Robinson - Figure 11 - Evidence for non-statin Rx Text

All of the evidence for CVD prevention with non-statin therapies comes from severely high cholesterolemic populations, not necessarily FH patients, for the reasons discussed above. As usual, these populations were predominantly male, but they still serve as a general guide to non-statin therapies:

• There have been several studies of diet, primarily emphasizing polyunsaturated fatty acids (PUFAs), that have shown a modest reduction in CHD consistent with a modest lowering of LDL.
• There have been several studies with bile acid sequestrants, both cholestyramine and colestipol, that have shown a reduction in CHD events, again commensurate with the degree of LDL lowering, which is more modest than that observed with statins. Colesevelam is also a bile acid sequestrant; it does not have any outcomes data, although it has the same mechanism of action as the older bile acid sequestrants but with a much better adverse effect profile and fewer drug-drug interactions.
• Nicotinic acid, or niacin, titrated up to 2 g/day, was shown in the Coronary Drug Project[13] to reduce nonfatal coronary events and on the basis of these well-known results as well as others, niacin is certainly a non-statin therapy option. Niacin also raises HDL cholesterol and has some lowering effect on triglycerides, so it is not always clear which effect is providing the benefit with niacin. Two important drawbacks with this agent are a difficult side effect profile that often severely limits patient adherence, and this is exacerbated because it is necessary to slowly up-titrate the niacin does to at least 1.5 – 2 g/day to get a noticeable LDL lowering effect.
• Ileal bypass surgery has also been determined to reduce coronary events in a clinical trial.[14] Surgery is always a drastic approach and obviously it cannot be routinely recommended, but it might be an option for those who cannot tolerate statins or still have very high levels of LDL despite maximal therapy
• Finally gemfibrozil is another drug that has been shown to reduce CHD events in both hypercholesterolemic, high triglyceride populations as well as low LDL, hypertriglyceridemic populations – but again, the committee has not recommended gemfibrozil for coronary prevention because of significant safety concerns when this drug is used in combination with statins. In addition, gemfibrozil has only very modest effects on LDL cholesterol levels.

Robinson J. J Clin Lipidol. 2011; 5(6).