Monday, Wednesday, and Friday Dosing of Rosuvastatin in Patients Previously Intolerant to Statin Therapy

doi:10.1016/j.amjcard.2006.07.093

The American Journal of Cardiology

Volume 99, Issue 2, 15 January 2007, Page 291

https://doi.org/10.1016/j.amjcard.2006.07.093 Get rights and content

Statins are normally administered for the treatment of dyslipidemia on a daily basis. This standard dosing regimen is well tolerated by most patients. Occasionally, patients discontinue therapy secondary to side effects, most commonly myalgias. We describe 2 patients who were unable to tolerate daily atorvastatin therapy secondary to myalgias and were subsequently treated with rosuvastatin administered on Mondays, Wednesdays, and Fridays, with resolution of adverse effects. Significant reductions in serum low-density lipoprotein cholesterol levels were observed in the 2 patients despite the alternate-day dosing regimen. Rosuvastatin was chosen because of its long half-life (19 hours) and very high potency.

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Case Description

We describe 2 cases of women with goal low-density lipoprotein cholesterol levels of <130 mg/dl and 10-year Framingham risks of 15% and 5%, respectively, who were previously intolerant to atorvastatin therapy and were switched to rosuvastatin administered on Mondays, Wednesdays, and Fridays at 2.5 and 5 mg, respectively. The 2 patients’ lipid levels before the initiation of therapy and 6 weeks into therapy are listed in Table 1.

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Alternate-day dosing of statins may have a role in lipid-lowering therapy in select patients. Our case reports illustrate that Monday, Wednesday, and Friday dosing of rosuvastatin may provide an effective reduction in serum low-density lipoprotein cholesterol while avoiding the previously encountered side effects, specifically myalgias, with daily statin therapy. It is unclear if the absence of myalgias was secondary to a change in the specific statin, the decreased frequency of dosing, a

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Cited by (37)

