A multinational clinical trial program, published in the journal "Cardiology" shows that rosuvastatin is well tolerated by a broad range of patients with dyslipidemia, and its safety profile is similar to those of comparator statins investigated in this clinical program.
Following the resurgence of interest in statin safety, this report is an updated comprehensive summary of data from more than 16,800 patients.
The safety and tolerability of rosuvastatin were assessed using data from 16,876 patients who received rosuvastatin 5-40 mg in a multinational phase II/III/IIIb/IV program, representing 25,670 patient-years of continuous exposure to rosuvastatin. An integrated database, consisting of 33 trials whose databases were locked up to and including September 16, 2005, was used to examine adverse events and laboratory data.
In placebo-controlled trials, adverse events irrespective of causality assessment occurred in 52.1% of patients receiving rosuvastatin 5-40 mg (n = 931) and 51.8% of patients receiving placebo (n = 483). In all controlled clinical trials with comparator statins, rosuvastatin 5-40 mg was associated with an adverse event profile similar to profiles for atorvastatin 10-80 mg, simvastatin 10-80 mg, and pravastatin 10-40 mg.
Clinically significant elevations in alanine aminotransferase (more than 3 times the upper limit of normal on at least 2 consecutive occasions) were uncommon (0.2% or less) in the rosuvastatin and comparator statin groups. Elevated creatine kinase more than 10 times the upper limit of normal occurred in 0.3% or less of patients receiving rosuvastatin or other statins. Myopathy (creatine kinase more than 10 times the upper limit of normal with muscle symptoms) possibly related to treatment occurred in 0.03% of patients taking rosuvastatin at doses of 40 mg or less. The frequency of dipstick-positive proteinuria at rosuvastatin doses of 20 mg or less was comparable to that seen with other statins, and the development of proteinuria was not predictive of acute or progressive renal disease. Both short- and long-term rosuvastatin treatment were associated with small increases in estimated glomerular filtration rate, with improvements appearing to be somewhat greater in those patients beginning treatment with greater renal impairment. In the phase II-IV program, no deaths were attributed to rosuvastatin; at doses of rosuvastatin 40 mg or less, 1 case of rhabdomyolysis occurred in a patient who received rosuvastatin 20 mg and concomitant gemfibrozil treatment.