Daily Dose versus Alternate-Day Dosing
Study Objective: To compare the efficacy of daily simvastatin administration with that of alternate-day therapy at double the daily dose.
Design: Nonrandomized, before-after comparison trial.
Setting: Outpatient clinic of a Veterans Affairs medical center.
Patients: Fifteen men with hyperlipidemia.
Intervention: The simvastatin regimen for patients with a low-density lipoprotein cholesterol (LDL) level at their established National Cholesterol Education Program goal was converted from daily dosing to double the daily dose given every other day for 8 weeks.
Measurements and Main Results: Baseline laboratory values were obtained for patients receiving daily simvastatin therapy. After 8 weeks of alternate-day therapy, follow-up laboratory values were obtained and assessed for efficacy and toxicity. The LDL-lowering effect of the daily dosing regimen was compared with that of the alternate-day dosing regimen. Paired t tests were computed to compare LDL concentrations before and after the study using a 95% confidence interval. No statistically significant difference was observed.
Conclusion: Alternate-day dosing of simvastatin may be an effective alternative to daily dosing.
The American Heart Association ranks cardiovascular disease as the leading cause of death in the United States. Reduction of low-density lipoprotein cholesterol (LDL) decreases the risk of cardiovascular disease and the frequency of cardiac and cerebrovascular events. Publication of the National Cholesterol Education Program (NCEP) guidelines for the management of hyperlipidemia has increased awareness of methods of primary and secondary prevention of cardiovascular events with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors. Subsequently, the cost of drug therapy increased.
Efficacy and safety of the HMG-CoA reductase inhibitor simvastatin in treating hyperlipidemia are well established. However, this well-proven efficacy comes with high acquisition costs for private-sector patients and for nonprofit organizations, such as the Bay Pines Veterans Affairs Medical Center (VAMC). Nonetheless, cost-effectiveness of simvastatin is based on reduction of total cost of hospital admissions and the cost/life-year saved in the treatment of patients after myocardial infarction or those with angina and/or diabetes.
Simvastatin is the drug with the highest total cost at Bay Pines VAMC. In an attempt to control cost without hindering therapeutic efficacy, Bay Pines VAMC and other VAMCs have implemented a tablet-splitting program. This cost-containment method can decrease the cost of drug therapy to an institution or a private-sector patient by up to 50% due to nonlinear cost/dose pricing of many drugs. A recent retrospective chart review performed at another VAMC showed that tablet splitting of simvastatin and atorvastatin was as effective as whole-tablet dosing for reduction of LDL and total cholesterol in patients with hypercholesterolemia.
Tablet splitting is accomplished by prescribing a drug at double strength with labeling that clearly instructs the patient to take half of a tablet to achieve the appropriate dose. Patients are given a tablet splitter and shown how to use it. Unfortunately, tablet splitting may not be feasible for patients who are visually, physically, or mentally impaired. Such patients, along with those who refuse to split tablets, may negatively affect intended therapeutic outcomes. These compliance issues generated interest in assessment of other methods for cost containment that would not hinder therapeutic efficacy or increase toxicity. Alternate-day dosing is one such method.
Evidence indicates that HMG-CoA reductase inhibitors given every other day are as effective at lowering LDL as daily dosing. One study evaluated the effects of alternate-day lovastatin dosing on serum lipoprotein levels. Twenty-one patients with an LDL level greater than 160 mg/dl were given lovastatin 20 mg every other day. After 6 weeks of therapy, it was discovered that 20 mg given every other day produced a 20% reduction in LDL. This study compared the efficacy of alternate-day lovastatin 20 mg to the results from daily therapy published in the Expanded Clinical Evaluation of Lovastatin study. The investigators concluded that lovastatin 20 mg administered every other day was slightly less effective than 20 mg administered daily. Another study assessed the efficacy of fluvastatin administered every other day versus an equivalent dose given daily. Patients were randomized to receive fluvastatin either 40 mg every other day or 20 mg/day for 6 weeks in a crossover fashion. The investigators concluded that fluvastatin 40 mg every other day and 20 mg every day resulted in comparable reductions in LDL.