Comprehensive review of statin-intolerance and the practical application of Bempedoic Acid
2024, Journal of Cardiology
Statin-intolerance (SI) has prevalence between 8.0 % and 10 %, and muscular complaints are the most common reason for discontinuation. Bempedoic acid (BA), an ATP citrate lyase inhibitor, decreases hepatic generation of cholesterol, upregulates low-density lipoprotein (LDL) receptor expression in the liver, and eventually clears circulating LDL-cholesterol from the blood. Multiple randomized clinical trials studying BA demonstrate a reduction in LDL levels by 17–28 % in SI. The CLEAR OUTCOME trial established significant cardiovascular benefits with BA. A dose of 180 mg/day of BA showed promising results. BA alone or in combination with ezetimibe is US Food and Drug Administration-approved for use in adults with heterozygous familial hypercholesterolemia and/or established atherosclerotic cardiovascular disease. BA reduced HbA1c by 0.12 % (p < 0.0001) in patients with diabetes. Adverse events of BA include myalgia (4.7 %), anemia (3.4 %), and increased aminotransferases (0.3 %). BA can cause up to four times higher risk of gout in those with a previous gout diagnosis or high serum uric acid levels. Reports of increased blood urea nitrogen and serum creatinine were noted. Current evidence does not demonstrate a reduction in deaths from cardiovascular causes. More studies that include a diverse population and patients with both high and low LDL levels should be conducted. We recommend that providers consider BA as an adjunct to statin therapy in patients with a maximally tolerated dosage to specifically target LDL levels.
Tolerability and effectiveness of every-other-day atorvastatin compared to daily atorvastatin in patients with muscle symptoms: A randomized controlled clinical trial
2020, Contemporary Clinical Trials Communications
Despite limited evidence, non-daily dosing of statins is recommended for managing muscle symptoms associated with statin therapy. We assessed the tolerability and effectiveness of every-other-day atorvastatin compared to daily atorvastatin in patients having muscle symptoms associated with atorvastatin therapy. A parallel-group, outcome-assessment-blinded, randomized controlled clinical trial was conducted at Colombo South Teaching Hospital, Sri Lanka. Patients with muscle pain, tenderness or cramps alone or in combination for ≥2 weeks while on daily atorvastatin for ≥1 month, with no alternative cause, were recruited. Patient's regular atorvastatin dose was given every-other-day to those in intervention group (IG) and daily to those in control group (CG). Primary outcomes were assessed at 24 weeks and included composite of myalgia and myositis, LDL-cholesterol level and percentage reduction of LDL-cholesterol from baseline. Number recruited was 49 to IG (women:79.6%; mean-age:60.6 ± 8.7years) and 52 to CG (women:73.1%; mean-age:61.7 ± 9.8years). Mean atorvastatin dose per day was 8.6 mg (SD = 4 mg) and 17.6 mg (SD = 8.4 mg) in IG and CG, respectively. Composite of myalgia and myositis at 24 weeks was 79.6% in IG and 69.2% in CG (OR = 1.7, 95% CI 0.7–4.3; p = 0.234). IG failed to show noninferiority for mean LDL-cholesterol (difference:0.31 mmol/L; upper limit 97.5% CI:0.61 mmol/L; p for noninferiority = 0.989) and for mean percentage reduction of LDL-cholesterol from baseline (difference:3.13%; upper limit 97.5% CI:15.5%; p for noninferiority = 0.718). At 24 weeks, mean creatine kinase and discomfort due to muscle symptoms (assessed with Visual Analogue Scale) were not different between the two groups. Findings of this study do not favor every-other-day atorvastatin as an option for managing patients with muscle symptoms associated with atorvastatin therapy.
Management strategies in patients with statin-associated muscle symptoms: What is the best strategy?
2016, Journal of Clinical Lipidology
Treatment strategies in patients with statin intolerance: The Cleveland Clinic experience
2013, American Heart Journal
Citation Excerpt :
Intermittent statin dosing is regarded as an interesting strategy in patients with statin-related symptoms. Nevertheless, most studies on the efficacy of this strategy are small.13–16,20,21 A recent review of several small studies by Marcus et al22 suggests that alternate-day dosing of statin may achieve similar levels of LDL-C reduction compared with daily dosing and may improve tolerance.
Statin therapy is a proven effective treatment of hyperlipidemia. However, a significant number of patients cannot tolerate statins. This study was conducted to review treatment strategies for patients intolerant to statin therapy with a focus on intermittent statin dosing.
We performed a retrospective analysis of medical records of 1,605 patients referred to the Cleveland Clinic Preventive Cardiology Section for statin intolerance between January 1995 and March 2010 with at least a 6-month follow-up. The changes in lipid profile, achievement of low-density lipoprotein cholesterol (LDL-C) goals, and statin tolerance rate were analyzed. Most (72.5%) of patients with prior statin intolerance were able to tolerate a statin for the median follow-up time of 31 months. Patients on intermittent statin dosing (n = 149) had significantly lower LDL-C reduction compared with daily dosing group (n = 1,014; 21.3% ± 4.0% vs 27.7% ± 1.4%, P < .04). However, compared with the statin discontinued group (n = 442), they had a significantly higher LDL-C reduction (21.3% ± 4.0% vs 8.3 ± 2.2%, P < .001), and a significantly higher portion achieved their Adult Treatment Panel III goal of LDL-C (61% vs 44%, P < .05). There was a trend toward a decrease in all-cause mortality at 8 years for patients on daily and intermittent statin dosing compared with those who discontinued statin (P = .08).
Most patients with previous statin intolerance can tolerate subsequent trial of statin. A strategy of intermittent statin dosing can be an effective therapeutic option in some patients and may result in reduction in LDL-C and achievement of LDL-C goals.
Efficacy and plasma drug concentrations with nondaily dosing of rosuvastatin
2013, Canadian Journal of Cardiology
