Long-term Safety of Hepatic Hydroxymethyl Glutaryl Coenzyme A Reductase Inhibitors

Bottorff, Michael B.; Hansten, Philip D.

doi:10.1001/archinte.160.15.2273

Cited by 122 publications

(93 citation statements)

References 29 publications

(39 reference statements)

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“…59 The safety of this family of drugs has been documented extensively and they are remarkably well tolerated. 21,22,39,55 Reports of minor adverse side-effects include constipation, flatulence, dyspepsia, nausea, gastrointestinal pain, and elevated serum transaminase levels. 22,59 The most serious adverse effect is myotoxicity including rhabdomyolysis which can be diminished with co-administration of ubiquinone.…”

Section: The Statin Family Of Drugsmentioning

confidence: 99%

“…22,59 The most serious adverse effect is myotoxicity including rhabdomyolysis which can be diminished with co-administration of ubiquinone. 55,59 Patients with hepatic insufficiency, cholestasis, or hepatic or renal diseases warrant careful monitoring when treated with statins. 57,59 In addition, drug:drug interactions must be thoroughly considered to ensure systemic concentrations are controlled.…”

Section: The Statin Family Of Drugsmentioning

confidence: 99%

“…This is of particular importance with agents that are also metabolized by cytochrome P450 3A4 such as gemfibrozil. 33,37,55,[60][61][62][63][64][65][66] Thus, the statins are functionally equivalent and the choice of drug is largely determined by individual patient needs and tolerability.…”

Section: The Statin Family Of Drugsmentioning

confidence: 99%

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HMG-CoA reductase inhibitors and the malignant cell: the statin family of drugs as triggers of tumor-specific apoptosis

et al. 2002

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The statin family of drugs target HMG-CoA reductase, the ratelimiting enzyme of the mevalonate pathway, and have been used successfully in the treatment of hypercholesterolemia for the past 15 years. Experimental evidence suggests this key biochemical pathway holds an important role in the carcinogenic process. Moreover, statin administration in vivo can provide an oncoprotective effect. Indeed, in vitro studies have shown the statins can trigger cells of certain tumor types, such as acute myelogenous leukemia, to undergo apoptosis in a sensitive and specific manner. Mechanistic studies show bcl-2 expression is down-regulated in transformed cells undergoing apoptosis in response to statin exposure. In addition, the apoptotic response is in part due to the depletion of the downstream product geranylgeranyl pyrophosphate, but not farnesyl pyrophosphate or other products of the mevalonate pathway including cholesterol. Clinically, preliminary phase I clinical trials have shown the achievable plasma concentration corresponds to the dose range that can trigger apoptosis of tumor types in vitro. Moreover, little toxicity was evident in vivo even at high concentrations. Clearly, additional clinical trials are warranted to further assess the safety and efficacy of statins as novel and immediately available anti-cancer agents. In this article, the experimental evidence supporting a role for the statin family of drugs to this new application will be reviewed.

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Section: The Statin Family Of Drugsmentioning

confidence: 99%

Section: The Statin Family Of Drugsmentioning

confidence: 99%

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HMG-CoA reductase inhibitors and the malignant cell: the statin family of drugs as triggers of tumor-specific apoptosis

et al. 2002

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“…7,15 When a drug inhibits another's metabolism, the resultant increase in concentration of the second drug can lead to adverse effects. 16 As statins become even more widely used, the potential for drug interactions will continue to increase.…”

Section: Statin Safety Issuesmentioning

confidence: 99%

Therapy to reduce risk of coronary heart disease

Rader¹

2003

Clinical Cardiology

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Summary: Recent primary and secondary intervention studies have shown that reduction of low-density lipoprotein cholesterol (LDL-C) with statins significantly reduced coronary heart disease (CHD) morbidity and mortality. However, many patients with dyslipidemia who have or are at risk for CHD do not reach target LDL-C goals. The recently updated National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III guidelines identify a group of patients at very high risk for CHD for more aggressive LDL-C reduction and reaffirm the importance of high-density lipoprotein cholesterol (HDL-C) by raising the categorical threshold to 40 mg/dl. Lipid-lowering therapy needs to be more aggressive in both primary and secondary prevention settings, and therapy should be considered to increase HDL-C as well as lower LDL-C in order to improve patient outcomes. Both combination therapy and the next generation of statins may provide improved efficacy across the dyslipidemia spectrum.