Study Objective: To compare the efficacy of daily simvastatin administration with that of alternate-day therapy at double the daily dose.
Design: Nonrandomized, before-after comparison trial.
Setting: Outpatient clinic of a Veterans Affairs medical center.
Patients: Fifteen men with hyperlipidemia.
Intervention: The simvastatin regimen for patients with a low-density lipoprotein cholesterol (LDL) level at their established National Cholesterol Education Program goal was converted from daily dosing to double the daily dose given every other day for 8 weeks.
Measurements and Main Results: Baseline laboratory values were obtained for patients receiving daily simvastatin therapy. After 8 weeks of alternate-day therapy, follow-up laboratory values were obtained and assessed for efficacy and toxicity. The LDL-lowering effect of the daily dosing regimen was compared with that of the alternate-day dosing regimen. Paired t tests were computed to compare LDL concentrations before and after the study using a 95% confidence interval. No statistically significant difference was observed.
Conclusion: Alternate-day dosing of simvastatin may be an effective alternative to daily dosing.
The American Heart Association ranks cardiovascular disease as the leading cause of death in the United States. Reduction of low-density lipoprotein cholesterol (LDL) decreases the risk of cardiovascular disease and the frequency of cardiac and cerebrovascular events. Publication of the National Cholesterol Education Program (NCEP) guidelines for the management of hyperlipidemia has increased awareness of methods of primary and secondary prevention of cardiovascular events with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors. Subsequently, the cost of drug therapy increased.
Efficacy and safety of the HMG-CoA reductase inhibitor simvastatin in treating hyperlipidemia are well established. However, this well-proven efficacy comes with high acquisition costs for private-sector patients and for nonprofit organizations, such as the Bay Pines Veterans Affairs Medical Center (VAMC). Nonetheless, cost-effectiveness of simvastatin is based on reduction of total cost of hospital admissions and the cost/life-year saved in the treatment of patients after myocardial infarction or those with angina and/or diabetes.
Simvastatin is the drug with the highest total cost at Bay Pines VAMC. In an attempt to control cost without hindering therapeutic efficacy, Bay Pines VAMC and other VAMCs have implemented a tablet-splitting program. This cost-containment method can decrease the cost of drug therapy to an institution or a private-sector patient by up to 50% due to nonlinear cost/dose pricing of many drugs. A recent retrospective chart review performed at another VAMC showed that tablet splitting of simvastatin and atorvastatin was as effective as whole-tablet dosing for reduction of LDL and total cholesterol in patients with hypercholesterolemia.
Tablet splitting is accomplished by prescribing a drug at double strength with labeling that clearly instructs the patient to take half of a tablet to achieve the appropriate dose. Patients are given a tablet splitter and shown how to use it. Unfortunately, tablet splitting may not be feasible for patients who are visually, physically, or mentally impaired. Such patients, along with those who refuse to split tablets, may negatively affect intended therapeutic outcomes. These compliance issues generated interest in assessment of other methods for cost containment that would not hinder therapeutic efficacy or increase toxicity. Alternate-day dosing is one such method.
Evidence indicates that HMG-CoA reductase inhibitors given every other day are as effective at lowering LDL as daily dosing. One study evaluated the effects of alternate-day lovastatin dosing on serum lipoprotein levels. Twenty-one patients with an LDL level greater than 160 mg/dl were given lovastatin 20 mg every other day. After 6 weeks of therapy, it was discovered that 20 mg given every other day produced a 20% reduction in LDL. This study compared the efficacy of alternate-day lovastatin 20 mg to the results from daily therapy published in the Expanded Clinical Evaluation of Lovastatin study. The investigators concluded that lovastatin 20 mg administered every other day was slightly less effective than 20 mg administered daily. Another study assessed the efficacy of fluvastatin administered every other day versus an equivalent dose given daily. Patients were randomized to receive fluvastatin either 40 mg every other day or 20 mg/day for 6 weeks in a crossover fashion. The investigators concluded that fluvastatin 40 mg every other day and 20 mg every day resulted in comparable reductions in LDL.