Safety and tolerability of simvastatin plus niacin in patients with coronary artery disease and low high-density lipoprotein cholesterol (The HDL Atherosclerosis Treatment Study)

• Published in: The American journal of cardiology Vol. 93; no. 3; pp. 307 - 312
• Main Authors: Zhao, Xue-Qiao, Morse, Josh S, Dowdy, Alice A, Heise, Nancy, DeAngelis, Debbie, Frohlich, Jiri, Chait, Alan, Albers, John J, Brown, B.Greg
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-02-2004; Elsevier; Elsevier Limited
• Subjects: Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Blood Glucose - drug effects; Cardiology; Cardiology. Vascular system; Cardiovascular disease; Cholesterol, HDL - blood; Coronary Artery Disease - blood; Coronary heart disease; Double-Blind Method; Drug therapy; Drug Therapy, Combination; Female; Heart; Humans; Hypolipidemic Agents - adverse effects; Insulin - blood; Lipids; Liver - drug effects; Male; Medical sciences; Middle Aged; Muscle, Skeletal - drug effects; Niacin - adverse effects; Simvastatin - adverse effects; High; Human; Toxicity; Simvastatin; Nicotinic acid; Cardiovascular disease; Coronary heart disease; Vascular disease; Lipoprotein LDL; Treatment; Cholesterol HDL; Atherosclerosis; Safety
• ISSN: 0002-9149; 1879-1913
• DOI: 10.1016/j.amjcard.2003.10.009

The high-density lipoprotein (HDL)-Atherosclerosis Treatment Study showed that simvastatin plus niacin (mean daily dose 13 mg and 2.4 g, respectively) halt angiographic atherosclerosis progression and reduce major clinical events by 60% in patients with coronary artery disease (CAD) who have low HDL, in comparison with placebos, over 3 years. How safe and well-tolerated is this combination? One hundred sixty patients with CAD, including 25 with diabetes mellitus, with mean low-density lipoprotein cholesterol of 128 mg/dl, HDL cholesterol of ≤35 mg/dl (mean 31), and mean triglycerides of 217 mg/dl were randomized to 4 factorial combinations of antioxidant vitamins or their placebos and simvastatin plus niacin or their placebos. Patients were examined monthly or bimonthly for 38 months; side effects (gastrointestinal upset, nausea, anorexia, vision, skin, and energy problems, or muscle aches) were directly queried and recorded. Aspartate aminotransferase, creatine phosphokinase (CPK), uric acid, homocysteine, and fasting glucose levels were regularly monitored. A safety monitor reviewed all side effects and adjusted drug dosages accordingly. Patients who received simvastatin plus niacin and those on placebo had similar frequencies of clinical or laboratory side effects: any degree of flushing (30% vs 23%, p = NS), symptoms of fatigue, nausea, and/or muscle aches (9% vs 5%, p = NS), aspartate aminotransferase (SGOT) ≥3 times upper limit of normal (3% vs 1%, p = NS), CPK ≥2 times upper limit of normal (3% vs 4%, p = NS), CPK ≥5 times upper limit of normal, new onset of uric acid ≥7.5 mg/dl (18% vs 15%, p = NS), and homocysteine ≥15 μmol/L (9% vs 4%, p = NS). Glycemic control among diabetics declined mildly in the simvastatin-niacin group but returned to pretreatment levels at 8 months and remained stable for rest of the study. This combination regimen was repeatedly described by 91% of treated patients and 86% of placebo subjects as “very easy” or “fairly easy” to take. Thus, the simvastatin plus niacin regimen is effective, safe, and well tolerated in patients with or without diabetes mellitus.