Statin Safety: An Assessment Using an Administrative Claims Database

Cziraky, Mark J.; Willey, Vincent J.; McKenney, James M.; Kamat, Siddhesh; Fisher, Mary L.; Guyton, John R.; Jacobson, Terry A.; Davidson, Michael

doi:10.1016/j.amjcard.2005.12.011

Cited by 117 publications

(78 citation statements)

References 22 publications

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“…Concomitant use of CYP3A4 inhibitors and simvastatin is associated with an increased risk of developing myopathy and rhabdomyolysis [8,10,15,29,30]. In 2006 the most frequent combination overall was simvastatin/ erythromycin, and the number of patients exposed to this combination more than doubled from 2004 to 2006.…”

Section: Discussionmentioning

confidence: 99%

Co‐medication of statins and CYP3A4 inhibitors before and after introduction of new reimbursement policy

Devold

Molden

Furu

2009

Brit J Clinical Pharma

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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • HMG‐CoA reductase inhibitors (statins) are frequently used drugs in the treatment of dyslipidaemia. • Co‐medication with interacting drugs increases the risk of statin‐induced muscular side‐effects. • Simvastatin exhibits particularly high interaction potential due to substantial metabolism via cytochrome P450 3A4 (CYP3A4). WHAT THIS STUDY ADDS • In June 2005, a new reimbursement policy was introduced by the Norwegian Medicines Agency stating that simvastatin should be prescribed as first‐line lipid‐lowering therapy. • Following introduction of the new policy, the number of patients co‐medicated with simvastatin and CYP3A4 inhibitors almost doubled. • A potential consequence is increased incidence of muscular side‐effects in the statin‐treated population. AIMS To assess the prevalence of co‐medication of statins and CYP3A4 inhibitors before and after introduction of a new Norwegian reimbursement policy, which states that all patients should be prescribed simvastatin as first‐line lipid‐lowering therapy. METHODS Data from patients receiving simvastatin, lovastatin, pravastatin, fluvastatin or atorvastatin in 2004 and 2006, including co‐medication of potent CYP3A4 inhibitors, were retrieved from the Norwegian Prescription Database covering the total population of Norway. Key measurements were prevalence of continuous statin use (two or more prescriptions on one statin) and proportions of different statin types among all patients and those co‐medicated with CYP3A4 inhibitors. RESULTS In 2004, 5.9% (n= 272 342) of the Norwegian population received two or more prescriptions on one statin compared with 7.0% (n= 324 267) in 2006. The relative number of simvastatin users increased from 39.7% (n= 112 122) in 2004 to 63.1% (n= 226 672) in 2006. A parallel increase was observed within the subpopulation co‐medicated with statins and CYP3A4 inhibitors, i.e. from 42.9% (n= 7706) in 2004 to 63.6% (n= 13 367) in 2006. For all other statins the number of overall users decreased to a similar extent to those co‐medicated with CYP3A4 inhibitors. CONCLUSIONS In both 2004 and 2006, the choice of statin type did not depend on whether the patient used a CYP3A4 inhibitor or not. Considering the pronounced interaction potential of simvastatin with CYP3A4 inhibitors, a negative influence of the new policy on overall statin safety seems likely.

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Section: Discussionmentioning

confidence: 99%

Co‐medication of statins and CYP3A4 inhibitors before and after introduction of new reimbursement policy

Devold

Molden

Furu

2009

Brit J Clinical Pharma

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“…234,235 The increased risk for myopathy with nicotinic acid has been debated, but in recent reviews no increased risk of myopathy was found with this agent. 236,237 6.2 Bile acid sequestrants 6.2.1 Mechanism of action Bile acids are synthesized in the liver from cholesterol and are released into the intestinal lumen, but most of the bile acid is returned to the liver from the terminal ileum via active absorption. The two older bile acid sequestrants, cholestyramine and colestipol, are both bile acid-binding exchange resins.…”

Section: Interactionsmentioning

confidence: 99%

ESC/EAS Guidelines for the management of dyslipidaemias

Catapano¹,

Reiner²,

Backer³

et al. 2011

Atherosclerosis

565

189

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“…The incidence of drug-related myopathy requiring hospitalization is low for all currently marketed statins (Cziraky et al, 2006). However, before its voluntary withdrawal from the market in 2001, cerivastatin was clearly over-represented among cases of statin-associated rhabdomyolysis, demonstrating differences in safety among statins (Wooltorton, 2001).…”

mentioning

confidence: 99%

The Guinea Pig as a Preclinical Model for Demonstrating the Efficacy and Safety of Statins

Madsen

Janovitz²,

Zhang³

et al. 2007

J Pharmacol Exp Ther

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Statins, because of their excellent efficacy and manageable safety profile, represent a key component in the current armamentarium for the treatment of hypercholesterolemia. Nonetheless, myopathy remains a safety concern for this important drug class. Cerivastatin was withdrawn from the market for myotoxicity safety concerns. BMS-423526 ,5-dihydroxy-heptenoic acid} sodium salt], similar to cerivastatin in potency and lipophilicity, was terminated in early clinical development due to an unacceptable myotoxicity profile. In this report, we describe the guinea pig as a model of statin-induced cholesterol lowering and myotoxicity and show that this model can distinguish statins with unacceptable myotoxicity profiles from statins with acceptable safety profiles. In our guinea pig model, both cerivastatin and BMS-423526 induced myotoxicity at doses near the ED 50 for total cholesterol (TC) lowering in plasma. In contrast, wide differences between myotoxic and TC-lowering doses were established for the currently marketed, more hydrophilic statins, pravastatin, rosuvastatin, and atorvastatin. This in vivo model compared favorably to an in vitro model, which used statin inhibition of cholesterol synthesis in rat hepatocytes and L6 myoblasts as surrogates of potential efficacy and toxicity, respectively. Our conclusion is that the guinea pig is a useful preclinical in vivo model for demonstrating whether a statin is likely to have an acceptable therapeutic safety margin.

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Statin Safety: An Assessment Using an Administrative Claims Database

Cited by 117 publications

References 22 publications

Co‐medication of statins and CYP3A4 inhibitors before and after introduction of new reimbursement policy

Co‐medication of statins and CYP3A4 inhibitors before and after introduction of new reimbursement policy

ESC/EAS Guidelines for the management of dyslipidaemias

The Guinea Pig as a Preclinical Model for Demonstrating the Efficacy and Safety of Statins

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