initially increased LDL cholesterol in whom it would be unlikely, based on the baseline LDL Indirubin GSK-3 inhibitor cholesterol level, that the target LDL cholesterol of 70 mg/dl would be achieved by a high dose statin such as ATV80. It should be emphasized, however, that a target LDL cholesterol level 70 mg/dl in patients with acute coronary syndrome remains controversial15 and that in a large percentage of patients, a more moderate dose of a statin may be sufficient to decrease risk. Failure of the current use of statins, including ATV80, to lower the incidence of myocardial infarction, stroke, or short term mortality in patients with acute coronary syndrome15 suggests the need for further exploration of the effectiveness of more potent LDL cholesterol decreasing drugs.
Although a definitive conclusion on the comparative her2 review effectiveness of 2 agents such as RSV40 and ATV80 cannot be made without results from an adequately powered large scale randomized trial on clinical outcomes, the results of the present study evaluating several important lipid parameters, including LDL cholesterol and apolipoprotein B/apolipoprotein AI, provide a basis on which one might postulate an advantage of RSV40 compared with ATV80 and therefore undertake a larger scale, longer term clinical outcomes study. The significantly greater increase in HDL cholesterol with RSV40 compared with ATV80, beginning 2 weeks after randomization and persisting over the 12 week study period, also suggests an additional potential benefit of RSV40.
There is increasing evidence that an increase in HDL cholesterol may have important effects on oxidative stress, endothelial function, myocardial ischemia, plaque stability, and progression of atherosclerosis.16,17 The importance of this degree of increasing HDL cholesterol in terms of clinical outcome benefits must also await larger scale, longer term studies. With regard to the safety of statins in patients with acute coronary syndrome, the review by Morrissey et al15 emphasized an increased incidence of myopathy with high doses of simvastatin in the Aggrastat to Zocor 18 and Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine 19 trials. In the Pravastatin or Atorvastatin Evaluation and Infection Therapy trial,20 a high dose of atorvastatin was associated with a greater incidence of liver toxicity thanpravastatin 40 mg.
In the MIRACL study,3 the use of ATV80 was also associated with an increased incidence of liver enzyme abnormalities. Overall, however, ATV80 appears to be relatively well tolerated, with a 1.43% increase in liver enzyme abnormalities and 4 of 18,696 cases with a creatinine kinase increase 10 times the upper limit of normal.21 Similarly, previous experience with RSV20 and RSV40 has suggested that these doses are associated with a relatively low incidence of serious adverse events.22 In the present relatively small study, there was a trend toward a lower incidence of withdrawals owing to musculoskeletal and connective tissue disorders with the 2 doses of rosuvastatin, which should be interpreted in the context of the study,s open label design. The limitation of the study owing to an open label design should not bias its objective findings. Although the trial was open label, it was a prospective, randomized, observa