Download Dyslipidemia Management for APRNs

Dyslipidemia Management for APRNs
This course has been awarded
one (1.0) contact hour.
This course expires on March 24, 2017.
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First Published: March 24, 2014
Acknowledgements
RN.com acknowledges the valuable contributions of…
...Darrell Hulisz, RPh, PharmD, an Associate Professor of Family Medicine and Community Health
in the School of Medicine at Case Western Reserve University, Cleveland, OH. He also holds a
clinical faculty appointment at Ohio Northern University, College of Pharmacy. Dr. ("Darrell") Hulisz
received his BS in Pharmacy from the University of Toledo and Doctor of Pharmacy from the Medical
University of South Carolina.
Darrell has published over 70 papers in the medical and pharmacy literature, has lectured extensively
both locally and nationally and has served as an investigator in several clinical trials. He has made
numerous appearances on local television and radio programs. He also serves on several national
advisory panels and is an author for WebMD’s Medscape.com and a speaker and author for AMN
Healthcare's RxSchool.com.
Darrell currently practices as a clinical pharmacist with University Hospitals, Case Medical Center,
Family Medicine Residency Program, where he works in consultation with family physicians, both on
inpatient and outpatient services. Darrell has been the recipient of multiple teaching awards. He also
completed a federal, multi-agency faculty development fellowship to further his expertise in the field of
addiction medicine. He also served as a co-investigator for a multidisciplinary chronic pain study
funded by the Macy Foundation. He was recently awarded a federal grant as a co-investigator to
develop leadership and advocacy in urban health and community health within a multidisciplinary
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team.
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The author of this course does not have any conflict of interest to declare.
The planners of the educational activity have no conflicts of interest to disclose.
There is no commercial support being used for this course.
Purpose and Objectives
The purpose of this one contact hour course on dyslipidemia management is to provide the APRN
with an advanced knowledge of latest pharmaceutical management therapies available for the control
of this disorder.
After successful completion of this continuing education course, the APRN will be able to:
1. Describe the epidemiology of dyslipidemia with respect to prevalence and associated risks
2. Explain the pathogenesis and basic pathophysiology of dyslipidemia
3. Understand the national consensus guidelines on pharmacological management of patients with
dyslipidemia
4. Identify medications that can exacerbate or complicate the management of patients with
dyslipidemia
5. Discuss the most common clinical scenarios where certain medications may be preferred or
contraindicated when used to treat dyslipidemia
6. List the most common modifiable cardiovascular risk factors that should be addressed in all
patients
Introduction
Cardiovascular disease (CVD) is the number one health problem of men and women in the U.S.,
accounting for 973,000 hospitalizations for myocardial infarction alone. The estimated incidence of
new heart attacks is approximately 565,000. New strokes occur in about 500,000 people annually.
Dyslipidemia is an abnormal amount of lipids (e.g. cholesterol and/or fat) in the blood. In developed
countries, most dyslipidemias are hyperlipidemias (elevated lipids in the blood). This is often due to
diet and lifestyle.
The importance of treating dyslipidemias based on cardiovascular risk factors is highlighted by the
National Cholesterol Education Program guidelines. The Adult Treatment Panel (ATP-III) issued
expert panel recommendations on treating dyslipidemia in 2001. These guidelines were updated in
2004. In November 2013, guidelines from the American College of Cardiology and American Heart
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Association were developed in conjunction with the National Heart, Lung and Blood Institute (NHLBI)
and published online. Highlights from these guidelines will be summarized herein.
Coronary heart disease (CHD) accounts for $142.1 billion and stroke accounts for $56.8 billion
annually.
Epidemiology of Cardiovascular Disease
Dyslipidemia is the most important modifiable risk factors for CVD. However, even when patients are
treated to established low density lipoprotein (LDL) goals, risk reductions for acute CHD events are
reduced by only 20-35%.
Only about 50% of patients with CVD have dyslipidemia; other biochemical markers are emerging
such as C-reactive protein, homocysteine, Apolipoprotien B, and Lipoprotein(a).
The evidence in support of lipid lowering therapy is far more compelling for secondary versus primary
prevention.
