Rev Cardiovasc Med
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Homozygous familial hypercholesterolemia (HoFH) is associated with severe hypercholesterolemia and premature cardiovascular morbidity and mortality. The most frequent cause of HoFH is loss of function mutations in the gene for the low-density lipoprotein receptor, resulting in reduced clearance of low-density lipoprotein (LDL) cholesterol from the circulation. ⋯ Lomitapide is a novel microsomal triglyceride transfer protein inhibitor that does not depend on the ability to upregulate LDL receptors on the surface of hepatocytes. Lomitapide reduces production of apolipoprotein B-containing lipoproteins, significantly reduces serum levels of LDL cholesterol, and is approved for use in patients with HoFH in the United States and the European Union.
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Review
The potential role of anti-PCSK9 monoclonal antibodies in the management of hypercholesterolemia.
Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death and disability in developed nations, and it is rising rapidly in other parts of the developing world. Levels of low-density lipoprotein cholesterol (LDL-C) are directly correlated with atherogenic risk, and statin-based therapy is the most common management for these patients. However, many patients exhibit resistance to and/or adverse effects from statin therapy, and there is a need for adjunctive therapies or statin alternatives for these patients. ⋯ Consequently, PCSK9 inhibition to reduce LDL-C levels has become a primary focus for drug development. Numerous clinical trials focusing on monoclonal antibodies against PCSK9 have demonstrated efficacy equal to or greater than statin therapy for lowering LDL-C levels. Long-term trials are underway to assess safety, tolerability, and ability to reduce ASCVD.
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Review Case Reports
Lomitapide for the management of homozygous familial hypercholesterolemia.
Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder of low-density lipoprotein cholesterol (LDL-C) metabolism resulting in extremely elevated serum levels of LDL-C and premature atherosclerotic cardiovascular disease. Treatment typically involves multiple pharmacologic agents, as well as mechanical filtration using weekly or biweekly LDL apheresis. Despite combination lipid-lowering therapy, LDL-C levels and cardiovascular morbidity and mortality remain unacceptably high in HoFH patients. ⋯ Lomitapide is an orally administered inhibitor of microsomal triglyceride transfer protein that is indicated as an adjunct to a low-fat diet and other lipid-lowering treatments, including LDL apheresis where available for the reduction of LDL-C, total cholesterol, apolipoprotein B, and non-high-density lipoprotein cholesterol in adult patients with HoFH. The risks of transaminase elevations, hepatic steatosis, and gastrointestinal side effects, and the potential for drug interactions, require vigilant examination of the clinical and laboratory data and patient counseling prior to initiation of lomitapide, as well as regular monitoring during follow-up care. This article highlights important practical considerations for the use of lomitapide in the context of the evaluation and management of a HoFH patient case.
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Despite the variety of antihypertensive agents that are available, resistant hypertension remains a significant clinical problem and a substantial economic burden. Over the past several years, renal sympathetic denervation has been introduced as a potential therapeutic option for this clinical problem. ⋯ Thus far, two completed clinical trials have demonstrated excellent safety and encouraging outcomes. A review of these trials is the focus of this article, in addition to the analysis of ongoing studies, and the possible future applications of this technique.
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Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death and disability in the United States and other developed nations, and is rising rapidly in the rest of the world. Low-density lipoprotein (LDL) is the major atherogenic particle in most patients at high risk for ASCVD events, and statin-based LDL-lowering treatment is the major focus of treatment for prevention of ASCVD. Despite this, an estimated 57 million US adults (25%) still have moderately elevated levels of LDL-cholesterol (LDL-C) > 160 mg/dL, and many others have an LDL-C above the level considered appropriate for their high-risk status. ⋯ These antibodies are at least as effective as statins for LDL-C lowering (or more so), and their effects are additive to those of statins. To date, they have been well tolerated and apparently safe in clinical trials. Long-term randomized, controlled trials of their safety, tolerability, and ability to reduce ASCVD are now underway.