Statin Safety and Drug Interactions: Clinical Implications

Bottorff, Michael B.

doi:10.1016/j.amjcard.2005.12.007

Cited by 157 publications

(101 citation statements)

References 32 publications

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“…The risk of developing statin-associated myopathy has been reported to be exacerbated by a number of drugs that interfere with the metabolism of statins. [11][12][13][14] Because patients in our study were middle-aged and had multiple comorbidities, most were taking several drugs. About 40% of all patients with myopathy were taking corticosteroids or immunosuppressants, or both.…”

Section: Resultsmentioning

confidence: 99%

“…All statins are biotransformed in the liver, and drugs that interfere with this process may raise or lower the levels of these products in the blood. [11][12][13][14] Fibrates, warfarin, macrolid antibiotics, antifungal agents and immunosuppressants all predispose patients to myopathy. [11][12][13][14] In our study, there was no correlation between the extent of muscle damage and the use of any other single drug with a statin.…”

Section: Genementioning

confidence: 99%

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Association between statin-associated myopathy and skeletal muscle damage

Mohaupt¹,

Karas²,

Babiychuk³

et al. 2009

Canadian Medical Association Journal

141

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Section: Resultsmentioning

confidence: 99%

Section: Genementioning

confidence: 99%

Association between statin-associated myopathy and skeletal muscle damage

Mohaupt¹,

Karas²,

Babiychuk³

et al. 2009

Canadian Medical Association Journal

141

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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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“…This residual risk may relate to persistent abnormalities in TRLs and HDLs which are not fully corrected by statins [56,95]. Increasing statins may partially improve these lipoprotein abnormalities, but increases the risk of musculoskeletal side effects [96], to which diabetic patients are prone [6]. Evidence for the addition of ezetimibe, fibrates, niacin, and n-3 fatty acid ethyl esters as adjunctive treatments for residual dyslipidemia and CVD risk are discussed below.…”

Section: Addressing Residual Cardiovascular Risk With Combination Phamentioning

confidence: 99%

Atherogenic Dyslipidemia and Combination Pharmacotherapy in Diabetes: Recent Clinical Trials

Hamilton

Watts

2013

Rev Diabet Stud

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Patients with type 2 diabetes (T2D) are at a markedly increased risk of cardiovascular disease (CVD). Dyslipidemia is a common risk factor and a strong predictor of CVD in T2D patients. Although statins decrease the incidence of CVD in T2D, residual cardiovascular risk remains high despite the achievement of optimal or near-optimal plasma lowdensity lipoprotein (LDL) cholesterol concentrations. This may, in part, be due to uncorrected atherogenic dyslipidemia. Hypertriglyceridemia, the driving force behind diabetic dyslipidemia, results from hepatic overproduction and/or delayed clearance of triglyceride-rich lipoproteins. In patients treated with a statin to LDL-cholesterol goals, the addition of ezetimibe, fenofibrate, niacin, or n-3 fatty acid ethyl esters may be required to correct the persistent atherogenic dyslipidemia. Clinical trial evidence describing best practice is limited, but recent data supports the strategy of adding fenofibrate to a statin, and suggests specific benefits in dyslipidemic patients and in the improvement of diabetic retinopathy. However, based on results from a recent clinical trial, niacin should not be added to a statin in individuals with low high-density lipoprotein cholesterol and very well controlled LDL-cholesterol. Further evidence is required to support the role of ezetimibe and n-3 fatty acids in treating residual CVD risk in statin-treated T2D patients.

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Statin Safety and Drug Interactions: Clinical Implications

Cited by 157 publications

References 32 publications

Association between statin-associated myopathy and skeletal muscle damage

Association between statin-associated myopathy and skeletal muscle damage

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

Atherogenic Dyslipidemia and Combination Pharmacotherapy in Diabetes: Recent Clinical Trials

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