Lipid-Lowering Drugs and Clinical Outcomes

One of the articles in the next (June 24, 2013) issue of The Medical Letter will be on the combination, called Liptruzet, of atorvastatin and the cholesterol absorption inhibitor ezetimibe for treatment of hyperlipidemia. It is the second combination of ezetimibe and a statin to be marketed in the US; Vytorin, which combines ezetimibe with simvastatin has been around since 2004.

The statins make up the only category of lipid-lowering drugs in which all are accepted as improving clinical outcomes (lowering the incidence of cardiovascular events) as well as just lowering serum cholesterol levels. It was not always so. We have reviewed them all over the years, and I remember very well cautioning our readers against prescribing atorvastatin just because FDA-approved doses of the drugs lowered cholesterol levels more than any other statin; improvement in clinical outcomes, we reminded them,  remained to be demonstrated. Then they were demonstrated for atorvastatin, and Lipitor quickly became a best seller. When rosuvastatin (Crestor) came along, the same sequence was repeated.

For the second-line drugs that are added to a statin when patients on monotherapy do not reach their LDL-C targets, the stories have been more mixed.  Among the fibrates, for instance, gemfibrozil (Lopid) significantly lowered coronary mortality in the Helsinki Heart Study, but it also inhibited the metabolism of all the most popular statins, increasing the risk of rhabdomyolysis and becoming a virtual pariah. Clinical trials with other fibrates added to a statin did not show a significant improvement in cardiovascular outcomes.

Niacin is probably the most maddening of the second-line lipid-lowering drugs. It not only lowers LDL-C, but also sharply increases HDL-C, decreases triglycerides, and changes small, dense LDL particles to large, buoyant, less dangerous forms. Surely all that should have a favorable impact on cardiovascular disease. Well, yes and no. Some studies have found that it did, but others found no effect on outcomes, and the consensus verdict seems to be unproven.

Ezetimibe prevents absorption of cholesterol from the GI tract. It does what all that dietary advice we get from all sides wants us to achieve. Surely, surely, it must…. But no, it does not, at least not yet. Up until now, no published data are available showing that ezetimibe alone or added to a statin improves clinical outcomes. The newest combo adds ezetimibe to the statin with probably the best-documented track record in lowering the incidence of cardiovascular disease. Perhaps that will do the trick. Watch your newsstand for the June 24th issue of The Medical Letter. Or, if you can’t wait that long, check out our web site on June 20th.

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  1. Herb Kleinman says:

    As I mentioned in my comments sent through the editorial comment section of the main website, I think even the lukewarm recommendation oversells this product. A serious review of the data brings into question the validity of the “LDL hypothesis”. This combo was pushed out as the drug companies are desperate due to the lack of blockbusters in the pipeline and previous big sellers now having generic competition.

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