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Evaluating Lipid-Lowering Therapies


Eileen Koutnik-Fotopoulos

New Orleans—One in 3 Americans die of cardiovascular disease (CVD), and individuals are at higher risk for atherosclerosis and CVD if they have elevated levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, apolipoprotein B, or non−high-density lipoprotein (HDL) cholesterol and low levels of HDL cholesterol.

During a session at the CRS meeting, Karol E. Watson, MD, PhD, assistant professor of medicine, David Geffen School of Medicine, University of California, Los Angeles, summarized the American College of Cardiology/American Heart Association 2013 cholesterol guidelines and discussed statin efficacy and safety for lowering LDL cholesterol in reducing cardiovascular risk.

Cholesterol Guidelines
Dr. Watson said the general principles of the guidelines are [J Am Coll Cardiol. 2014;63(25 Pt B):2889-2934]:
• All adults should adhere to a healthy lifestyle, which is the foundation for cardiovascular health
• Statin therapy is recommended for adults in groups demonstrated to benefit, including adults with clinical atherosclerotic cardiovascular disease (ASCVD), adults with LDL cholesterol ≥190 mg/dL, adults with diabetes, and adults with an estimated 10-year ASCVD risk ≥7.5%
• Engage in a clinician–patient discussion prior to initiating statin therapy, especially for primary prevention in patients with low ASCVD risk
• Current evidence inadequately supports treatment specific to LDL
cholesterol and/or non-HDL cholesterol goals
• Initiate the appropriate intensity of statin therapy

In addition, the following misconceptions about the guidelines were highlighted, followed by insight from Dr. Watson on each:
All patients with a 10-year CVD risk ≥7.5% must be treated with a statin. Dr. Watson said the guidelines emphasize patient–provider discussion
There is no longer a role for rechecking lipids. Dr. Watson explained that lipids should be rechecked at 4 to 12 weeks to verify therapeutic response and to monitor adherence; lipid rechecks should occur every 3 to 12 months
There is no role for nonstatin therapy. Dr. Watson countered that there remains a role for add-on therapy at the provider’s discretion in high-risk patients
The new risk algorithm overhauls the Framingham Risk Score, incorporating new risk markers into the calculation of 10-year CVD risk. Dr. Watson noted that the new risk estimator includes the Framingham Risk Score along with 3 other cohorts that add power and diversity

Statin Efficacy and Safety
Statins are considered the first-line treatment in reducing cardiovascular risk. The efficacy of statin therapy has been widely reported. Dr. Watson highlighted a prospective meta-analysis of data from 90,056 individuals in 14 randomized trials of statin therapy. Reported in Lancet in 2005, Baigent et al concluded that statin therapy can safely reduce the 5-year incidence of major coronary events, coronary revascularization, and stroke by about one-fifth per mmol/L reduction in LDL cholesterol. However, lately the safety of statins has come under scrutiny, with a focus on liver damage, muscle weakness, cognitive effects, and increased risk of cancer and diabetes.

Dr. Watson said based on the evidence, liver damage due to statins is extremely rare. Statins can produce muscle pain and weakness, but the risk of true rhabdomyolysis is very small. Clinical trials have found no evidence of cognitive impairment and evidence of cancer with statins. Statins can increase blood glucose level, minimally leading to increased reports of diabetes. “In most patients at risk for CVD, the benefits of statins far outweigh the risks,” Dr. Watson said.

Hypertriglyceridemia and Emerging Treatment Strategies
Hypertriglyceridemia, a type of dyslipidemia, is defined as elevated triglyceride concentration in the blood, referring to levels >150 mg/dL, according to the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). It is associated with increased cardiovascular risk.
Michael Miller, MD, FACC, FAHA, professor of epidemiology, medicine, and public health, University of Maryland School of Medicine, discussed hypertriglyceridemia and emerging treatment therapies.

There are 4 causes of hypertriglyceridemia, which are divided into 2 categories: primary and secondary. Genetic or familial hypertriglyceridemia is referred to as primary hypertriglyceridemia. Dr. Miller noted that there are numerous secondary causes of hypertriglyceridemia, such as diabetes, alcohol use, obesity, pregnancy, and medications, especially steroids, protease inhibitors, and antipsychotic medications. Treatment options for dyslipidemia include statins, bile acid sequestrants, nicotinic acid, fibrates, cholesterol absorption inhibitors, and prescription omega-3 medications.

Dr. Miller reviewed the effects of lipid-lowering therapies on triglyceride reduction. He reported that data has shown a 30% to 50% reduction with fibrates, a 20% to 50% reduction with the nicotinic acid, niacin, a 10% to 40% reduction with omega-3 medications, a 10% to 30% reduction with statins, and a 5% to 10% reduction with the cholesterol absorption inhibitor, ezetimibe.

Dr. Miller highlighted the prescription omega-3-acid ethyl esters. He explained that omega-3-acid ethyl esters are a combination of ethyl esters of omega-3-fatty acids containing 465 mg eicosapentaenoic acid and 375 mg docosahexaenic acid in a 1 g capsule. The medication is FDA approved as an adjunct to diet to reduce triglyceride levels for adult patients with severe (500 mg/dL) hypertriglyceridemia. The daily dose of omega-3-acid ethyl esters is 4 g per day taken as a single 4 g dose or as a 2 g dose taken twice daily.

Data has shown that omega-3 fatty acids are a safe and effective therapy for triglyceride-lowering in hypertriglyceridemic patients, according to Dr. Miller. “Ongoing clinical trials will assess whether combination therapy is clinically superior to statin therapy in the treatment of hypertriglyceridemia,” he said.—Eileen Koutnik-Fotopoulos

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