Efficacy and Safety of Alternate-Day Versus Daily Dosing of Statins: a Systematic Review and Meta-Analysis

Awad, Kamal; Mikhailidis, Dimitri P.; Tóth, Peter P.; Jones, Steven R.; Moriarty, Patrick M.; Lip, Gregory Y.H.; Muntner, Paul; Catapano, Alberico L.; Pencina, Michael J.; Rosenson, Robert S.; Rysz, Jacek; Banach, Maciej

doi:10.1007/s10557-017-6743-0

Cited by 50 publications

(28 citation statements)

References 59 publications

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“…Physicians should address any side-effect–related concerns that patients have, and, if necessary, titrate the dose or switch to another statin [26]. Alternate-day dosing of statins is another option for patients with statin intolerance [27]. Cholesterol management guidelines recommend proactively screening for muscle issues prior to initiating and during statin therapy, including measuring creatine kinase levels in those at greatest risk, in order to proactively manage this side effect and distinguish from unrelated muscle issues to ensure continued persistence [1].…”

Section: Discussionmentioning

confidence: 99%

Long-term statin persistence is poor among high-risk patients with dyslipidemia: a real-world administrative claims analysis

et al. 2019

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Background: A decade ago, statin persistence was < 50% after 1 year, and recent short-term analyses have revealed very little progress in improving statin persistence, even in patients with a prior cardiovascular (CV) event. Data on longer-term statin persistence are lacking. We measured long-term statin persistence in patients with high CV risk. Methods: This retrospective administrative claims analysis of the Optum Research Database included patients aged ≥ 45 years with diabetes and/or atherosclerotic CV disease (ASCVD) who had a statin prescription filled in 2010. It included an elevated triglycerides (TG) cohort of patients with index date in 2010 and TG ≥ 150 mg/dL (n = 23,181) and a propensity-matched comparator cohort with TG < 150 mg/dL and high-density lipoprotein cholesterol > 40 mg/dL (n = 23,181). Both cohorts were followed for ≥ 6 months up to March 2016. Results: The probability of remaining on a prescription fill for index statin therapy was 47% after 1 year and 19% after 5 years in both cohorts. Statin persistence was worse among women than men, and among younger versus older patients (P < 0.001 for all comparisons). After 5 years, the probability of remaining on a prescription fill for index statin was < 25% across all subgroups assessed including patients with and without baseline revascularization, heart failure, peripheral artery disease and renal disease. Similar results were observed in a subcohort analysis of patients with TG 200-499 mg/dL. Conclusions: Long-term statin persistence after 5 years is alarmingly low (< 25%) and is a public health concern.

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Section: Discussionmentioning

confidence: 99%

Long-term statin persistence is poor among high-risk patients with dyslipidemia: a real-world administrative claims analysis

et al. 2019

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“…A meta-analysis of 12 RCTs and 1 quasi-RCT (n = 1023 patients) revealed no statistically significant difference between alternate-day and daily regimens of atorvastatin and rosuvastatin in terms of change in LDL-C and triglycerides, although daily regimens of atorvastatin and rosuvastatin were superior to alternate-day regimes for change in total cholesterol. In addition, there was no statistically significant difference between alternate-day and daily regimens on all lipid outcomes for both fluvastatin and pravastatin [75]. It should be noted that the majority of trials included in this meta-analysis used the same dose of statin (i.e., 10 mg both daily and on alternate days) so that alternate-day dosing resulted in a lower total weekly dose.…”

