Question

Describe how you would design a valid randomized controlled trial to test the hypothesis that Low-Chol, a new oral medication to lower serum cholesterol, decreases the risk of death from coronary heart disease in healthy men, 40-54 years of age, at high risk for the disease. Include in your description how you would select the study sample, determine the subject eligibility criteria, ascertain the appropriate sample size, allocate the subjects into experimental and control groups, apply the intervention, and assess the outcomes during follow-up.

Answer 1

Cardiovascular disease remains the leading cause of mortality and morbidity with coronary artery disease (CAD) being the number-one cause of death.Dyslipidemia is a major contributor to the development of CAD and other forms of atherosclerosis; individuals with high total cholesterol levels (≥240 mg/dL) have about twice the risk for heart disease. Approximately 100 million adults have total cholesterol levels >200 mg/dL (borderline high), and almost 74 million have high levels of low-density lipoprotein cholesterol (LDL-C). Adults aged >20 years should have their cholesterol measured at least once every 5 years.

There are many pharmacologic therapies to treat dyslipidemia, including HMG-CoA reductase inhibitors or statins, cholesterol absorption inhibitors, niacin, bile acid sequestrants, fibrates, and omega-3 fatty acids; however, statins are the mainstay of treatment. In 2013, the American College of Cardiology (ACC) and the American Heart Association (AHA) released guidelines for the treatment of blood cholesterol.Rather than providing specific cholesterol targets, the current guidelines focus on intensity of statin treatment in four different groups.This shift in treatment can potentially increase the number of adults who are eligible to take statins by 12.8 million.The National Lipid Association’s recommendations released in 2014 provide non–high-density lipoprotein cholesterol (non–HDL-C) goals, but like the ACC/AHA guidelines, treatment focuses on statins as the primary agent of choice.

Despite this, nearly half of treatment-eligible adults are not taking cholesterol-lowering drugs.This can be attributed to many reasons, including cost, perceived susceptibility to cardiovascular risks, and, most commonly, fear and concerns regarding safety and adverse effects.

Some of these patients may be looking for alternative ways to lower their cholesterol and reduce their risk for cardiovascular disease. About 34% of adults in the U.S. are using some form of complementary and alternative medicine (CAM). Cholesterol is included as one of the top 10 conditions for which adults are using CAM.Fish oil and garlic, two supplements commonly used for the reduction of high cholesterol, were among the top 10 most frequently used natural products.Pharmacists are in an ideal position to educate patients about the use of OTC products for the management of high cholesterol.

Supplements that are supported by clinical evidence and guidelines include immediate-release niacin, omega-3 fatty acids, and soluble fiber. Pharmacists should keep in mind, however, that these products are not regulated by the FDA and there may be inconsistencies between different manufacturers and batches. Pharmacists should also avoid recommending garlic, RYR, sustained-release niacin, no-flush niacin, and niacinamide due to lack of efficacy or documented adverse effects. A strong emphasis should be placed on the benefits associated with therapeutic lifestyle changes, such as maintaining a healthy weight, eating a low-fat, low-cholesterol, high-fiber diet, and exercising regularly. Patients should also be reminded to inform their healthcare providers of any supplements they may be taking.