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Q: What are the advantages and disadvantages of adding a fibrate or niacin?
A: The addition of a fibrate should raise the HDL-C into the desirable range. However, the risk of rhabdomyolysis is increased in this situation. A joint statement issued by the American College of Cardiology, the American Heart Association, and the National Heart, Lung and Blood Institute (ACC/AHA/NHLBI)11 states that statin treatment alone or fibrate treatment alone is associated with a small risk of severe myopathy (approximately 0.8% to 0.9%), and that the risk is increased when a statin and a fibrate are used in combination. Although no head-to-head studies have compared the incidence of myopathy/rhabdomyolysis in patients treated with pravastatin and other statins in combination with fibrates, pravastatin offers some differences among other marketed statins because it does not enter the myocyte. In addition, it has a clear route of exertion by the liver and thus may have a better safety profile with regard to rhabdomyolysis compared to other statins.12 In addition, fenofibrate may have a lowered risk of rhabdomyolysis than gemfibrozil and would be the fibrate of choice in this situation.13
Nicotinic acid has a powerful effect on elevating both total HDL and the HDL2. Unfortunately, the side effects of nicotinic acid (flushing, itching) make crystalline nicotinic acid acceptable to only a minority of patients. Slow-release over-the-counter nicotinic acid has been associated with hepatitis and liver failure. The acid has a minimal effect on the lipid profile, and its high risk-to-benefit ratio makes it unacceptable. Extended-release nicotinic acid (Niaspan®) has a similar advantage of lowering LDL and triglycerides, as well as elevation of HDL and HDL2 as the crystalline form with fewer side effects.
Nicotinic acid may increase insulin resistance and worsen glycemic control. This generally does not occur when doses of up to 1 gram per day are utilized; however, patients should be monitored closely during treatment for glucose elevations. The ADMIT investigators14 noted only transient increases in average plasma glucose values in patients with diabetes treated with niacin (crystalline nicotinic acid) doses of up to 3 g/d. A1c levels were unchanged from baseline to follow-up (up to 60 weeks), while HDL-C increased by 29% (p<0.001), LDL- C decreased by 8%, and triglycerides decreased by 23%.
The combination of niacin and a statin is judged to carry a lower risk for myopathy than does the combination of a statin plus fibrate; however, patients should be monitored for this adverse event (Table 4).11
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