Statin Medications


Article Author:
Omeed Sizar
Radia Jamil


Article Editor:
Raja Talati


Editors In Chief:
Michael Firstenberg
Lawrence Greiten


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Frank Smeeks
Kristina Soman-Faulkner
Trevor Nezwek
Radia Jamil
Patrick Le
Sobhan Daneshfar
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
6/1/2019 3:18:22 PM

Indications

Hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors, or statins, lower total cholesterol, low-density lipoprotein (LDL), and triglyceride concentrations while increasing high-density lipoprotein (HDL) concentrations. Statin medications have long been used for the treatment of hypercholesterolemia, hyperlipoproteinemia, and hypertriglyceridemia as an adjunct to diet and exercise. The primary use of these agents is for the primary and secondary prevention of coronary artery disease. The approved FDA indications vary slightly between the medications in this class but in general have recommendations for the treatment of atherosclerosis, myocardial infarction prophylaxis, and stroke prophylaxis. The choice of agent should be based on patient-specific characteristics, the pharmacokinetic profiles of each medication, and the 2013 American College of Cardiology/American Heart Association (ACC/AHA) Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults.[1][2][3]

Mechanism of Action

Statins are a selective, competitive inhibitor of hydroxymethylglutaryl-CoA (HMG-CoA) reductase, which is the enzyme responsible for the conversion of HMG-CoA to mevalonate in the cholesterol synthesis pathway. By reducing hepatic cholesterol synthesis, an upregulation of LDL-receptors and increased hepatic uptake of LDL-cholesterol from the circulation occurs.

Administration

Statin medications can be taken with or without food. Grapefruit juice should be avoided with some statins to minimize CYP3A4 interactions that could result in increased serum concentrations. Due to the diurnal variation in hepatic cholesterol synthesis, synthesis is highest in the early morning hours. An evening dose of some statins is recommended (e.g., fluvastatin, lovastatin, pravastatin, and simvastatin)[4]. Atorvastatin, pitavastatin, and rosuvastatin can be taken without regard to morning or evening administration, but they should be taken at the same time of day.

Adverse Effects

Statins are usually well tolerated with myopathy, rhabdomyolysis, hepatotoxicity, and diabetes mellitus being the most common adverse reactions. The incidence of myopathy is dose-dependent and may present as diffuse myalgias or otherwise unexplainable muscle tenderness or weakness with reversal upon medication discontinuation. Rhabdomyolysis is the most serious complication of statin use, but its occurrence is rare. Rarely, elevated hepatic transaminases have been observed. This is normally a transient effect and resolves with continued therapy or after brief therapy interruption. The FDA no longer supports liver function tests for monitoring the use of these medications without symptoms of hepatotoxicity such as unusual weakness or fatigue, jaundice, or dark-colored urine. [5][6][7]

Contraindications

Coadministration of CYP3A4 substrate statins (atorvastatin, lovastatin, and simvastatin) with medications that are strong 3A4 inhibitors (diltiazem, erythromycin, -azoles) may result in increased serum concentrations with increased risk of side effects. A reduced dose may be appropriate or a selection of an alternative statin that does not undergo metabolism via the 3A4 pathway. Administration with other drugs associated with myopathy should be done with caution.  Simvastatin and gemfibrozil coadministration is contraindicated because of the risk of rhabdomyolysis. Dose restrictions are recommended with the coadministration of gemfibrozil or other fibrates with statins, and the use of more than one statin is not recommended[8][9][10].

Statins are contraindicated for use by patients with an active hepatic disease or unexplained persistent elevations in aminotransferase levels. Statins are contraindicated in pregnancy and during breastfeeding because of the effects on the cholesterol pathway.  Cholesterol is an essential component for fetal and infant synthesis of steroids and cell membrane development.

Monitoring

Liver function tests should be assessed before therapy initiation as statins are contraindicated in patients with active hepatic disease. It is not required to schedule regular follow-up of liver function, unless clinical symptoms of hepatic disease become apparent. A baseline fasting lipid panel before initiation and a second lipid panel in 6 to 12 weeks should be compared to assess for efficacy and adherence.  Moderate-intensity therapy is expected to result in LDL reduction 30% to 50% from baseline and a high-intensity regimen a reduction of more than 50% from baseline. Assessments should be performed every 3 to 12 months after that as clinically indicated. Other than atorvastatin, statin medications have renal dosing guidelines which require assessment of serum creatinine and creatinine clearance.[11][12][13]

Toxicity

Statins are now well-established drugs with proven effectiveness for reduction of adverse cardiovascular and cerebrovascular events. There is no antidote to reverse the myopathy or rhabdomyolysis caused by statins. The general treatment is supportive and comprises immediate discontinuation of the offending drug. Aggressive fluid management is the cornerstone of treatment. The urine output needs to be monitored, and a Foley catheter insertion may be required. Other supportive measures include correction of any electrolyte disturbances and monitoring the patient with continuous ECG if hyperkalemia is present.

