Genetic Determinants of Statin-Associated Myopathy

Molokhia, Mariam; Bhatia, Simmi; Nitsch, Dorothea

doi:10.2217/17410541.5.5.481

Cited by 5 publications

(1 citation statement)

References 62 publications

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“…The Primary Aims of the SACRED study are to test the hypotheses that statin therapy used in patients with compensated cirrhosis and clinically significant portal hypertension (CSPH) will reduce the incidence of hepatic decompensation, hepatocellular carcinoma and all-cause mortality. Secondary Aims include exploration of the interaction of SLCO1B1 genetic polymorphisms [ 35 ] (rs4149056) on safety and clinical efficacy of statin therapy in patients with compensated cirrhosis, and to assess the impact of statin exposure on health-related quality of life in patients with compensated cirrhosis.…”

Section: Introductionmentioning

confidence: 99%

SACRED: Effect of simvastatin on hepatic decompensation and death in subjects with high-risk compensated cirrhosis: Statins and Cirrhosis: Reducing Events of Decompensation

Kaplan

Mehta

García–Tsao

et al. 2021

Contemporary Clinical Trials

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Background/Aims: The development of decompensation in cirrhosis demarcates a marked change in the natural history of chronic liver disease. HMG-CoA reductase inhibitors (statins) exert pleiotropic effects that reduce inflammation and fibrosis as well as improve vascular reactivity. Retrospective studies uniformly have associated statin utilization with improved outcomes for patients with cirrhosis. Prospective human studies have shown that statins reduce portal hypertension and reduce death in patients with decompensated cirrhosis after variceal hemorrhage when added to standard therapy with an acceptable safety profile. This proposal aims to extend these findings to demonstrate that simvastatin reduces incident hepatic decompensation events among cirrhotic patients at high risk for hepatic decompensation. Methods: We will perform the SACRED Trial ( NCT03654053 ), a phase III, prospective, multi-center, double-blind, randomized clinical trial at 11 VA Medical Centers. Patients with compensated cirrhosis with clinically significant portal hypertension will be stratified based upon the concomitant use of nonselective beta-blockers and randomized to simvastatin 40 mg/day versus placebo for up to 24 months. Patients will be observed for the development of hepatic decompensation (variceal hemorrhage, ascites, encephalopathy), hepatocellular carcinoma, liver-related death, death from any cause, and/or complications of statin therapy. Ancillary studies will evaluate patient-reported outcomes and pharmacogenetic corollaries of safety and/or efficacy. Conclusion: Statins have a long track-record of safety and tolerability. This class of medications is generic and inexpensive, and thus, if the hypothesis is proven, there will be few barriers to widespread acceptance of the role of statins to prevent decompensation in patients with compensated cirrhosis. ClinicalTrials.gov Identifier: NCT03654053

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Section: Introductionmentioning

confidence: 99%

SACRED: Effect of simvastatin on hepatic decompensation and death in subjects with high-risk compensated cirrhosis: Statins and Cirrhosis: Reducing Events of Decompensation

Kaplan

Mehta

García–Tsao

et al. 2021

Contemporary Clinical Trials

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Current awareness: Pharmacoepidemiology and drug safety

2009

Pharmacoepidemiology and Drug

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In order to keep subscribers up‐to‐date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of pharmacoepidemiology and drug safety. Each bibliography is divided into 23 sections: 1 Reviews; 2 General; 3 Anti‐infective Agents; 4 Cardiovascular System Agents; 5 CNS Depressive Agents; 6 Non‐steroidal Anti‐inflammatory Agents; 7 CNS Agents; 8 Anti‐neoplastic Agents; 9 Haematological Agents; 10 Neuroregulator‐Blocking Agents; 11 Dermatological Agents; 12 Immunosuppressive Agents; 13 Autonomic Agents; 14 Respiratory System Agents; 15 Neuromuscular Agents; 16 Reproductive System Agents; 17 Gastrointestinal System Agents; 18 Anti‐inflammatory Agents ‐ Steroidal; 19 Teratogens/fetal exposure; 20 Antidiabetic Agents; 21 Contrast Agents; 22 Bone Conservation Agents; 23 Others. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted.

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Myopathy with statin–fibrate combination therapy: clinical considerations

Jacobson

2009

Nat Rev Endocrinol

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Many patients who receive statin therapy for hyperlipidemia-such as patients with diabetes mellitus and metabolic syndrome--have residual cardiovascular risk. These patients often have dyslipidemia, including low levels of HDL cholesterol and elevated levels of triglycerides and small, dense LDL. For such patients, combination treatment with statins and fibrates is a potentially useful strategy to improve lipid and lipoprotein profiles and reduce cardiovascular risk. However, statin-fibrate combination regimens have potential adverse effects on skeletal muscle, including myopathy. To date, no large-scale, prospective, randomized, controlled trial has evaluated the safety and efficacy of statin-fibrate combination therapy; one such trial is underway but will not report data until 2010. Until then, clinicians need to consider pharmacokinetic, pharmacodynamic, metabolic, pathophysiologic and other factors that can increase the systemic exposure of statins and/or fibrates and hence heighten the risk of toxic effects on muscles, as well as data from clinical trials and recommendations of consensus panels to optimize the safety of such combination regimens. On the basis of currently available data, fenofibrate or fenofibric acid is the fibrate of choice when used in combination with a statin because each is, in theory, associated with a lower risk of myopathy than gemfibrozil.

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Genetic Determinants of Statin-Associated Myopathy

Cited by 5 publications

References 62 publications

SACRED: Effect of simvastatin on hepatic decompensation and death in subjects with high-risk compensated cirrhosis: Statins and Cirrhosis: Reducing Events of Decompensation

SACRED: Effect of simvastatin on hepatic decompensation and death in subjects with high-risk compensated cirrhosis: Statins and Cirrhosis: Reducing Events of Decompensation

Current awareness: Pharmacoepidemiology and drug safety

Myopathy with statin–fibrate combination therapy: clinical considerations

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