(Carroll et al., 2013, Smith et al., 2006)
Many patients with CHD and dyslipidemia are sub-optimally treated or aren’t achieving LDL
goals.
Incidence of hypercholesterolemia
In 2011–2012, an estimated 12.9% of U.S. adults aged 20 and older (11.1% of men and 14.4% of
women) had high total cholesterol, which is mostly unchanged since 2009–2010.
Approximately 17% of adults had low high-density lipoprotein (HDL) cholesterol during 2011–2012. A
positive change is that the percentage of adults with low HDL levels has decreased 20% since 2009–
2010.
Approximately 70% of adults (67% of men and nearly 72% of women) had been screened for total
cholesterol during 2011-2012.
(Carroll et al, 2013; Smith et al., 2006)
CHD Risk Factors
Modifiable
• Dyslipidemia
•
Elevated LDL
•
Low HDL
•
Elevated TG
•
Cigarette smoking
•
Hypertension
•
Diabetes mellitus
•
Obesity
•
Atherogenic diet
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•
Thrombogenic factors
•
Sedentary lifestyle
Nonmodifiable
• Advancing age
•
Men ≥45 years
•
Women ≥55 years
•
Male gender
•
Family history of premature CHD
Cholesterol Screening
Basic screening recommendations from the Adult Treatment Panel (ATP-III) include the following:
•
Total cholesterol (TC) alone not recommended as initial test
•
In those age 20 and older, fasting TC, LDL, HDL and triglycerides (TG) are recommended every
five years
•
If patients are not fasting, then only TC and HDL should be regarded; if TC>200 or HDL <40, then
a full lipoprotein profile is recommended
•
The LDL level and CV risk factors are used to guide therapy
•
LDL <100 is optimal in secondary prevention, but was later revised to a target of LDL < 70 in high
risk patients
(Expert Panel on Detection Evaluation, and Treatment of High Blood Cholesterol in Adults, 2001,
2001; Grundy et al., 2004)
Summary of CV Risk Factors
The risk factors that are used to guide treatment include:
•
Age: males 45 and older, females 55 or older
•
Family history of premature CHD in a 1st-degree relative with male relative <55 years old and
female relative <65 years
•
History of hypertension, as defined as >140/90mmHg or currently receiving blood pressure
lowering medications
•
History of active cigarette smoking
•
An HDL of < 40mg/dL
•
CVD present or having diabetes
(Expert Panel on Detection Evaluation, and Treatment of High Blood Cholesterol in Adults, 2001)
Test Yourself
The evidence supporting lipid lowering therapy is far more compelling for secondary versus primary
prevention.
A. True
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B. False
The correct answer is: True.
Therapeutic Lifestyle Changes (TLC)
Therapy with lipid-altering agents should be a component of multiple risk-factor intervention in
individuals at increased risk for atherosclerotic vascular disease due to hypercholesterolemia.
Therapeutic lifestyle changes should be initiated at LDL levels:
•
100 mg/dL for CHD or CHD risk equivalents
•
130 mg/dL for 2+ risk factors
•
160 mg/dL for 0–1 risk factor
Lipid-altering agents should be used in addition to an appropriate diet (including restriction of
saturated fat and cholesterol) and when the response to diet and other non-pharmacological
measures has been inadequate.
(Expert Panel on Detection Evaluation, and Treatment of High Blood Cholesterol in Adults, 2001)
TLC includes weight loss, exercise, smoking cessation and nutrition.
NCEP ATP III: Dietary Modification
The National Cholesterol Education Program (NCEP) expert panel on the Detection, Evaluation and
Treatment of High Blood Cholesterol in Adults recommends the above nutritional composition as part
of the Adult Treatment Panel (ATP) III Therapeutic Lifestyle Changes (TLC) diet.
2013 ACC/AHA Expert Panel Report
In November 2013, a multi-agency, evidenced-based panel published new recommendations online
intended to update the Adult Treatment Panel (ATP-III) guidelines.
The expert panel recommendations arose from careful consideration of an extensive body of higher
quality evidence derived from randomized controlled trials and systematic reviews and meta-analyses
of randomized, controlled trials.
