatus (nephrons) of the kidneys. It is often referred to as a silent killer because it is insidious in onset, progressing slowly over many years and sometimes decades. According to the National Institute of Diabetes and Digestive and Kidney Diseases, more than 31 million people in the US (or 10% of the adult population) currently suffer from CKD.
Healthy kidneys filter metabolic by-products from the blood which are then eliminated from the body in the form of urine. One important measure of kidney function is estimated glomerular filtration rate (eGFR) which assesses the amount of fluid the kidney can filter over a period of time. In patients with CKD, as kidney function declines, the eGFR decreases, and can eventually lead to kidney failure resulting in end-stage renal disease (ESRD). These patients require hemodialysis, often multiple times per week, in which a machine removes the metabolic waste products from the blood. The cost of ESRD and hemodialysis to the healthcare system is enormous, exceeding $34 billion each year in the U.S. The cost for one patient to be on dialysis for one year is almost $90,000.
In patients with mild to moderate CKD (as reflected by a reduced eGFR), treatment with RVX-208 appeared to stabilize filtration rates. Additionally, alkaline phosphatase (ALP), an enzyme that is produced in several tissue types that has been linked to the kidney, is lowered by the actions of RVX-208. This finding is significant because, in the CKD population, ALP is one of the best biomarkers of not only CVD but also total mortality.