Cholesterol-Lowering Combination of Extended-Release Niacin (NIASPAN) Plus Simvastatin (ZOCOR) Misses the Mark

In May, the U.S. National Institutes of Health’s (NIH) National Heart, Lung and Blood Institute prematurely stopped a randomized clinical trial involving high-dose, extended-release niacin (NIASPAN) added to the statin drug simvastatin (ZOCOR) in people with vascular and heart disease. The intent of the trial had been to evaluate whether the combination of high-dose extended-release niacin with simvastatin was more effective than simvastatin alone at reducing the risk of heart attacks and strokes.

The trial was stopped because the combination did not reduce the risk of cardiovascular events, including heart attack and stroke, compared to the risk in people using simvastatin alone. There was also, in the group getting both drugs, a small, unexplained increase in ischemic strokes, which occur when an artery to the brain is blocked.

In 2010, more than 800,000 prescriptions were dispensed for the combination product consisting of extended-release niacin with simvastatin, sold as SIMCOR and approved for sale by the Food and Drug Administration (FDA) in 2008. SIMCOR prescription sales figures for the year 2010 are currently not available. However, in that same year, there were more than 5.6 million prescriptions ordered in U.S. pharmacies for extended-release niacin, at a retail cost approaching $800 million.

The NIH trial was called Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglyceride and Impact of Global Health Outcomes (AIM-HIGH) and began in September 2005. The fact that the combination of extended-release niacin and simvastatin did not improve outcomes compared to simvastatin alone means that this combination and, as a consequence, AIM-HIGH missed the high mark the study had set.

AIM-HIGH study of HDL and LDL cholesterol levels

The theory behind the AIM-HIGH trial was that increasing HDL (“good”) cholesterol levels — as can occur with extended-release niacin — would lower heart attacks, strokes and other adverse events in patients with a history of cardiovascular disease and controlled (with simvastatin) LDL (“bad”) cholesterol levels. AIM-HIGH included 3,414 American and Canadian participants who had a history of cardiovascular disease and were taking a statin drug to keep their LDL cholesterol low. All trial subjects were started on a standard therapy of 40 milligrams (mg) of simvastatin per day (which could be increased if the target LDL level was not reached). Participants were then randomly assigned (approximately 1,700 to a group) to receive either 1,500 to 2,000 mg per day of extended-release niacin or a placebo.

One purpose of the AIM-HIGH study was to provide definitive data from a randomized clinical trial versus information from observational studies. A large number of observational studies have consistently shown that low HDL cholesterol increased the risk of cardiovascular events, independent of high LDL cholesterol. Studies have shown that this same effect is seen with low HDL cholesterol and high triglycerides, another type of blood fat, despite intensive management of LDL cholesterol.

To be eligible for the study, the AIM-HIGH subjects had to have low levels of HDL cholesterol (defined as equal to or less than 40 mg per deciliter [dL]) and high levels of triglycerides (defined as equal to or greater than 150 mg per dL), implying that they were at significant risk of experiencing future adverse cardiovascular events. Niacin, also known as vitamin B3, has long been known to raise HDL levels and lower triglyceride levels.

There were 28 (1.6 percent) ischemic strokes (one of three types of stroke) in the group taking simvastatin plus extended-release niacin compared to 12 (0.7 percent) in participants receiving simvastatin with a placebo, a result complicated by some of the stroke patients ceasing to take their extended-release niacin before the study was concluded. However, the study clearly shows that the combination of these two drugs did not reduce the risk of heart attacks and stroke.

Special warnings about niacin and extended-release niacin

Some consumers may be tempted to reduce the cost of cholesterol-lowering treatment by purchasing niacin from health food stores or other outlets. All forms of niacin are not the same as prescription extended-release niacin. This drug should not be substituted for equivalent doses of immediate-release (crystalline) niacin. Do not switch between forms of niacin without first talking to your doctor, because severe liver damage can occur. There are also other adverse effects with immediate-release niacin compared to those adverse events associated with the extended-release form.

What You Can Do

You should not discontinue the use of any cholesterol-altering medication without first consulting the prescribing doctor.

If you have been prescribed extended-release niacin in addition to simvastatin or the combination drug SIMCOR, which contains both extended-release niacin and simvastatin, you should consult your doctor about the lack of benefits and possible adverse effects of this combination of drugs.

You should make an honest effort to control your cholesterol levels through a healthy diet and exercise.

Consumers may report serious adverse events or product quality problems to the FDA’s MedWatch Adverse Event Reporting program online or by regular mail, fax or phone.

• Online: www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm
• Regular mail: Use postage-paid, pre-addressed FDA form 3500 and mail to MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787
• Fax: (800) FDA-0178
• Phone: (800) FDA-1088