Four groups of individuals were identified for whom sufficient evidence demonstrates a reduction in
atherosclerotic cardiovascular disease (ASCVD) events (including coronary heart disease,
cardiovascular deaths, and fatal and nonfatal strokes) with a good margin of safety from statin
therapy.
(Stone et al., 2013)
Indications for Statin Therapy
Four groups of individuals who benefit from statins:
1. Individuals with clinical ASCVD (acute coronary syndromes, or a history of MI, stable or unstable
angina, coronary or other arterial revascularization, stroke, TIA, or peripheral arterial disease
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presumed to be of atherosclerotic origin) without New York Heart Association (NYHA) class II-IV
heart failure or receiving hemodialysis.
2. Individuals with primary elevations of LDL ≥190 mg/dL.
3. Individuals 40-75 years of age with diabetes, and LDL 70-189 mg/dL without clinical ASCVD.
4. Individuals without clinical ASCVD or diabetes, who are 40-75 years of age with LDL 70-189
mg/dL and have an estimated 10-year ASCVD risk of 7.5% or higher.
(Stone et al., 2013)
Lifestyle Modification Recommendations
Lifestyle modification, such as adhering to a heart healthy diet, regular exercise habits, avoidance of
tobacco products and maintenance of a healthy weight, remains a critical component of health
promotion and ASCVD risk reduction.
This lifestyle modification is recommended both prior to and in conjunction with the use of cholesterollowering drug therapies.
Statin drugs are generally preferred over other lipid-lowering therapies:
•
There is no evidence to support continued use of specific LDL and/or non–HDL treatment targets.
•
The appropriate intensity of statin therapy should be used to reduce risk in those most likely to
benefit.
•
Lipid-lowering therapies that are not statins (e.g. niacin, fibric acid drugs, etc.), whether used
alone, or in combination with statins, do not provide acceptable ASCVD risk reduction benefits
compared to their potential for adverse effects in the routine prevention of ASCVD.
(Stone et al., 2013)
Other Factors Used To Guide Therapy
For individuals not included in the four statin benefit groups and those whose 10-year risk is <7.5%,
other factors should be used to guide therapy. These other factors include:
•
Family history of premature ASCVD
•
LDL >160 mg/dL
•
High-sensitivity C-reactive protein ≥2 mg/dL
•
Coronary calcium score ≥300 Agatston units
•
≥75th percentile for age, sex, ethnicity
•
Ankle-brachial index <0.9
•
Elevated lifetime risk of ASCVD may be used to enhance the treatment decision making
(Stone et al., 2013)
Statin Therapy Guidelines
High-intensity statin therapy is defined as a daily dose that lowers LDL by ≥50%.
Moderate-intensity statins would lower LDL by 30% to <50%.
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All patients with known atherosclerotic cardiovascular disease (ASCVD) who are age ≤75 years, as
well as patients >75 years, should receive high-intensity statin therapy; or if not a candidate for highintensity, should receive moderate-intensity statin therapy.
(Stone et al., 2013)
Statin Therapy Guidelines
Those with an LDL ≥190 mg/dL should receive high-intensity or moderate-intensity statin therapy (if
not a candidate for the former).
Addition of other cholesterol-lowering agents can be considered to further lower LDL.
Diabetics with a 10-year ASCVD ≥7.5% should receive high-intensity statins and <7.5% moderateintensity statin therapy.
Persons 40-75 years with a ≥7.5% 10-year ASCVD risk should receive moderate- to high-intensity
statin therapy.
(Stone et al., 2013)
2013 ACC/AHA Expert Panel Report
The new guidelines refute the Adult Treatment Panel (ATP-III) report in several ways, based on
rigorous review of clinical trials. The new guidelines call into question the use of specific lipoprotein
targets, the notion that the lowest LDL targets are best. The new guideline also challenges the idea of
treating to level of ASCVD risk, and based upon lifetime risk of ASCVD.
The guideline emphasizes a patient-centered approach to primary prevention of ASCVD by
calculating patient risk, determining the risk reduction benefit, adverse effects, potential for
interactions, along with patient preferences all being considered before statins are begun.
The NHLBI publishes an online tool to calculate the 10-year ASCVD risk designed for adults aged 20
and older who do not have heart disease or diabetes: http://cvdrisk.nhlbi.nih.gov/.
