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New Treatment Strategies Could Address Unmet Needs in Dyslipidemia Patients
Las Vegas, NV—New treatment strategies are being introduced for dyslipidemia patients with the greatest need, creating new treatment opportunities to overcome the limitations of conventional hyper-cholesterolemia therapies, according to a recent presentation during the CRS Fall.
Karol E. Watson, MD, PhD, FACC, professor of medicine and cardiology and co-director of the UCLA Program in Preventative Cardiology, led the session.
The American College of Cardiology and American Heart Association 2013 guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults emphasizes the use of statins. While helpful, some high-risk patients still have unmet needs.
Individuals who have the greatest un-met needs are those who are statin-resistant; are statin-intolerant; have familial hypercholesterolemia (FH); or have low high-density lipoprotein (HDL).
Statin resistance develops in some patients due the significant interpatient variability. Intolerance is also common, with an estimated prevalence of 2% to 20%.
It usually manifests as muscle pain, aches, or weakness, and often leads to noncompliance. However, Dr Watson noted that most patients can be successfully rechallenged with a statin.
More than 600,000 people in the US have FH, but only 10% are diagnosed. Dr Watson said clinicians should consider FH whenever the LDL-C is ≥ 190 mg/dL. Identifying patients is important because FH can cause early cardiovasular disease, and is also difficult to treat. Further, a high potency statin may not be enough. New treatment strategies—such as antisense oligonucleotide (ASO), microsomal trigylceride transport protein inhibition, PCSK9 inhibition, and cholesteryl ester transfer protein (CETP) inhibition—could help.
For instance, ipomersen, an apolipoprotein B (apoB) ASO, has been shown to reduce LDL when administered weekly, compared with a placebo. In addition, lomitapide, a microsomal triglyceride transfer protein (MTP) inhibitor that works by limiting the secretion of cholesterol and triglycerides from the intestine and liver, has also been shown to reduce LDL when administered daily.
Mipomersen and lomitapide carry list prices of $175,000 and $250,000 per year, respectively, he said.
Advancements are also being made with PCSK9 inhibitors, which could act well with other lipid lowering agents. PCSK9 levels have been found to increase when used with lipid-lowering agents such as statins, fenofibrate and ezetimibe, noted Dr Watson.
Low HDL is the most common risk factor in patients with premature coronary artery disease. Lifestyle measures—such as losing weight, eating a healthy diet, and exercising—have been found to be effective in increasing HDL.
Several trials of medications used for low HDL have been halted due to health concerns. A trial using high-dose extended release niacin in combination with a statin ended early because the drug offered no additional benefit but increased ischemic stroke. A trial of the CETP inhibitor torcetrapib also ended early due to an increased risk of death and cardiac events.
While safety has been a concern for some CETP inhibitors, phase 3 trials are ongoing for anacetrapib and evacetrapib, said Dr Watson.—Jill Sederstrom