Section: What Are the Most Effective Treatment Strategies For Managinmentioning

confidence: 90%

Statin-Associated Muscle Disease: Advances in Diagnosis and Management

Taylor

Thompson

2018

Neurotherapeutics

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Since the first approval of lovastatin in 1987, hydroxy-methyl-glutaryl CoA (HMG CoA) reductase inhibitors, or statins, have been effective and widely popular cholesterol-lowering agents with substantial benefits for the prevention and treatment of cardiovascular disease. Not all patients can tolerate these drugs, however, and statin intolerance is most frequently associated with a range of side effects directed toward skeletal muscle, termed statin-associated muscle symptoms or SAMS. SAMS are particularly difficult to treat because there are no validated biomarkers or tests that can be used to confirm patient self-reports of SAMS, and a number of patients who report SAMS have non-specific muscle pain not attributable to statin therapy. This review summarizes the most recent evidence related to diagnosis and management of SAMS. First, the range of skeletal muscle side effects associated with statin therapy is described. Second, data regarding the incidence and prevalence of SAMS, the most frequently experienced muscle side effect, are presented. Third, the most promising new techniques to confirm diagnosis of SAMS are explored. Finally, the most effective strategies for the clinical management of SAMS are summarized. Better diagnostic and treatment strategies for SAMS will increase the number of patients using these life-saving statins, thereby increasing statin adherence and reducing the costs of avoidable cardiovascular events.

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“…Fluvastatin is one of several 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, cholesterol lowering agents that treat dyslipidaemia and prevent cardiovascular disease 42 . Statins work by competitive inhibition of HMG-CoA reductase, the rate-limiting step in cholesterol biosynthesis, causing reductions in cholesterol and low-density lipoproteins (LDL) and an increase in high-density lipoproteins (HDL), that carry cholesterol from other parts of the body to the liver for removal 42,43 . Fluvastatin is a good candidate for chemoprevention because it has a favorable safety profile and has been shown to have anti-cancer activity 43 .…”

Section: Discussionmentioning

confidence: 99%

“…Statins work by competitive inhibition of HMG-CoA reductase, the rate-limiting step in cholesterol biosynthesis, causing reductions in cholesterol and low-density lipoproteins (LDL) and an increase in high-density lipoproteins (HDL), that carry cholesterol from other parts of the body to the liver for removal 42,43 . Fluvastatin is a good candidate for chemoprevention because it has a favorable safety profile and has been shown to have anti-cancer activity 43 . Fluvastatin inhibits breast cancer cell proliferation and with a greater potency in estrogen receptor (ER) negative breast cancer cells 44,45 .…”

Section: Discussionmentioning

confidence: 99%

Identifying chemopreventive agents for obesity-associated cancers using an efficient, 3D high-throughput transformation assay

Benham¹,

Bullard²,

Dexheimer³

et al. 2019

Sci Rep

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Obesity is associated with ~40% of cancer diagnoses but there are currently no effective preventive strategies, illustrating a need for chemoprevention. We previously demonstrated that fibroblast growth factor 2 (FGF2) from adipose tissue stimulates malignant transformation, as measured by growth in soft agar, the gold-standard in vitro transformation assay. Because the soft agar assay is unsuitable for high throughput screens (HTS), we developed a novel method using 3D growth in ultra-low attachment conditions as an alternative to growth in agar to discover compounds that inhibit transformation. Treating non-tumorigenic, skin epithelial JB6 P + cells with FGF2 stimulates growth in ultra-low attachment conditions analogous to growth in the soft agar. This transformation HTS identified picropodophyllin, an insulin growth factor 1 receptor (IGF1R) inhibitor, and fluvastatin, an HMG-CoA reductase inhibitor, as potential chemopreventive agents. These compounds were validated for efficacy using two non-tumorigenic cell lines in soft agar. Another IGF1R inhibitor and other statins were also tested and several were able to inhibit growth in soft agar. This novel 3D HTS platform is fast, robust and has the potential to identify agents for obesity-associated cancer prevention.

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Efficacy and Safety of Alternate-Day Versus Daily Dosing of Statins: a Systematic Review and Meta-Analysis

Abstract: Alternate-day dosing of individual statins (especially atorvastatin and rosuvastatin) is as efficacious as daily dosing on LDL-C and TG.

Cited by 50 publications

References 59 publications

Long-term statin persistence is poor among high-risk patients with dyslipidemia: a real-world administrative claims analysis

Long-term statin persistence is poor among high-risk patients with dyslipidemia: a real-world administrative claims analysis

Statin-Associated Muscle Disease: Advances in Diagnosis and Management

Identifying chemopreventive agents for obesity-associated cancers using an efficient, 3D high-throughput transformation assay

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