(Stone et al., 2013)
Limitations of Guidelines
It’s important to emphasize that the guidelines, while extensive in scope, are not intended to
represent a comprehensive approach to dyslipidemia.
For example, the report states that there is insufficient evidence to support the routine use of nonstatin drugs in combination with statins to further reduce ASCVD events.
(Stone et al., 2013)
The guideline only focuses on treatments proven to reduce ASCVD.
Test Yourself
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Non-statin drugs, such as niacin and fibric acid drugs, provide acceptable ASCVD risk reduction
benefits as compared to statins.
A. True
B. False
The correct answer is: False.
Trials Published Since ATP III
Since the Adult Treatment Panel (ATP-III), several major clinical end point trials of statin therapy have
been published, such as the Heart Protection Study, PROSPER, PROVE IT, CARDS, MIRACL,
REVERSAL, JUPITER and TNT.
These newer studies indicate that more intensive LDL–lowering therapy provides a greater benefit
than less intensive LDL-lowering therapy.
These trials form the basis for recommending that reducing LDL substantially below 100 mg/dL
provides additional benefit, especially for secondary prevention in high risk patients.
(Heart Protection Study, 2002 – Sever et al., 2003)
Results from these trials confirm the benefit and safety of statins, particularly among high-risk
patients.
Heart Protection Study
A prospective, randomized study of 20,536 adults living in the United Kingdom (aged 40 to 80 years)
who were at high risk for a CVD event, such as coronary disease, other occlusive arterial disease, or
diabetes were studied in the Heart Protection Study in 2002.
In this study, patients were randomly allocated to 40 mg simvastatin daily or a placebo. The results
were as follows:
•
In patients allocated to simvastatin, all-cause mortality was significantly reduced by 13%
(p=0.0003)
•
Major vascular events were reduced by 24%, coronary death rate by 18%, nonfatal myocardial
infarction + coronary death by 27%, nonfatal or fatal stroke by 25%, and cardiovascular
revascularization by 24%
The investigators concluded that, in general, cholesterol lowering with statin therapy is efficacious in
patients with diabetes, including those without manifest CHD and those with relatively low LDL levels.
(Heart Protection Study, 2002)
The ASCOT Study
A randomized, prospective study was conducted of 19,342 hypertensive patients, 40 to 79 years old
and having at least 3 other cardiovascular risk factors, who were randomized to 1 of 2
antihypertensive regimens. Among these subjects, 10,305 were in addition randomly assigned
atorvastatin 10 mg or placebo.
The study was planned for a follow-up of an average of 5 years but was stopped after a median
follow-up of 3.3 years. At that time, 100 primary events had occurred in the atorvastatin group,
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compared with 154 events in the placebo group.
In the atorvastatin group, the incidence of fatal and nonfatal stroke was reduced by 27% (P=0.024),
total cardiovascular events by 21% (p=0.0005), and total coronary events by 29% (p=0.0005).
There was a non-significant trend toward a reduction in total mortality in the atorvastatin group (13%;
p=0.16).
The authors indicated that LDL lowering with atorvastatin therapy has considerable potential to
reduce risk for CVD in primary prevention in patients with multiple CVD risk factors.
(Sever et al., 2003)
Most LDL Reduction Occurs at Lower Doses of Statins
Test Yourself
A doubling of the dose of any given statin will result in an approximate 50% decrease in LDL.
A. True
B. False
The correct answer is: False.
Possible Reasons LDL Treatment Goals Unmet
Patients are not universally achieving National Cholesterol Education Program (NCEP) LDL goal on
current therapy. Some possible reasons include the following:
•
Lack of treatment initiation, primarily viewed as “outpatient therapy” only
•
Lack of medication adherence or lack of prescription coverage
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•
Lack of adequate titration
There are also several limitations of current therapy, including:
•
Statins: Inter-patient variability, liver and muscle toxicity
•
Fibric-acid derivatives: Possible prothrombotic effects (gemfibrozil)
•
Nicotinic acid: Poorly tolerated
•
Resins and bile acid sequestrants: Poor compliance due to poor tolerability
Adherence Curves for Statins in 3 Cohorts
Drugs Affecting Lipoprotein Metabolism
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(Tsuyuki et al., 2001; Expert Panel, 2001)
HMG-Co-A Reductase Inhibitors
Considered the best-tolerated and most potent LDL-lowering drugs.