Nondaily statin dosing is an alternative for patients unable to tolerate daily dosing. The higher potency and longer half-life of rosuvastatin lends itself to this regimen. The basis of this improved tolerability is not understood, but might be related to lower plasma drug concentrations. We examined the efficacy of nondaily rosuvastatin in previously statin-intolerant patients and determined plasma drug concentrations at various dose regimens.
A retrospective analysis at a specialty lipid clinic identified 58 patients eligible for evaluation after therapy with nondaily rosuvastatin. Plasma rosuvastatin levels were measured by liquid chromatography-mass spectrometry in 12 patients taking 10 mg nondaily rosuvastatin and in 11 and 12 age- and sex-matched patients taking 10 mg and 5 mg rosuvastatin daily, respectively. Whole body cholesterol synthesis was estimated from serum lathosterol measured by liquid chromatography-mass spectrometry.
In patients with a previous history of statin intolerance, nondaily rosuvastatin (average of 29.4 mg per week) lowered low-density lipoprotein cholesterol by 34.4 ± 21.3% (P < 0.001). Serum lathosterol levels were significantly higher in patients on nondaily regimens, as expected. However, mean plasma rosuvastatin levels of patients taking 10 mg nondaily did not significantly differ from those taking 10 mg daily.
In statin intolerant patients, nondaily rosuvastatin resulted in clinically relevant reductions in low-density lipoprotein cholesterol levels, with improved compliance. Whole body cholesterol synthesis was higher in patients taking nondaily rosuvastatin, but no differences in plasma drug concentrations were observed, suggesting that the improved tolerability was independent of plasma rosuvastatin levels.
La posologie non quotidienne des statines est une solution pour les patients incapables de tolérer la posologie quotidienne. La rosuvastatine qui a une activité thérapeutique plus élevée et une demi-vie plus longue se prête à ce schéma posologique. La base de cette meilleure tolérabilité n'est pas bien comprise, mais elle pourrait être liée à de plus faibles concentrations plasmatiques du médicament. Nous avons examiné l'efficacité de la rosuvastatine prise de manière non quotidienne chez les patients qui ont montré une intolérance aux statines et avons déterminé les concentrations plasmatiques du médicament à partir de schémas posologiques variés.
Une analyse rétrospective réalisée dans une clinique spécialisée des lipides a identifié 58 patients admissibles à l'évaluation après le traitement non quotidien par rosuvastatine. Les concentrations plasmatiques de la rosuvastatine ont été mesurées par la chromatographie en phase liquide et la spectrométrie de masse chez 12 patients prenant 10 mg quotidiennement de rosuvastatine, et chez 11 et 12 patients appariés selon l'âge et le sexe prenant respectivement 10 mg et 5 mg quotidiennement de rosuvastatine. La synthèse du cholestérol dans le corps entier a été estimée à partir du lathostérol sérique mesuré par la chromatographie en phase liquide et la spectrométrie de masse.
Chez les patients ayant des antécédents d'intolérance aux statines, la rosuvastatine prise de manière non quotidienne (moyenne de 29,4 mg par semaine) a abaissé le cholestérol à lipoprotéines de faible densité de 34,4 ± 21,3 % (P < 0,001). Conformément à nos attentes, les concentrations sériques de lathostérol ont été significativement plus élevées chez les patients suivant des schémas posologiques non quotidiens. Cependant, les concentrations plasmatiques moyennes des patients prenant 10 mg de manière non quotidienne n'ont pas significativement différé de ceux prenant 10 mg quotidiennement.
Chez les patients intolérants aux statines, la rosuvastatine prise de manière non quotidienne a entraîné des réductions cliniquement pertinentes des taux de cholestérol à lipoprotéines de faible densité et une meilleure observance. La synthèse du cholestérol dans le corps entier a été plus élevée chez les patients ne prenant pas la rosuvastatine de manière quotidienne, mais aucune différence dans les concentrations plasmatiques du médicament n'a été observée, ce qui suggère que la meilleure tolérabilité était indépendante des concentrations plasmatiques de la rosuvastatine.
Non-every day statin administration - A literature review
2012, European Journal of Internal Medicine
Citation Excerpt :
However, the heterogeneity of the study groups, medications and doses, design and aims precluded a pooled or meta-analysis. Fifteen studies reporting an alternate day statin treatment regimen were found [7–21]. Their design and details are provided in Table 1.
Statins are the treatment of choice for lowering LDL-C levels and reducing cardiovascular events. They have a remarkable safety profile, although some patients do not tolerate them. The aim of the study was to summarize the existing data on non-every day statin administration regimens.
We searched the MEDLINE databases to identify articles on non-every day statin administration, published between 1990 and January 2010. All publications regardless of methodology, design, size, or language were included. Data extracted included study design, duration and aims, type of statin, therapeutic regimen, patient characteristics, effectiveness, tolerability, and costs.
The 21 retrieved articles were characterized by small sample size, short follow up period, and a preponderance of males and “primary” prevention cases. Several lacked randomization or a control group. The heterogeneity of the study groups, medications, doses, design and aims precluded a pooled or meta-analysis. The most reported and effective regimens were atorvastatin and rosuvastatin on alternate days. These regimens, with or without other lipid lowering agents, were well tolerated even among subjects with previous statin intolerance, and produced meaningful cost savings. Nevertheless, the effectiveness of these regimens on cardiovascular events was not clarified.
Atorvastatin or rosuvastatin on alternate days might be considered for patients who are intolerant to statin therapy. Further studies are needed to evaluate the effect of these regimens on cardiovascular events.

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Case reportMonday, Wednesday, and Friday Dosing of Rosuvastatin in Patients Previously Intolerant to Statin Therapy

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Case report
Monday, Wednesday, and Friday Dosing of Rosuvastatin in Patients Previously Intolerant to Statin Therapy