NIH stops clinical trial on combination cholesterol treatment

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The National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health has stopped a clinical trial studying a blood lipid treatment 18 months earlier than planned. The trial found that adding high dose, extended–release niacin to statin treatment in people with heart and vascular disease, did not reduce the risk of cardiovascular events, including heart attacks and stroke.

Participants were selected for AIM–HIGH because they were at risk for cardiovascular events despite well–controlled low–density lipoprotein (LDL or bad cholesterol). Their increased risk was due to a history of cardiovascular disease and a combination of low high–density lipoprotein (HDL or good cholesterol) and high triglycerides, another form of fat in the blood. Low HDL and elevated triglycerides are associated with an increased risk of cardiovascular events. While lowering LDL decreases the risk of cardiovascular events, it has not been shown that raising HDL similarly reduces the risk of cardiovascular events. During the study’s 32 months of follow–up, participants who took high dose, extended–release niacin and statin treatment had increased HDL cholesterol and lowered triglyceride levels compared to participants who took a statin alone. However, the combination treatment did not reduce fatal or non–fatal heart attacks, strokes, hospitalizations for acute coronary syndrome, or revascularization procedures to improve blood flow in the arteries of the heart and brain.

The AIM–HIGH trial, which stands for Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health, enrolled 3,414 participants in the United States and Canada with a history of cardiovascular disease who were taking a statin drug to keep their LDL cholesterol low. Study participants also had low HDL cholesterol and high triglycerides, which meant that they were at significant risk of experiencing future cardiovascular events. Niacin, also known as Vitamin B3, has long been known to raise HDL and lower triglycerides. Eligible participants were randomly assigned to either high dose, extended–release niacin (Niaspan) in gradually increasing doses up to 2,000 mg per day (1,718 people) or a placebo treatment (1,696 people). All participants were prescribed simvastatin (Zocor), and 515 participants were given a second LDL cholesterol–lowering drug, ezetimibe (Zetia), in order to maintain LDL cholesterol levels at the target range between 40–80 mg/dL.
Researchers began recruiting participants in early 2006. The study was scheduled to finish in 2012. The average age of the participants was 64 years. Pre-existing medical conditions included coronary artery disease (92 percent); metabolic syndrome, which is a cluster of risk factors for heart disease (81 percent); high blood pressure (71 percent); and diabetes (34 percent). More than half of participants reported having a heart attack prior to entering the study.

The rationale for the AIM–HIGH study was based in part on a large number of observational studies that consistently showed that low HDL cholesterol increases the risk of cardiovascular events in men and women, independent of high LDL cholesterol. In addition, previous small clinical studies showed that relatively high residual cardiovascular risk exists among patients with cardiovascular disease, low HDL cholesterol, and high triglycerides despite intensive management of LDL cholesterol.