AIM-HIGH trial goes down

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The National Heart, Lung and Blood Institute (NHLBI), a division of the National Institutes of Health, has stopped a clinical trial, co-sponsored by Abbott Laboratories, which was 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 LDL cholesterol. Their increased risk was due to a history of cardiovascular disease and a combination of low HDL cholesterol and high triglycerides.

During the study’s 32 months of follow-up, participants who took high dose, extended-release niacin and a statin had increased HDL cholesterol and lowered triglyceride levels compared with participants who took a statin alone. However, the NHLBI said that the combination treatment did not reduce fatal or non-fatal heart attacks, strokes, hospitalizations for acute coronary syndrome or revascularization procedures.

“Seeking new and improved ways to manage cholesterol levels is vital in the battle against cardiovascular disease,” said Susan B. Shurin, MD, acting director of the NHLBI. “This study sought to confirm earlier and smaller studies. Although we did not see the expected clinical benefit, we have answered an important scientific question about treatment for cardiovascular disease.”

AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health) enrolled 3,414 participants in the U.S. 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. Niacin, also known as Vitamin B3, has long been known to raise HDL and lower triglycerides, according to the NHLBI. Eligible participants were randomly assigned to either high dose, extended-release niacin (Niaspan, Abbott) 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, Merck Pharmaceuticals), and 515 participants were given a second LDL cholesterol-lowering drug, ezetimibe (Zetia, Merck) to maintain LDL cholesterol levels at the target range between 40-80 mg/dL.

The NHLBI funded the AIM-HIGH study with additional support from Abbott, based in Abbott Park, Ill.

In a statement, Abbot said, “The AIM-HIGH study population does not represent all patient populations in whom the importance of treating low HDL and lowering triglycerides with Niaspan may be significant. Abbott will reflect the relevant study findings in the label after finalization of the AIM-HIGH study results and appropriate review.”

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.

However, efforts to find HDL-raising treatments that actually reduce this residual risk have thus far proved disappointing, the NHBLI reported. Fenofibrate, an HDL-raising drug, failed to reduce the rate of cardiovascular events in patients with diabetes in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial despite favorable effects on HDL and triglycerides.  Another HDL-raising drug, torcetrapib, actually increased the rate of cardiovascular events in the ILLUMINATE (Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events) trial despite lowering LDL and triglycerides and raising HDL levels,