All HMG-Co-A Reductase inhibitors (statins) can be given once daily.
Adverse drug reactions among statins are comparable and include headaches, GI effects, myalgias,
myopathy, increased LFT and CPK.
All statins are category X in pregnancy.
Both primary and secondary prevention studies have been published, multiple outcome and mortality
studies.
Atorvastatin and rosuvastatin generally reduces LDL most:
•
TC 29-45%, LDL 39-60%, HDL 5-10% inc, TG 19-35%
•
Rosuvastatin produces 7.7% - 9.6% increases in HDL
•
Atorvastatin produces 20% - 28.2% decrease in TG, slightly better than others
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(Tsuyuki et al., 2001; Expert Panel, 2001 & Lloyd-Jones et al., 2010)
HMG-Co-A Reductase Inhibitors
The most lipophilic statins (having the ability to dissolve in lipids) are simvastatin, lovastatin and
atorvastatin and pitavastatin.
The least lipophilic statins are rosuvastatin, pravastatin and fluvastatin.
The statins least affected by renal function are atorvastatin and fluvastatin.
The time of dose administration is most relevant for pravastatin, simvastatin and fluvastatin and
should be given at HS.
(Tsuyuki et al., 2001; Expert Panel, 2001 & Lloyd-Jones et al., 2010)
HMG-Co-A Reductase Inhibitors
The time of dose is less relevant for longer half-life drugs, such as atorvastatin, rosuvastatin and
pitavastatin.
The statin that are CYP3A4 substrates are atorvastatin, simvastatin and lovastatin.
The statins that are CYP2C9 substrates are rosuvastatin and fluvastatin.
The statins that are not substrates for CYP450 are pravastatin and pitavastatin.
(Tsuyuki et al., 2001; Expert Panel, 2001 & Lloyd-Jones et al., 2010)
Commercially Available Statins
Natural Statins
Lovastatin (Mevacor®) 20-80mg daily
Pravastatin (Pravachol®) 20-40mg daily
Simvastatin (Zocor®) 20-80mg daily
Synthetic Statins
Fluvastatin (Lescol®) 20-80mg daily
Atorvastatin (Lipitor®) 10-80mg daily
Rosuvastatin (Crestor®) 5-20mg daily
Pitavastatin (Livalo®) 1-4mg daily
Combination Products
Lovastatin + Niacin (Advicor®) [SR niactin + lovastatin]
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Simvastatin + Niacin (Simcor®) [SR niacin + simvastatin]
Atorvastatin + Amlodipine (Caduet®)
Simvastatin + Ezetimibe (Vytorin®)
Micromedex, 2013 & Lexi-Comp, 2013
HMG-Co-A Reductase Inhibitors: Dose-Dependent Lowering of LDL
Drug
Doses/Percentage of LDL Lowered
10mg - 38%
20mg - 46%
Atorvastatin
10mg - 28%
20mg - 35%
Simvastatin
5mg - 42%
10mg - 50%
Rosuvastatin
10mg - 19%
20mg - 24%
Pravastatin
20mg - 17%
40mg - 23%
Fluvastatin
20mg - 29%
40mg - 32%
Lovastatin
Simvastatin + Exetimible at maximum doses (10/80) = 47-59%
40mg - 48%
40mg - 41%
20mg - 52%
40mg - 34%
80mg - 36%
80mg - 48%
(Ballantyne et al., 2005)
HMG-Co-A Reductase Inhibitors: Pleiotropic Effects
Statins have beneficial effects within the vasculature that appear to be independent of their
lipoprotein-lowering effects. These actions are called pleiotropic effects and include the following:
•
Antiproliferative effects on vascular smooth muscle cells
•
Restoration of endothelial activity
•
Antithrombotic effects
•
Antioxidant effects
•
Anti-inflammatory effects
•
Decreases in C-reactive protein and other markers of vascular inflammation
(Liao & Lauf, 2005)
Myopathy Associated with Statin Therapy: NHLBI Advisory
Myalgia is characterized by muscle aches, soreness, or weakness.