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“…8,12,13 Several medications have been identified that increase the risk of myopathy when administered concurrently with statins, primarily by decreasing the metabolism of the statin (Figure 2). 8,[14][15][16][17][18] Although these drug-drug interactions are well documented as increasing risk for myopathy, published studies documenting the frequency of prescribing interacting drugs are lacking. Einarson and colleagues 19 studied the extent of drug interactions and health care utilization in patients receiving statins.…”

mentioning

confidence: 99%

Frequency of Simvastatin Prescriptions With Potentially Interacting Medications in a Veterans Affairs Health Care System

Petropoulos¹,

Bello-Quintero²

2004

JMCP

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levated low-density lipoprotein (LDL) cholesterol has been identified as a primary risk-reduction target in patients at risk for coronary heart disease (CHD). Numerous epidemiological studies have demonstrated a relationship between elevated LDL and the incidence of CHD. Use of LDL-lowering therapy, including hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors, also known as statins (atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin, and simvastatin), has been shown to significantly reduce risk for major coronary events and coronary deaths. Statins are recommended as standard treatment for elevated LDL and are widely used in clinical practice. 1 Results from clinical trials with statins show a decrease in CHD and total mortality, revascularization procedures, and stroke. 2-6 A meta-analysis demonstrates a decrease of 31% in major coronary events and 21% in total mortality with use of statins compared with placebo. 7 Statins are generally well tolerated, with elevated liver enzymes and myopathy reported as the most common adverse effects. 8,9 Myopathy is a general term for muscle disease and includes myalgia, myositis, and rhabdomyolysis ( Figure 1). The prevalence of statin rhabdomyolysis is rare. A review of adverse drug events reported to the U.S. Food and Drug Administration (FDA) showed an overall reporting rate of 0.15 cases of fatal rhabdomyolysis per 1 million statin prescriptions. 10 However, the true incidence of statin rhabdomyolysis is unknown because of the underreporting of adverse drug reactions during the postmarketing period of medications. All statins seem to have a potential for causing rhabdomyolysis. The risk of myopathy is dose related and increases with statin serum concentration. 9,11 Most myopathy associated with statins occurs in patients of older age, small body frame, multisystem disease (including chronic renal insufficiency), multiple medications, perioperative periods, or specific drug-drug interactions. 8,12,13 Several medications have been identified that increase the risk of myopathy when administered concurrently with statins, primarily by decreasing the metabolism of the statin (Figure 2). 8,[14][15][16][17][18] Although these drug-drug interactions are well documented as increasing risk for myopathy, published studies documenting the frequency of prescribing interacting drugs are lacking. Einarson and colleagues 19 studied the extent of drug interactions and health care utilization in patients receiving statins. However, Einarson focused on concomitant drugs whose levels increased from the statin therapy and short-term concomitant therapy, which could increase statin serum concentrations.The primary objective of this review is to quantify the proportion of patients in a primary care setting on simvastatin, the ABSTRACT OBJECTIVE: The primary objective of this review is to quantify the proportion of patients on simvastatin, an HMG-CoA reductase inhibitor (commonly known as statin), who received concurrent prescriptions for potentially interacting c...

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Long-term Safety of Hepatic Hydroxymethyl Glutaryl Coenzyme A Reductase Inhibitors

Cited by 122 publications

References 29 publications

HMG-CoA reductase inhibitors and the malignant cell: the statin family of drugs as triggers of tumor-specific apoptosis

HMG-CoA reductase inhibitors and the malignant cell: the statin family of drugs as triggers of tumor-specific apoptosis

Therapy to reduce risk of coronary heart disease

Frequency of Simvastatin Prescriptions With Potentially Interacting Medications in a Veterans Affairs Health Care System

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