Every-Other-Day Rosuvastatin Dosing in Patients with Statin Intolerance
Every-Other-Day Rosuvastatin Dosing in Patients with Statin Intolerance
Background: Statins are generally well tolerated, but some patients discontinue therapy secondary to adverse effects. Dosing a statin (rosuvastatin) every other day (EOD) may provide significant lipoprotein changes while avoiding common adverse effects in this statin-intolerant population.
Objective: To determine the effect and tolerance of EOD rosuvastatin in patients previously intolerant to statin therapy.
Methods: We performed a retrospective analysis of patients treated with EOD rosuvastatin at 2 lipid specialty clinics: the University of Kansas Lipid, Atherosclerosis, and LDL-Apheresis Center and the Hartford Hospital Cholesterol Management Center. Approximately 2600 charts were reviewed to identify patients receiving rosuvastatin EOD who previously had experienced statin intolerance. Fifty-one patients were eligible for the analysis, which evaluated changes in the lipid profile, the number achieving their low-density lipoprotein cholesterol (LDL-C) goals, and the percent tolerating rosuvastatin EOD. Laboratory data were assessed immediately prior to rosuvastatin EOD therapy and at the first follow-up.
Results: Myalgias (76.5%) and increased transaminase levels (19.5%) were the most common causes of prior statin intolerance, but 72.5% (37/51) of patients were able to tolerate the EOD therapy (mean dose 5.6 mg) regimen for 4 ± 2.9 (mean ± SD) months. Mean LDL-C decreased 34.5% (p < 0.001) in the patients who tolerated the regimen, enabling approximately 50% to achieve their LDL-C goal. All patients who were considered to be intolerant to rosuvastatin EOD therapy (27.5%; 14/51) reexperienced the symptoms of their prior statin intolerance.
Conclusions: Treating patients intolerant to statins with rosuvastatin EOD was tolerated by the majority of patients and reduced LDL-C in our study. This dosing strategy may be useful in patients intolerant to once-daily statin dosing, although such an approach has not been documented to reduce cardiovascular events.
Hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) are well established as treatment for lowering low-density lipoprotein cholesterol (LDL-C) and reducing cardiovascular events. Overall, these agents have a remarkable safety profile, although some patients are intolerant of them.
Common reasons for discontinuation of statin therapy include elevated hepatic enzyme levels, gastrointestinal complaints, and "statin myopathy," which includes myalgia, weakness, cramping, and rhabdomyolysis. Nonspecific muscle complaints or joint pain without elevated creatine kinase levels have been reported in approximately 5% of clinical trial participants; however, the range is wide (0.3-33%). An observational study, the PRIMO (Prediction of Muscular Risk in Observational conditions), reported muscle complaints in 10.5% of the 7924 statin-treated subjects, suggesting that statin-induced myopathy is considerably more frequent in clinical practice.
A number of other drugs (eg, bile acid resins, ezetimibe, niacin) are available to reduce LDL-C in patients who are statin intolerant; however, these agents are less effective compared with statin therapy. Moreover, the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP-III) Update emphasized LDL-C reductions of at least 30-40% and the option of more aggressive LDL-C goals for patients considered at high-risk for a cardiovascular event. These factors produce the common clinical challenge of achieving an aggressive LDL-C goal in a high-risk patient intolerant to statin therapy. Thus, additional options are essential for patients unable to tolerate typical statin dosing in order to achieve the desired LDL-C goal.
The myalgias and elevation in hepatic enzymes caused by statin therapy are considered to be dose-dependent adverse effects. Additionally, moderate-to-high statin doses possess a rather flat dose response relative to low doses. The lowest approved daily doses of statins will typically reduce LDL-C by 20-40% compared with moderate and high doses, which achieve only an additional 6% LDL-C reduction with each doubling of dose. We theorized that by using low doses of a statin (rosuvastatin) every other day (EOD), a significant LDL-C reduction may still be achieved while also avoiding the dose-dependent adverse effects. Rosuvastatin appears to be a rational choice for markedly improving lipoprotein levels in statin-intolerant patients because of its high potency, long half-life, and lack of CYP3A4 metabolism.
Studies evaluating the effect and tolerance of alternative statin dosing are limited. A number of trials have demonstrated efficacy with alternate-day statin dosing, including rosuvastatin; however, the study populations included patients without previous intolerance to statins. A few anecdotal case reports have described efficacy and improved tolerance of rosuvastatin when dosed once weekly and thrice weekly. We previously reported on a subgroup of patients who demonstrated significant LDL-C reductions and better tolerance with EOD statin dosing, but the sample was small and included both atorvastatin and rosuvastatin. The study reported here examined the effect and tolerance of EOD rosuvastatin therapy in a considerably larger cohort.
