Scope and Limitations of Marketed Therapies

Statins [3,16] 20-60 20 0 2-10 Muscle toxicity, liver enzyme elevation 

Niacin ER [17,18] 10-22 11 0 10-30 Skin flushing, gastrointestinal, hepatic toxicity 

Niacin ER/ lovastatin [19] 25 5 16-42 30-41 Flushing, pruritis, gastro-intestinal symptoms 

Colesevelam [22,23] 14-28 2-3 Caution in patients with fat-soluble vitamin deficiency 

As indicated in Table 1, statins, which block cholesterol biosynthesis by inhibition of hepatic HMGCoA reductase, have been used extensively to reduce LDL-C levels. At most therapeutic doses, statins marginally increase HDL levels by 5-10% [3,16]. The HDL elevation observed with statins has been highly variable and not easily extrapolated from the effects on LDL. A recent study (STELLAR) demonstrated increased HDL elevation with the use of rosuvastatin compared to simvastatin, pravastatin or atorvastatin (10% vs. 2-6%) [16,24], Although the mechanism of HDL elevation by statins is not clearly understood, it is proposed that statins enhance hepatic apoA-I synthesis [25] and decrease apoB-containing lipoproteins [26]. A number of clinical trials have demonstrated that statins reduce the risk of major coronary events. However, it is not clear if the statin-induced rise in HDL levels is an independent contributor to the reduced risk of coronary events. The observed small increase in HDL and adverse side effect profile related to liver function abnormalities and muscle toxicity limits the use of statins as monotherapy for HDL elevation [27], 

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