All patients need continual examination to monitor for hyperkalemia and acute renal failure. The patient may be discharged once electrolytes are normal and there is no renal dysfunction. The decision on restarting a statin requires good clinical judgment. Only the lowest dose of another statin should be used, and one should avoid concomitant use of fibrates. The patient should be closely monitored for muscle pain and routine urine and blood tests to ensure that muscle breakdown is not recurring. 

Enhancing Healthcare Team Outcomes

Statins have been around for about two decades and have proven effective at lowering cholesterol. When the patient has prescribed a statin, the nurse and pharmacist should educate the patient on the dose and side effects of the drugs. The pharmacist must regularly check the patient's list of medications to ensure safety and prevent polypharmacy interactions. Further, all patients prescribed statins should regularly have their liver function checked because these drugs are known to cause elevations in transaminases. Furthermore, statin therapy has been linked to an increased risk of diabetes with the first notable JUPITER trial published in 2008[14]. A meta-analysis study involving 91,140 patients published in 2014 showed a 9% increase in the likelihood of developing diabetes mellitus[15]. Studies have found that pitavastatin should be the drug of choice in pre-diabetic patients to reduce the risk of developing diabetes. The REAL-CAD trial published in 2018 found that a higher dose of pitavastatin significantly reduced cardiovascular events in Japanese patients with coronary artery disease when compared with a lower dose of pitavastin[16]. Recent updated meta-analysis showed that Coenzyme Q10 supplementation reduced statin-associated muscle symptoms.[17] Practitioners should consider coq10 supplementation before discontinuing statin medication. 

Outcomes

Many studies have been conducted on statins and shown them to be effective at lowering cholesterol and the risk of adverse cardiac events. The ALLHAT-LLT trial found no benefit in primary prevention of older adults above 75 years of age with statin therapy and hyperlipidemia[13]. Statin therapy should still be resumed in elderly patients with a history of coronary artery disease, stroke, and diabetes mellitus. (Level V)


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Statin Medications - Questions

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When a patient is prescribed a statin for lowering of lipids, what parameter should be monitored?



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Which agent blocks HMG CoA reductase?



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Which of the following medications is most likely to cause rhabdomyolysis?



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Statin drugs act by which of the following mechanisms?



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What is the side effect of greatest concern with the administration of statins?



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Which of the following statin drugs is indicated for use in HIV patients taking PI based medications?



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A 56-year-old male with a history of hypertension presents to the clinic for an annual physical. Annual labwork reviewed revealing elevated atherosclerotic vascular disease risk partially due to an LDL of 195 mg/dL and is started on a statin. Which of the following are common adverse effects of the new medication?



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Select the medication that can cause necrotizing myopathy.



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Which medication lowers serum C-reactive protein level?



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The Atorvastatin Versus Revascularization Treatment trial concluded all of the following?



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Which of the following was the conclusion of the Air Force/Texas Coronary Atherosclerosis Prevention Study regarding lovastatin?



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What did the West of Scotland Coronary Prevention Study demonstrate about pravastatin?



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A 61-year-old female presents for her yearly checkup. Her routine screening revealed that her cholesterol levels were abnormally elevated. She was started on a drug which competitively inhibits HMG CoA reductase. What is the most likely medication?



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A 45-year-old male with a history of coronary artery disease presents to for a follow-up visit. He had a drug eluting stent placed in his left anterior descending coronary artery 2 years ago for unstable angina. His most recent lipid panel results are as follows: total cholesterol 200 mg/dl, HDL 33 mg/dl, LDL 110 mg/dl, and triglycerides 200 mg/dl. He is on simvastatin 40 mg daily for dyslipidemia. In addition to intensifying dietary and lifestyle changes what changes in medical therapy should be recommended?



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A 52-year old obese male with a history of heart disease, hypertension, type 2 diabetes mellitus, arthritis, and gout is on allopurinol, metoprolol, furosemide, metformin, acarbose, and ibuprofen. His primary care physician has decided that he needs to be started on a statin to help lower the levels of low-density lipoprotein cholesterol. To avoid drug interactions when starting a statin, what should be considered?



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A frail elderly male patient is started on a statin to lower his cholesterol levels. The family is concerned about the serious side effects of the drug, like muscle breakdown. If muscle disease is to develop in such a patient, when does it usually present after starting therapy with a statin?



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In which of the following patient population do current USPSTF guidelines recommend that low to moderate dose statin for prevention of cardiovascular events should be started?



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How many patients must be treated with a statin to prevent a heart attack in one patient disease?



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Which of the following statements about statin drug class is incorrect?



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A male client who is obese and has diabetes mellitus is seen in the cardiology clinic. Blood work reveals that he has hyperlipidemia. The patient is prescribed an HMG CoA reductase inhibitor. Which of the following is an HMG CoA reductase inhibitor? Select all that apply.