Background: Statins are generally well tolerated, but some patients discontinue therapy secondary to adverse effects. Dosing a statin (rosuvastatin) every other day (EOD) may provide significant lipoprotein changes while avoiding common adverse effects in this statin-intolerant population.
Objective: To determine the effect and tolerance of EOD rosuvastatin in patients previously intolerant to statin therapy.
Methods: We performed a retrospective analysis of patients treated with EOD rosuvastatin at 2 lipid specialty clinics: the University of Kansas Lipid, Atherosclerosis, and LDL-Apheresis Center and the Hartford Hospital Cholesterol Management Center. Approximately 2600 charts were reviewed to identify patients receiving rosuvastatin EOD who previously had experienced statin intolerance. Fifty-one patients were eligible for the analysis, which evaluated changes in the lipid profile, the number achieving their low-density lipoprotein cholesterol (LDL-C) goals, and the percent tolerating rosuvastatin EOD. Laboratory data were assessed immediately prior to rosuvastatin EOD therapy and at the first follow-up.
Results: Myalgias (76.5%) and increased transaminase levels (19.5%) were the most common causes of prior statin intolerance, but 72.5% (37/51) of patients were able to tolerate the EOD therapy (mean dose 5.6 mg) regimen for 4 ± 2.9 (mean ± SD) months. Mean LDL-C decreased 34.5% (p < 0.001) in the patients who tolerated the regimen, enabling approximately 50% to achieve their LDL-C goal. All patients who were considered to be intolerant to rosuvastatin EOD therapy (27.5%; 14/51) reexperienced the symptoms of their prior statin intolerance.
Conclusions: Treating patients intolerant to statins with rosuvastatin EOD was tolerated by the majority of patients and reduced LDL-C in our study. This dosing strategy may be useful in patients intolerant to once-daily statin dosing, although such an approach has not been documented to reduce cardiovascular events.
Hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) are well established as treatment for lowering low-density lipoprotein cholesterol (LDL-C) and reducing cardiovascular events. Overall, these agents have a remarkable safety profile, although some patients are intolerant of them.
Common reasons for discontinuation of statin therapy include elevated hepatic enzyme levels, gastrointestinal complaints, and "statin myopathy," which includes myalgia, weakness, cramping, and rhabdomyolysis. Nonspecific muscle complaints or joint pain without elevated creatine kinase levels have been reported in approximately 5% of clinical trial participants; however, the range is wide (0.3-33%). An observational study, the PRIMO (Prediction of Muscular Risk in Observational conditions), reported muscle complaints in 10.5% of the 7924 statin-treated subjects, suggesting that statin-induced myopathy is considerably more frequent in clinical practice.
A number of other drugs (eg, bile acid resins, ezetimibe, niacin) are available to reduce LDL-C in patients who are statin intolerant; however, these agents are less effective compared with statin therapy. Moreover, the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP-III) Update emphasized LDL-C reductions of at least 30-40% and the option of more aggressive LDL-C goals for patients considered at high-risk for a cardiovascular event. These factors produce the common clinical challenge of achieving an aggressive LDL-C goal in a high-risk patient intolerant to statin therapy. Thus, additional options are essential for patients unable to tolerate typical statin dosing in order to achieve the desired LDL-C goal.
The myalgias and elevation in hepatic enzymes caused by statin therapy are considered to be dose-dependent adverse effects. Additionally, moderate-to-high statin doses possess a rather flat dose response relative to low doses. The lowest approved daily doses of statins will typically reduce LDL-C by 20-40% compared with moderate and high doses, which achieve only an additional 6% LDL-C reduction with each doubling of dose. We theorized that by using low doses of a statin (rosuvastatin) every other day (EOD), a significant LDL-C reduction may still be achieved while also avoiding the dose-dependent adverse effects. Rosuvastatin appears to be a rational choice for markedly improving lipoprotein levels in statin-intolerant patients because of its high potency, long half-life, and lack of CYP3A4 metabolism.
Studies evaluating the effect and tolerance of alternative statin dosing are limited. A number of trials have demonstrated efficacy with alternate-day statin dosing, including rosuvastatin; however, the study populations included patients without previous intolerance to statins. A few anecdotal case reports have described efficacy and improved tolerance of rosuvastatin when dosed once weekly and thrice weekly. We previously reported on a subgroup of patients who demonstrated significant LDL-C reductions and better tolerance with EOD statin dosing, but the sample was small and included both atorvastatin and rosuvastatin. The study reported here examined the effect and tolerance of EOD rosuvastatin therapy in a considerably larger cohort.
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