Management Strategies of Dyslipidemia in the Elderly: 2005
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Management Strategies of Dyslipidemia in the Elderly: 2005
Tarek Helmy, MD; Amar D. Patel, MD; Fadi Alameddine, MD; Nanette K.
Wenger, MD, FACC, FAHA
Medscape General Medicine. 2005;7(4):8. ©2005 Medscape
Posted 10/10/2005
Abstract and Introduction
Abstract
During the past 3 years, the treatment of dyslipidemia has evolved
significantly. The impact of recent trial data on management strategies in
older patients is especially important, because the elderly segment of the US
population continues to grow. Several clinical trials have been completed
since the publication of the National Cholesterol Education Program (NCEP)
Adult Treatment Panel III guidelines were published in 2001. Recent trial data
strongly support the use of lipid-lowering therapy in the elderly population.
Although therapeutic lifestyle changes remain highly important,
supplementation with lipid-lowering therapy has been shown to reduce the risk
of cardiovascular events in both primary and secondary prevention models.
Compelling data noted from recent clinical trials have prompted the NCEP to
publish an updated report that addresses the significant interim developments.
Introduction
Given that several epidemiologic studies have identified the elderly
population as having a high risk for cardiovascular events, risk-factor
modification plays an important role in an attempt to reduce adverse
cardiovascular events. Management of dyslipidemia in the elderly is of
particular clinical relevance, as the population proportion of the aged is
becoming greater over time. Even though dyslipidemia is established as one of
the major risk factors for the development of coronary artery disease (CAD) in
the elderly, most of these data have been derived from large clinical trials
that are mainly comprised of middle-aged patients. However, the association
between dyslipidemia and CAD holds true for patients over 65 years of age.
Large population-based studies, such as the Established Populations for
Epidemiology Studies in the Elderly (EPESE), revealed that an elevated total
cholesterol level and low high-density lipoprotein cholesterol (HDL-C) level
are associated with increased risk of cardiovascular mortality, especially in
men.[1,2] Conversely, lower cholesterol levels (as seen in vegetarians) were
associated with a lower incidence of CAD and cardiovascular death in patients
between the ages of 75 and 84 when compared with nonvegetarians with higher
cholesterol levels.[3]
Despite a growing body of evidence regarding the benefits of aggressive
reduction of cholesterol levels, older patients with either documented
dyslipidemia or significant risk factors for the development of CAD are often
underdiagnosed or undertreated. Data from a study conducted in Canada
demonstrated that among hospitalized patients at high risk for cardiovascular
events, risk-factor assessment and modification were suboptimal, particularly
for women and elderly patients.[4] This may be the result of a paucity of
evidence regarding the impact of treatment on delaying the progression of
atherosclerotic disease in response to screening-guided therapy, concerns of
the increased likelihood of adverse events or drug interactions, or doubts
regarding the cost-effectiveness of lipid-lowering drug therapy in the elderly
population. The National Cholesterol Education Program (NCEP) Adult Treatment
Panel (ATP) III report recommends that all adults with blood total cholesterol
values above 200 mg/dL be evaluated and that those with elevated low-density
lipoprotein cholesterol (LDL-C) levels be treated.[5] Furthermore, no upper
age limit should be defined for lipid-lowering interventions in patients with
CAD or at increased risk for CAD.[5] Based on the NCEP guidelines, about one
third of elderly men and one half of elderly women have elevated cholesterol
levels warranting intervention.[6] ATP III expands the indications for
intensive cholesterol-lowering therapy in clinical practice. Elevated
triglyceride (TG) levels are also considered to be an independent risk factor
for developing CAD. Although this was initially difficult to demonstrate in
individual studies (mainly due to multiple variables and confounding risk
factors),[7] a recent meta-analysis validated the importance of TG as a
cardiovascular risk factor.[8,9] As such, the ATP III guidelines now include
TG level reduction as a secondary target after LDL-C reduction has been
achieved.
Patient Evaluation
Unfortunately, outcome data regarding lipid lowering in the elderly are
relatively limited, and the ATP III recommendations for older patients are
generally extrapolated from data derived from younger populations. However,
emerging clinical trial data from studies, such as the Heart Protection Study
(HPS),[10] Anglo-Scandinavian Cardiac Outcomes Trial - Lipid Lowering Arm
(ASCOT-LLA),[11] and Prospective Study of Pravastatin in the Elderly at Risk
(PROSPER),[12] provide valuable insight regarding the treatment of
dyslipidemia in the elderly.
