Atorvastatin (Lipitor) is a hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor or “statin.” HMG-CoA reductase is the enzyme responsible for converting HMG-CoA to mevalonate; this occurs at an early and rate-limiting step in the biosynthesis of cholesterol (see figure).
Although a number of “statins” are now available, atorvastatin is the only drug in this class indicated as an adjunct to diet in the reduction of elevated total cholesterol, low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (apo-B), and triglyceride (TG) levels in patients with primary hypercholesterolemia and mixed dyslipidemia. It is the first drug of its class specifically indicated for lowering both low-density lipoprotein cholesterol and triglyceride levels. It is also the only statin indicated for the reduction of total cholesterol and low-density lipoprotein cholesterol in patients with homozygous familial hypercholesterolemia, a rare, serious, life-threatening, autosomal dominant, inherited disorder of lipid metabolism.
In head-to-head clinical trials when starting doses were compared, atorvastatin was superior to lovastatin, pravastatin, and simvastatin in reducing elevated total cholesterol, low-density lipoprotein cholesterol, and triglycerides. In two placebo-controlled, dose-response studies in hypercholesterolemic patients, once-daily administration of atorvastatin significantly reduced low-density lipoprotein cholesterol by 39% to 60% across the dose range of 10 mg to 80 mg. In addition, atorvastatin reduced triglyceride levels by 19% to 37% across the dose range. In a large clinical study, the number of patients meeting the National Cholesterol Education Program – Adult Treatment Panel II target levels, while taking daily 10-mg doses of Lipitor, was assessed. After 16 weeks, 93% of patients with fewer than two risk factors for coronary heart disease and a baseline low-density lipoprotein cholesterol of 190 mg/dL or lower reached a target of 160 mg/dL or lower, and 19% of those with coronary heart disease and an low-density lipoprotein cholesterol of 130 mg/dL or more reached a target of 100 mg/dL low-density lipoprotein cholesterol or lower.
The most frequent treatment-related adverse events are constipation, flatulence, dyspepsia, and abdominal pain. Fewer than 2% of patients treated with Lipitor in controlled studies discontinued treatment because of drug-related adverse events. Elevations of serum transaminases occurred in fewer than 1% of patients, but it is recommended that liver function tests be performed before the start of treatment, after 6 and 12 weeks, and periodically thereafter. As with other statins, the risk of myopathy is increased when the drug is taken with cyclosporine, fibric acid derivatives, niacin, erythromycin, or azole antifungals. Patients should be advised to report unexplained muscle pain, tenderness, or weakness, especially if accompanied by malaise or fever.