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Statin Medications - References

References

Range JT,LaFontaine PR,Ryder PT,Polston M, Factors Associated With Adherence to Statin Medications of Patients Enrolled in a Self-insured University Health Plan. Clinical therapeutics. 2018 Sep 16     [PubMed]
Bakhai S,Bhardwaj A,Sandhu P,Reynolds JL, Optimisation of lipids for prevention of cardiovascular disease in a primary care. BMJ open quality. 2018     [PubMed]
Getting the most out of your heart medications. Harvard heart letter : from Harvard Medical School. 2018 Aug     [PubMed]
Brown AS,Watson KE, Statin Intolerance. Reviews in cardiovascular medicine. 2018     [PubMed]
Caughey GE,Gabb GM,Ronson S,Ward M,Beukelman T,Hill CL,Limaye V, Association of Statin Exposure With Histologically Confirmed Idiopathic Inflammatory Myositis in an Australian Population. JAMA internal medicine. 2018 Sep 1     [PubMed]
Chee WJ,Abdullahi H,Chan Y,Rattle A,Snedden S,Junckerstorff R, Retrospective Evaluation of Statin Prescription in the Elderly. Internal medicine journal. 2018 Jun 5     [PubMed]
Wilkins B,Hullikunte S,Simmonds M,Sasse A,Larsen PD,Harding SA, Improving the Prescribing Gap For Guideline Recommended Medications Post Myocardial Infarction. Heart, lung     [PubMed]
Lee JS,Gonzales R,Vittinghoff E,Corbett KK,Fleischmann KE,Sehgal N,Auerbach AD, Appropriate Reconciliation of Cardiovascular Medications After Elective Surgery and Postdischarge Acute Hospital and Ambulatory Visits. Journal of hospital medicine. 2017 Sep     [PubMed]
Arnold SV,Spertus JA,Tang F,Krumholz HM,Borden WB,Farmer SA,Ting HH,Chan PS, Statin use in outpatients with obstructive coronary artery disease. Circulation. 2011 Nov 29     [PubMed]
Coste J,Billionnet C,Rudnichi A,Pouchot J,Dray-Spira R,Giral P,Zureik M, Statins for primary prevention and rhabdomyolysis: A nationwide cohort study in France. European journal of preventive cardiology. 2018 Jan 1     [PubMed]
Moctezuma-Velázquez C,Abraldes JG,Montano-Loza AJ, The Use of Statins in Patients With Chronic Liver Disease and Cirrhosis. Current treatment options in gastroenterology. 2018 Jun     [PubMed]
Han BH,Sutin D,Williamson JD,Davis BR,Piller LB,Pervin H,Pressel SL,Blaum CS, Effect of Statin Treatment vs Usual Care on Primary Cardiovascular Prevention Among Older Adults: The ALLHAT-LLT Randomized Clinical Trial. JAMA internal medicine. 2017 Jul 1     [PubMed]
Ridker PM,Danielson E,Fonseca FA,Genest J,Gotto AM Jr,Kastelein JJ,Koenig W,Libby P,Lorenzatti AJ,MacFadyen JG,Nordestgaard BG,Shepherd J,Willerson JT,Glynn RJ, Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. The New England journal of medicine. 2008 Nov 20     [PubMed]
Chogtu B,Magazine R,Bairy KL, Statin use and risk of diabetes mellitus. World journal of diabetes. 2015 Mar 15     [PubMed]
Taguchi I,Iimuro S,Iwata H,Takashima H,Abe M,Amiya E,Ogawa T,Ozaki Y,Sakuma I,Nakagawa Y,Hibi K,Hiro T,Fukumoto Y,Hokimoto S,Miyauchi K,Yamazaki T,Ito H,Otsuji Y,Kimura K,Takahashi J,Hirayama A,Yokoi H,Kitagawa K,Urabe T,Okada Y,Terayama Y,Toyoda K,Nagao T,Matsumoto M,Ohashi Y,Kaneko T,Fujita R,Ohtsu H,Ogawa H,Daida H,Shimokawa H,Saito Y,Kimura T,Inoue T,Matsuzaki M,Nagai R, High-Dose Versus Low-Dose Pitavastatin in Japanese Patients With Stable Coronary Artery Disease (REAL-CAD): A Randomized Superiority Trial. Circulation. 2018 May 8     [PubMed]
Kamal SM, Effects of single-dose morning and evening administration of pravastatin on antioxidant markers in cholesterol-fed rabbits. Journal of experimental pharmacology. 2011     [PubMed]
Qu H,Guo M,Chai H,Wang WT,Gao ZY,Shi DZ, Effects of Coenzyme Q10 on Statin-Induced Myopathy: An Updated Meta-Analysis of Randomized Controlled Trials. Journal of the American Heart Association. 2018 Oct 2;     [PubMed]

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