The first step in selection of LDL-C lowering therapy is to assess the
risk status of the individual. Risk determinants, in addition to LDL-C levels,
include the presence of CAD (or coronary heart disease [CHD]), other clinical
forms of atherosclerotic disease, cigarette smoking, hypertension, age ( men >
45 years, women > 55 years), low levels of HDL-C (< 40 mg/dL), and family
history of premature coronary disease (CAD in a first-degree male relative <
55 years or a first-degree female relative < 65 years). Based on these risk
factors, ATP III outlines 3 risk categories that define the goals and
modalities of LDL-C lowering therapy (Table 1). CHD refers to myocardial
infarction (MI), angina, coronary revascularization procedures, or clinically
evident myocardial ischemia. CHD risk equivalents include clinical forms of
atherosclerotic disease other than CAD (peripheral arterial disease, abdominal
aortic aneurysm, and symptomatic carotid artery disease), diabetes mellitus,
and multiple risk factors (2 or more) that confer a 10-year risk for CHD >
20%.
The NCEP has published a report that reflects the additional clinical
trial data that have been published since 2001.[13] Of significance, a new
treatment goal that was addressed, as a result of the data from the HPS and
Pravastain or Atorvastatin and Infection Therapy (PROVE-IT)[14] clinical
trials, was the potential importance of reducing the LDL-C level to 70 mg/dL
in very high risk patients. Individuals who are considered at very high risk
are those with known cardiovascular disease plus (1) multiple major risk
factors (especially diabetes mellitus), (2) severely and poorly controlled
risk factors (especially continued tobacco use), (3) multiple risk factors for
the metabolic syndrome, and (4) patients with acute coronary syndromes.
Further data to support lower LDL-C goals are provided by the recently
published Treating New Targets (TNT) study.[15] For now, LDL-C reduction to <
70 mg/dL remains a therapeutic option on the basis of clinical trial evidence,
whereas a goal LDL-C < 100 mg/dL remains their strong recommendation.
Treatment
Nonpharmacologic Interventions
Dyslipidemia can be significantly improved by therapeutic lifestyle
changes, such as dietary modification, physical activity, and weight
reduction. The potential for diet to prevent cardiovascular disease is often
underappreciated by patients. Furthermore, changing ingrained dietary habits
is not usually an easy task for most patients. Diet favorably alters the
lipid/lipoprotein profile and may allow the use of lower doses of
lipid-lowering agents, thus reducing the potential for adverse effects. ATP
III recommends reduced intake of saturated fatty acids (< 7% of total
calories) with the remainder of total fats from polyunsaturated and
monounsaturated fatty acids (25% to 35% of total calories), and intake of less
than 200 mg cholesterol/day. The addition of plant stanols/sterols (2 g/day)
and soluble fiber (10-15 g/day) can further reduce LDL-C by approximately 10%.
Carbohydrates should be limited to 60% of the total daily caloric intake. The
Lyon Diet Heart Study is a secondary prevention trial that randomized 605
patients to a Mediterranean-type or a Western-type diet.[16] Despite a similar
coronary risk profile between the groups, there was an approximate 50% to 70%
relative risk reduction of cardiovascular events (death, MI, stroke, angina,
congestive heart failure, and hospitalization) in favor of the
Mediterranean-type diet group over a mean follow-up duration of 46 months.
The benefits of the Mediterranean diet were also shown in a prospective
study of 22,043 subjects with an age range of 20-86 years. An extensive,
validated, food frequency questionnaire was completed at baseline, and
subjects were followed for a median of 44 months. Calculation of dietary
intake included 14 food groups: potatoes, vegetables, legumes, fruits and
nuts, dairy products, cereals, meat, fish, eggs, monounsaturated lipids
(mainly olive oil), polyunsaturated lipids (vegetable seed oil), saturated
lipids and margarines, sugar and sweets, and nonalcoholic beverages.
