Monday, August 4, 2014

Effects of Extended-Release Niacin with Laropiprant in High-Risk Patients

BACKROUND – Patients with evidence of vascular disease are at increased risk for subsequent vascular events despite effective use of statins to lower the low-density lipoprotein (LDL) cholesterol level. Niacin lowers the LDL cholesterol and raises the high-density lipoprotein (HDL) cholesterol level, but its clinical efficacy and safety are uncertain.

METHODS – After a prerandomization run-in phase to standardize the background statin-based LDL cholesterol-lowering therapy and to establish participants’ ability to take extended-release niacin without clinically significant adverse effects, we randomly assigned 25,673 adults with vascular disease to receive 2 g of extended-release niacin and 40 mg of laropiprant or a matching placebo daily. The primary outcome was the first major vascular event (nonfatal myocardial infarction, death from coronary causes, stroke, or arterial revascularization).

RESULTS – During a median follow-up period of 3.9 years, participants who were assigned to extended-release niacin-laropiprant had an LDL cholesterol level that was an average of 10 mg per deciliter lower and an HDL cholesterol level that was an average of 6 mg per deciliter higher than the levels in those assigned to placebo. Assignment to the niacin-laropiprant, as compared with assignment to the placebo, had no significant effect on the incidence of major vascular events. Niacin-laropiprant was associated with an increased incidence of disturbances in diabetes control that were considered to be serious, as well as increases in serious adverse events associated with the gastrointestinal system, skin, and unexpectedly, infection and bleeding.

CONCLUSIONS – Among participants with atherosclerotic vascular disease, the addition of extended-release niacin-laropiprant to statin-based LDL cholesterol-lowering therapy did not significantly reduce the risk of major vascular events but did increase the risk of serious adverse events.

Please reread the first sentence – Patients with vascular disease are at increased risk of for subsequent vascular events despite the use of statins. The slight benefit from statins comes from reducing inflammation, not from lowering LDL cholesterol.

What this summary doesn’t disclose is that Merck also added another drug to the niacin-statin combination to prevent flushing. Niacin, even in small doses can cause a flushing of the skin accompanied by itching. In previous studies about 25% of participants discontinued niacin therapy due to these side effects. The researchers admit that they don’t know if the negative side effects were related to the niacin or the third drug.

Clinically, I use the niacin without the statins and it works great. I use a much lower dose, up to 500 mg rather than the 2 g used in the study. Yes, my patients “flush” but I have long believed that the flush is important to the biochemical metabolism of niacin. Recent research indicates that the flush comes from the epithelial cells of the body using cholesterol in the formation of prostaglandin inflammation. This chemical process would lower LDL and raise HDL levels through normal biochemical pathways in the body.

Any nutrient – vitamin, mineral, phytochemical – can act like a drug if the dosage is too high. This is a constant concern in daily practice. Nutrients facilitate biochemistry while drugs mandate. I’ll admit that I occasionally cross that line. When I do, it is for short term therapy and I monitor my patient closely.
Drug-nutrient interactions are common place. I have textbooks and internet web sites dedicated to this subject. I am not surprised at the results of this study. I think the study should have been reversed – test niacin and a placebo against niacin and a statin in a double blind study.

Finally, the premise is all wrong. Manipulating the LDL and HDL levels with drugs, vitamins, or even combinations of drugs and vitamins is not the answer. When a patient has high cholesterol, you need to ask why it is high rather than just force it down. Is it diet and lifestyle? Do they have hypothyroidism? Do they suffer from dysbiosis? Commonly, the answer is more than one of these issues is at fault. Correct the metabolism and the serum lipids will come into balance. High cholesterol is a test result, not a disease.

If you want to reduce cholesterol levels, lower LDL and raise HDL, niacin can be an excellent tool. Work with a nutritionist who will view your serum lipids as a reflection of the health of the body rather than a disease process.

Source: New England Journal of Medicine -July 17, 2014