Rosuvastatin vs Atorvastatin

Abstract & Commentary

Synopsis: In heterozygous familial hypercholesterolemia patients, rosuvastatin produced significantly greater reductions in LDL cholesterol, increases in HDL cholesterol, beneficial changes in other lipid values, and achievement of NCEP cholesterol goals than observed with equivalent doses of atorvastatin, with a similar adverse event profile.

Source: Stein EA, et al. Am J Cardiol. 2003;92: 1287-1293.

Rosuvastatin is a new statin whose efficacy was compared to that of atorvastatin in 623 patients with heterozygous familial hypercholesterolemia. The study design was 3:1 weight randomized to the new drug, double-blind, parallel group, and forced titration to 80 mg per day. There was a 6-week run-in period of no cholesterol-lowering drugs and the National Cholesterol Education Program (NCEP) step I diet. Then randomization was begun with 20 mg/d of each drug for 6 weeks, then 40 mg/d for 6 weeks, and finally 80 mg/d for 6 weeks. Subsequently, patients were offered an open-label, long-term extension on rosuvastatin 80 mg/d. The primary end point was change in LDL cholesterol at 18 weeks. Mean LDL cholesterol after the 6-week run-in phase was 292 mg/dL in the rosuva group and 288 in the atorva group (P = NS); HDL cholesterol was 48 and 47 and triglycerides were 160 and 159, respectively. Rosuva reduced LDL more than atorva (-58 vs -50%; P < .001) and increased HDL more (12 vs 3%, P < .001). Also, apolipoprotein B was reduced more and apolipoprotein A-1 was increased more by rosuva. Changes in triglycerides were similar with the 2 agents. The percentage of patients achieving NCEP LDL cholesterol goals was higher on rosuva (58 vs 44%; P < .001). Both agents reduced high sensitivity CRP similarly. Both drugs were well tolerated: adverse events resulting in drug discontinuation were 3% and 2%, with myalgia, asthenia, and nausea being most common. Clinically significant increases in alanine aminotransferase (> 3× upper limit of normal on 2 consecutive occasions) were observed in < 1% of patients. No clinically relevant increases in creatine kinase (> 10× upper limit of normal) occurred. Stein and associates concluded that in heterozygous familial hypercholesterolemia patients, rosuvastatin produced significantly greater reductions in LDL cholesterol, increases in HDL cholesterol, beneficial changes in other lipid values, and achievement of NCEP cholesterol goals than observed with equivalent doses of atorvastatin with a similar adverse event profile.

Comment by Michael H. Crawford, MD

For those patients who could not achieve cholesterol-lowering goals with 80 mg/d of atorvastatin, we used to have cervistatin until it was removed from the market due to excessive adverse events. Fortunately, we now have another potent statin alternative that seems to have a low incidence of adverse events. Even in the open-label extension, the incidence of clinically evident myopathy was < 1%. This is good news given the bad experience with cervistatin. What is also remarkable is the robust increase in HDL cholesterol with this drug (12%). Triglyceride values were also reduced but by a similar amount on both drugs.

Whether these impressive changes in the lipid profile will translate to a reduction in clinical events that is greater with rosuvastatin remains to be proven. Interestingly, high-sensitivity CRP was reduced similarly by both agents.

Dr. Crawford is Professor of Medicine, Associate Chief of Cardiology for Clinical Programs, University of California, San Francisco.