Dyslipidemias, treatment

Malik S, Kashyap ML. Dyslipidemia treatment current considerations and unmet needs. Expert Rev Cardiovasc Ther. 2003 1 121-134. 

Aggressive treatment of diabetic dyslipidemia through diet, weight control, and drugs is critical in reducing risk. Diabetics without diagnosed CHD have the same level of risk as nondiabetics with estabhshed CHD. Thus, the dyslipidemia treatment guidelines for diabetic patients are the same as for patients with CHD, irrespective of whether the diabetic patient has had a CHD event. The first line of treatment for diabetic dyslipidemia usually should be a statin. 

Although no PPARS-specific ligands are currently FDA-approved, GW501516 is a compound being developed jointly by GlaxoSmithKline and Ligand Pharmaceuticals. This compound is currently in Phase II trials for the treatment of dyslipidemia. 

A major component of any IHD treatment plan is control of modifiable risk factors, including dyslipidemia, hypertension, and diabetes. Treatment strategies for dyslipidemia and hypertension in the patient with IHD are summarized in the following paragraphs. Visit chapters in this textbook on the management of hypertension and dyslipidemia for further information. 

Because lipoprotein metabolism and the pathophysiology of atherosclerosis are closely linked, treatment of dyslipidemias is critical for both primary and secondary prevention of IHD-related cardiac events. In 2001, the Adult Treatment Panel III of the National Cholesterol Education Program... 

Like dyslipidemia, hypertension is a major, modifiable risk factor for the development of IHD and related complications. Unfortunately, awareness, treatment, and control of blood pressure are not nearly enough.30 Aggressive identification and control of hypertension is warranted in patients with IHD to minimize the risk of major adverse cardiac events. Goal blood pressure in patients with IHD is less than 140/90 mm Hg or less than 130/80 mm Hg in patients with diabetes. Because of their cardioprotective benefits, 3-blockers and ACE inhibitors (or ARBs in ACE-inhibitor-intolerant patients), either alone or in combination, are appropriate for most patients with both hypertension and IHD. 

The NKF suggests that CKD should be classified as a coronary heart disease (CHD) risk equivalent and the goal LDL-C level should be below 100 mg/dL in all patients with CKD.22 The most frequently used agents for the treatment of dyslipidemias in patients with CKD are the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors ( statins ) and the fibric acid derivatives. However, other treatments have been studied in patients with CKD and should be considered if first-line therapies are contraindicated. 

Insulin resistance has been associated with a number of other cardiovascular risks, including abdominal obesity, hypertension, dyslipidemia, hypercoagulation, and hyperinsulinemia. The clustering of these risk factors has been termed metabolic syndrome. It is estimated that 50% of the United States population older than 60 years of age have metabolic syndrome. The most widely used criteria to define metabolic syndrome were established by the National Cholesterol Education Program Adult Treatment Panel III Guidelines (summarized in Table 40-2). 

For all ACS patients, treatment and control of modifiable risk factors such as hypertension, dyslipidemia, and diabetes mellitus are essential. 

The principal use of niacin is for mixed hyperlipidemia or as a second-line agent in combination therapy for hypercholesterolemia. It is a first-line agent or alternative for the treatment of hypertriglyceridemia and diabetic dyslipidemia. 

Near-normal glycemia reduces the risk of microvascular disease complications, but aggressive management of traditional cardiovascular risk factors (i.e., smoking cessation, treatment of dyslipidemia, intensive blood pressure control, antiplatelet therapy) is needed to reduce macrovascular disease risk. 

Claudication and nonhealing foot ulcers are common in type 2 DM. Smoking cessation, correction of dyslipidemia, and antiplatelet therapy are important treatment strategies. 

Multiple-risk-factor intervention (treatment of dyslipidemia and hypertension, smoking cessation, antiplatelet therapy) reduces macrovascular events. 

The targeting of the lipid absorption and metabolism pathways has yielded several promising venues for the treatment of dyslipidemia and insulin resistance. Small molecule inhibitors of MTP have conferred significant reductions in total and LDL cholesterol, as well as plasma TG, in human subjects. While some mechanism-related side effects due to increased hepatic and intraintestinal TG... 

The clinical validation of new approaches to raise functional HDL will potentially lead to a paradigm shift in the treatment of atherosclerosis, dyslipidemia and metabolic syndrome. 

Sankyo/Kowa, 2003), an analog of mevastatin-like rosuvastatin, has been approved for the treatment of dyslipidemia in Japan/ ... 

Primary hypercholesterolemia/mixed dyslipidemia For the treatment of primary hypercholesterolemia (heterozygous familial and nonfamilial) and mixed dyslipidemia (Frederickson Types lla and Mb) in the following Patients treated with lovastatin who require further TG-lowering or FIDL-raising who may benefit from having niacin added to their regimen patients treated with niacin who require further... 

Simvastatin is also used in combination with nicotinic acid. It is found to be the most useful drug combination for the treatment of dyslipidemias associated with coronary artery disease. It is particularly effective in normalizing the lipid profiles of patients with familial combined dyslipidemia. 

All NRTIs may be associated with mitochondrial toxicity, probably owing to inhibition of mitochondrial DNA polymerase gamma. Less commonly, lactic acidosis with hepatic steatosis may occur, which can be fatal. NRTI treatment should be suspended in the setting of rapidly rising aminotransferase levels, progressive hepatomegaly, or metabolic acidosis of unknown cause. The thymidine analogues zidovudine and stavudine may be particularly associated with dyslipidemia and insulin resistance. Also,... 

Indication Adjunct to diet for the reduction of elevated total cholesterol. LDL. apo B. and TG levels in patients with primary hypercholesterolemia (heterozygous familial and nonfamilial). mixed dyslipidemia (Fredrickson types Ila and 1 lb), elevated TG (type IV) and primary dysbetali-poproteinemia (type III) Adjunct to other lipid lowering treatments for homozygous familial hypercholesterolemia ... 

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