Schaefer - Figure 22 - Conclusions
This final Figure, lists 5 conclusions summarizing where we are now with our understanding of HDL cholesterol particles and therapeutical strategies for influencing their effects on CHD:
- Statins, of course, are the drugs of choice for CHD risk reduction and LDL lowering, but they can modestly affect HDL and rearrange the HDL from smaller to larger particles, in part because they may decrease the activity of CETP.
- Niacin is the most effective agent currently available for raising serum HDL cholesterol levels. It has been shown to have the further benefit that it increases large HDL particles by >100% and up-regulates the macrophage ABCA1 transporter. In current medical practice, the strategy of choice for HDL raising is niacin on top of a statin, but this awaits testing in more large, randomized trials.
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Fibrates are very effective triglyceride lowering agents. They are also interesting drugs in that they don’t increase the numbers of large HDL particles; instead they increase intermediate HDL particles. Gemfibrozil has been clearly shown to have benefit in some studies (although there are risks of combining gemfibrozil with a statin); more recently, fenofibrate has not been shown to have significant benefit on endpoints in diabetic patients.
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Fenofibrates up-regulate lipoprotein lipase, so they are very good triglyceride lowering agents. They may affect apoA-I and apoA-II gene expression, but they also enhance apoA-I fractional clearance, so at the end of the day, you only see a significant increase in HDL.
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CETP inhibitors can definitely raise the mass of very large HDL particles by more than 150%. The question is, are they physiologic, because it is known that they form a complex between the drug, HDL, and CETP, which may not be a good thing. There are a couple of large, randomized clinical trials currently ongoing to assess the benefits of CETP inhibitors, but the one CETP inhibitor that was already tried (torcetrapib) caused excess mortality. However, torcetrapib also raised blood pressure, which the other agents do not do.
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ApoA-I infusion therapy is quite effective in short-term studies and may be useful in the future in acute coronary syndromes, given weekly over 5 weeks. This approach does have a role, but exactly what role that is going to be remains to be determined.
Schaefer E.
J Clin Lipidol.
2011; 5(6).
