Hyperlipidemias combination therapy

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. 

The combination of amprenavir and low-dose ritonavir has been associated with elevations of cholesterol and triglycerides, AST, and ALT in some patients. Consider appropriate laboratory testing prior to initiating combination therapy with amprenavir and ritonavir and at periodic intervals, or if any clinical signs or symptoms of hyperlipidemia or elevated liver function tests occur during therapy. 

Spence JD, Huff MW, Heidenheim P, Viswanatha A, Munoz C, Lindsay R, Wolfe B, Mills D. Combination therapy with colestipol and psyllium mucilloid in patients with hyperlipidemia. Ann Intern Med 1995 123(7) 493—9. 

Knoll RW, Ciafone R, Galen M. Rhabdomyolysis and renal failure secondary to combination therapy of hyperlipidemia with lovastatin and gemfibrozil. Corm Med (1993) 593-4. 

Dietary measures are initiated first—unless the patient has evident coronary or peripheral vascular disease—and may obviate the need for drugs. Patients with familial hypercholesterolemia or familial combined hyperlipidemia always require drug therapy. Cholesterol and saturated and trans-fats are the principal factors that increase LDL, whereas total fat, alcohol, and excess calories increase triglycerides. 

Combined drug therapy is useful (1) when VLDL levels are significantly increased during treatment of hypercholesterolemia with a resin (2) when LDL and VLDL levels are both elevated initially (3) when LDL or VLDL levels are not normalized with a single agent, or (4) when an elevated level of Lp(a) or an HDL deficiency coexists with other hyperlipidemias. 

Soon after the introduction of highly active antiretroviral combination treatments (HAART), lipodystrophy was associated with the use of protease inhibitors, and several reports have confirmed that a syndrome of peripheral lipodystrophy, central adiposity, breast hypertrophy in women, hyperlipidemia, and insulin resistance with hyperglycemia is an adverse event associated with the use of potent combination antiretroviral therapy, particularly including HIV-1 protease inhibitors (982-987). 

Hyperlipidemia can lead to atherosclerosis and subsequent cardiovascular incidents such as thrombosis and infarction. This condition is often treated by a combination of drug therapy and diet and life-style modifications. Pharmacologic interventions are typically targeted toward decreasing the synthesis of harmful (atherogenic) plasma components, including certain lipoproteins (IDL, LDL, VLDL) that are associated with atherosclerotic plaque formation. 

Renal failure is a relative contraindication to the use of fibric acid agents, as is hepatic dysfunction. Combined statin-fibrate therapy should be avoided in patients with compromised renal function. Gemfibrozil should be used with caution and at a reduced dosage to treat the hyperlipidemia of renal failure. Fibrates should not be used by children or pregnant women. 

A multicenter randomized comparative trial of tacrolimus in combination with azathioprine or mycofenolate mofetU (MMF) versus cyclosporin (microemulsion) with MMF after cadaveric kidney transplantation demonstrated that all regimens yielded similar acute rejection and graft survival rates at 1 year. The tacrolimus-MMF regimen was associated with the lowest rate of steroid-resistant rejection requiring antilymphocyte therapy. In addition, the tacrolimus-treated patients had lower incidence of hyperlipidemia, a side effect of particular concern in these patients [60]. 

Nicotinic acid is approved for the treatment of hyper-cholesterolemia, hypertriglyceridemia, and familial combined hyperlipidemia (Fredrickson s type lla, Mb, IV, and V) (Table 30.2) in patients who have not responded to diet, exercise, and other nonpharmacological methods. It also is approved for nutritional supplementation, the prevention of pellagra, and as adjunct therapy for peripheral vascular disease and circulatory disorders. It is contraindicated in patients with hepatic disease and peptic ulcer disease. Additionally, because of its ability to elevate glucose and uric acid levels, especially when taken in large doses, nicotinic acid should be used with caution in patients who have or are predisposed to diabetes mellitus and gout (15,20,21). 

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