LOVASTATIN 5-YEAR SAFETY AND EFFICACY STUDY

Background: Inhibitors of hydroxymethylglutaryl coenzyme A reductase a re widely used to treat hypercholesterolemia. They have a good short- to medium-term safety profile, but long-term safety data are limited. Methods: Seven hundred forty-five patients with severe hypercholestero lemia (mean baseline plasma cholesterol level on diet, 9.3 mmol/L [360 mg/dL]) were treated with lovastatin for a median duration of 5.2 yea rs. Their mean age at baseline was 50 years, 68% were male, 60% had fa milial hypercholesterolemia, and 42% had a history of coronary heart d isease. Seventy-seven percent of patients had titrations of lovastatin to 80 mg/d, and 58% took other lipid-lowering agents, usually bile ac id sequestrants, concomitantly. Results: The mean changes at 5 years i n total, low-density lipoprotein, and high-density lipoprotein cholest erol were -35%, -44%, and +14%, respectively. Eighty percent of patien ts completed the study, 13% were unavailable for follow-up, 4% were di scontinued due to adverse events unlikely to be related to lovastatin, and 3% (21) were discontinued because of drug-attributable adverse ev ents: marked but asymptomatic increase in aminotransferase values (10 patients), gastrointestinal disturbance (three patients), rash (two pa tients), myalgia (one patient), myopathy (two patients), arthralgia (o ne patient), insomnia (one patient), and weight gain (one patient). Si xteen patients died during the study, all of coronary disease. Of thes e, 14 had coronary heart disease at baseline. There were no deaths att ributable to trauma, suicide, or homicide, and there were only 14 case s of cancer (vs 21 expected). There was no evidence for an adverse eff ect on the lens. Conclusions: Lovastatin is a generally well-tolerated and effective drug during long-term use.