Myopathy is a more general term referring to any disease of muscles, but often characterized by
myalgia accompanied by CK levels > 10,000 U/L (myositis is a more accurate term).
Rhabdomyolysis is an acute, potentially fatal disease of skeletal muscle that entails destruction of
skeletal muscle as evidenced by myoglobinemia and myoglobinuria (e.g. muscle sx plus renal
involvement).
Risk factors:
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•
Combination lipid-lowering therapy
•
Renal failure
•
Drug-drug interactions
Statins: Myalgia/Myopathy Syndrome
Rhabdomyolysis (the breakdown of skeletal muscle tissue), with or without acute renal failure
secondary to myoglobinuria, has been reported rarely.
With any statin, tell patients to promptly report muscle pain, tenderness, or weakness.
Discontinue drug if myopathy is suspected, if CPK levels rise markedly, or if the patient has risk
factors for rhabdomyolysis.
Monitor patients for any unexplained muscle pain, tenderness, or weakness, particularly during the
initial months of therapy and during any periods of upward dosage titration of either drug.
Other accompanying signs and symptoms may include fever, malaise and darkened urine.
(Pasternak, 2005)
Reported Incidence of Muscle Toxicity
The incidence of mylagia with a statin is 1.2-3.5%, in general, versus 1.0-2.9% with placebo.
The incidence of myopathy with a statin is 0.1-0.5% in general with statin monotherapy in low-risk
patients.
The incidence of rhabdomyolysis is <0.1% with statin monotherapy.
The incidence of fatal rhabdomyolysis is 0.15 deaths per 1 million statin prescriptions.
Statin-induced hepatoxicity is rare; check AST and ALT at baseline, after 12 weeks, then
“periodically” (e.g. every 2 years), unless a patient is symptomatic.
(Pasternak, 2005)
Note! The risk for muscle toxicity is multifactorial.
Mechanism of Myopathy
Statins lead to inhibited synthesis of cholesterol in myocytes. In theory, this could lead to ubiquinone
(an essential intracellular energy component) deficiency in muscle cell mitochondria, disturbing
normal cellular respiration.
No clinical study has yet provided support for the hypothesis of diminished energy generation
in muscle cells during statin therapy.
Intracellular depletion of metabolic intermediates is the leading, but unproven hypothesis.
The development of myopathy is likely to be multi-factorial, including a genetic predisposition, CYPrelated factors, the statin may unmask mitochodrial myopathy.
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(Pasternak, 2005)
Should Coenzyme Q10 be Added to Statins?
Co-Q10 is believed to be crucial for mitochondrial function and the provision of energy for cellular
processes.
Statins inhibit HMG-CoA which decreases the production of mevalonate, a precursor of both
cholesterol and coenzyme Q10.
There is speculation that a reduction in Co-Q10 concentrations may promote the myopathies that
have been associated with statin treatment as a result of mitochondrial damage.
Studies have demonstrated a reduction in circulating Co-Q10 concentrations with statins, but it is
unclear whether tissue levels of Co-Q10 are significantly affected.
Co-Q10 supplementation has been shown to reverse statin-induced decreases in circulating Co-Q10,
although the effect of supplementation on tissue levels and any resulting clinical benefit has not been
adequately assessed.
While no major safety concerns exist, there is little evidence to support its routine use for preventing
statin-induced muscle toxicity.
(Nawarskas, 2005)
Who is at Risk for Statin-Induced Muscle Toxicity?
The following groups of patients have been identified at risk for statin-induced muscle toxicity:
•
Patients with underlying renal impairment, elderly, those with hypothyroidism and hepatic
dysfunction
•
Patients with disorders that precipitate acute renal failure (ARF), such as sepsis, profound
dehydration and cardiogenic shock
•
Patients on higher doses of statins, especially if combined with gemfibrozil or niacin
•
Co-administration of a CYP450-3A4 substrate (atorvastatin, simvastatin and lovastatin) with a
known inhibitor, such as:
•
Azole antifungals
•
Erythromycin
•
Nefazodone
•
Grapefruit juice
•
CCBs
•
Cyclosporine
•
Tacrolimus
•
Several SSRIs
•
Tamoxifen
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(Pasternak et al., 2002 & Nawarskas, 2005)
Test Yourself
An elderly patient on combination lipid-lowering therapy is at risk for statin-induced muscle toxicity.
