Discussion
These results suggest that many patients with a previous intolerance to statins can tolerate rosuvastatin EOD, attain significant LDL-C reductions, and achieve their LDL-C goal. Our findings are similar to previous data from case reports and small trials. We reported efficacy and improved tolerance with EOD statin dosing (rosuvastatin and atorvastatin) in a subset of patients who previously experienced myalgias with once-daily statin dosing.[16] Of the 15 patients who previously reported myalgias, 12 (80%) had a resolution of symptoms with EOD dosing. The 80% rate of tolerance in that investigation is similar to what we observed (72.5%; 37/51) in the present study. A recent case report involving 2 patients previously intolerant to atorvastatin indicated tolerance to rosuvastatin when dosed on Monday, Wednesday, and Friday, and LDL-C reductions of 20% and 38% after 6 weeks with 2.5-mg and 5-mg doses, respectively.[17] Lastly, we reported mean LDL-C reductions of 29% and tolerance in 80% of subjects (n = 10) previously intolerant to statin therapy when given rosuvastatin (mean dose 10 mg) once weekly.[18]
The average LDL-C reduction of 34.5% observed among the rosuvastatin EOD-tolerant group (mean dose 5.6 mg) in our study is consistent with the reduction shown in previous trials. Recently, a significant 39% reduction in LDL-C was achieved with rosuvastatin (10 mg) EOD among patients without a previous statin intolerance.[15] Further, we demonstrated similar LDL-C reductions (29%) in a subgroup of statin-intolerant patients who received either 5 or 10 mg of rosuvastatin EOD.[16] The doses of rosuvastatin used in our study were 2.5, 5, or 10 mg EOD (mean 5.6 mg). All doses used demonstrated significant LDL-C reductions; however, due to the small numbers in each subgroup, a comparative analysis was not performed.
We cannot specify why the EOD regimen was better tolerated by these patients. Possible explanations include the positive psychological effect of EOD treatment or lower plasma and muscle concentrations. Simply changing statins may also have contributed; Hansen et al.[19] reported that 43% of patients with previous statin-associated myopathy tolerated a different statin without a recurrence of symptoms. However, 4 patients in our study who had previously received rosuvastatin therapy daily and reported an adverse effect were able to tolerate the EOD regimen, thus making this explanation unlikely for all of the patients.
We elected to use rosuvastatin in an EOD regimen because its half-life of approximately 19 hours is the longest of available statins,[20] and it is the most potent statin at reducing LDL-C levels.[21] Atorvastatin also has a long half-life (~14 h) and has demonstrated effectiveness with EOD dosing.[16] Also, lovastatin, simvastatin, and atorvastatin are largely metabolized by CYP3A4, which is responsible for the conversion of many lipid-soluble agents to their hydrophilic forms for clearance and is a primary isoenzyme involved in many common drug interactions.[22] Rosuvastatin, in contrast, is primarily cleared renally and is minimally metabolized (<10%) by the less common CYP2C9 isoenzyme, and thus is potentially less likely to be implicated in common drug interactions.[22]
The Annals of Pharmacotherapy. 2008;42(3):341-346. © 2008 Harvey Whitney Books Company
Cite this: Effectiveness and Tolerability of Every-Other-Day Rosuvastatin Dosing in Patients with Prior Statin Intolerance - Medscape - Mar 01, 2008.
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