A. True
B. False
The correct answer is: True.
Hepatic Metabolism of HMG-CoA Reductase Inhibitors
HMG-CoA
CYP450 Substrate
Simvastatin
3A4
Lovastatin
3A4
Pravastatin
Pitavastin
Atorvastatin
No
Rosuvastatin
2C9
Fluvastatin
2C9
3A4
(Micromedex, 2013 & Lexi-Comp, 2013)
CYP 3A4 Drug Interactions
Important inhibitors of CYP-3A4 include the following:
• Cimetidine, fluoxetine, ketoconazole, sertraline, fluvoxamine, clarithromycin, diltiazem,
erythromycin, fluconazole, metronidazole, omeprazole, verapamil, nefazodone, grapefruit juice,
cyclosporine, itraconazole
Important inducers of CYP-3A4 include the following:
• Phenobarbital, carbamazepine, phenytoin, dexamethasone, INH, rifampin
(Micromedex, 2013 & Lexi-Comp, 2013)
Effect of Co-Administration of Food on Statin Bioavailability
Increase:
•
Lovastatin - Up to 50% increase
No significant effect:
•
Simvastatin
•
Rosuvastatin
•
Pitavastatin
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Decrease:
•
Pravastatin - Up to 30% decrease
•
Fluvastatin - ~20% decrease
•
Atorvastatin - ~13%decrease
(Micromedex, 2013 & Lexi-Comp, 2013)
Complimentary Mechanisms between Ezetimibe and Statins
The effects of ezetimibe, either alone or in addition to a statin, on long-term cardiovascular
morbidity or mortality have not been established.
When ezetimibe is used in conjunction with a statin, it reduces the delivery of cholesterol to the liver,
and statins reduce cholesterol synthesis in the liver.
The distinct mechanism of ezetimibe is complementary to that of statins.
Ezetimibe monotherapy is not generally recommended as a first-line treatment of dyslipidemia.
(Micromedex, 2013 & Lexi-Comp, 2013)
Nurse-to-Patient Education
APRNs should:
•
Educate patients on risks of dyslipidemia.
•
Counsel patients on therapeutic lifestyle modification.
•
Promote screening for hyperlipidemia.
•
Monitor and screen patients for adverse reactions and interactions.
•
Use adherence aids and give feedback to prescriber when patients are not adherent.
•
Recommend fasting lipid profiles in high risk patients.
•
Consider dietary advice and referral to a registered dietitian.
•
Optimize lipid-lowering drug dosing and consider the effect of drug and/or food interactions.
•
Counsel women of child-bearing potential about statins.
•
Refer patients to pharmaceutical assistance programs if patients do not have prescription
coverage www.pparx.org.
Conclusion
By educating patients on the management of dyslipidemia, APRNs can reduce a major risk factor for
cardiovascular disease and improve the quality of life for patients.
References
Wells BG. Chapter 28. Dyslipidemia. In: Wells BG, ed. Pharmacotherapy: A Pathophysiologic
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Approach. 8th ed. New York: McGraw-Hill; 2011. http://0www.accesspharmacy.com.polar.onu.edu/content.aspx?aID=7974214. Accessed November 7, 2013.
Carroll MD, Kit BK, Lacher DA, Yoon SS. Total and high-density lipoprotein cholesterol in adults:
National Health and Nutrition Examination Survey, 2011–2012. NCHS data brief, no 132. Hyattsville,
MD: National Center for Health Statistics. 2013.
Expert Panel on Detection Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive
summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on
Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III).
JAMA 2001;285:2486–2497.
Stone NJ, Robinson J, Lichtenstein AH, Bairey Merz CN, Lloyd-Jones DM, Blum CB, et al. 2013
ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular
Risk in Adults, Journal of the American College of Cardiology (2013), doi:10.1016/j.jacc.2013.11.002.
Grundy SM, Cleeman JI, Merz CN, et al. Implications of recent clinical trials for the National
Cholesterol Education Program Adult Treatment Panel III Guidelines. Journal of the American
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