Evaluation of occupational and leisure-time physical activity was also
included. Adherence to the Mediterranean diet was associated with reduced
mortality, with a strong association with cardiovascular mortality.[17]
The HALE project was another study evaluating the effects of a
Mediterranean diet in the elderly. This included 1507 healthy men and 832
women aged 70-90 years in 11 European countries who were followed for 10
years. A Mediterranean diet, moderate alcohol consumption, moderate-to-high
physical activity levels, and nonsmoking were associated with lower mortality
rates, including CHD, cardiovascular disease, cancer, and other causes of
mortality.[18]
A study by Lemaitre and colleagues[19] investigated the effects of
plasma phospholipid concentrations of n-3 polyunsaturated fatty acids
(docosahexanenoic acid [DHA]), eicosapentaenoic acid (EPA), and
alpha-linolenic acid on ischemic heart disease in elderly patients (age > 65).
DHA and EPA are commonly found in fatty fish, whereas alpha-linolenic acid is
found in vegetable oils. This was a case-control study nested in the
prospective trial of cardiovascular risk factors and outcomes (the
Cardiovascular Health Study). Subjects were included if they were free of
ischemic heart disease and stroke at baseline, and experienced an MI (fatal or
nonfatal) during follow-up. Cases were matched to subjects with the same age,
sex, clinical site, and follow-up period in a random fashion. Higher dietary
intake of DHA, EPA, and possibly alpha-linolenic acid was associated with a
decrease in the incidence of nonfatal ischemic events, when the analysis was
adjusted for other coronary risk factors.[19]
Physical inactivity is a major risk factor for CAD.[20] Physical
exercise and weight reduction are important elements of therapeutic lifestyle
changes, and have a favorable impact on the lipid profile, blood pressure
levels, and improve insulin sensitivity. Physical exercise has been reported
to reduce the risk of developing CAD by as much as 40%, independent of
standard risk-factor modifications.[20] Most patients underestimate their
dietary intake and overestimate their level of physical activity and exercise.
Scheduled, regular exercise promotes the energy expenditure that is necessary
to maintain a desirable body weight. This is especially important because the
lifestyles of an increasing percentage of the US population are becoming more
sedentary.
Pharmacologic Management
Several agents are available for lipid lowering, such as
hydroxyl-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors ("statins"),
nicotinic acid, fibrates, bile acid sequestrants, and intestinal absorption
inhibitors, such as ezetimibe. These agents have specific and different
effects on the lipid profile. Fibrates lower TG by 20% to 50%, lower LDL-C by
5% to 20%, and raise HDL-C by 10% to 20%. Nicotinic acid lowers LDL-C by 5% to
25%, lowers TG by 20% to 50%, and raises HDL-C by 15% to 35%. Bile acid
sequestrants lower LDL-C by 15% to 30%, raise HDL-C by 3% to 5%, and have no
consistent predictable effect on TG levels, thus warranting caution in
patients with mixed lipid abnormalities with hypertriglyceridemia. Statins
lower LDL-C by as much as 50% with some agents, raise HDL-C by 5% to 15%, and
lower TG by approximately 30%. Statins also may have "pleiotropic effects"
that are independent of lipid lowering. They include vasodilator (through
nitric oxide release) and anti-inflammatory effects on vascular endothelial
cells, as well as antiproliferative and antimigratory effects on vascular
smooth muscle cells. Statins also reduce tissue factor release, inhibit
thromboxane activity (leading to inhibition of platelet activation), modulate
the recruitment of inflammatory cells, and reduce expression of adhesion
molecules in the vascular wall.[21]
Statins are the drug of choice for patients with elevated LDL-C levels.
Clinical trials have unequivocally demonstrated that treatment of dyslipidemia
with statins reduces cardiovascular events both in patients at high risk for
CAD (primary prevention)[10,11,22,23] and in patients with documented CAD
(secondary prevention)[10,12,14,15, 24-26] (Table 2). Unfortunately, large
multicenter, clinical trials, such as West of Scotland Coronary Prevention
Study (WOSCOPS),[22] excluded patients over age 65; the Scandinavian
Simvastatin Survival Study (4S)[26] excluded patients older than 70; and the
Cholesterol and Recurrent Events (CARE)[24] and Long-Term Intervention with
Pravastatin in Ischaemic Disease (LIPID)[25] trials excluded patients over the
age of 75. Although outcomes data are relatively limited in the elderly, some
studies included a sizable elderly cohort. In the 4S trial,[26,27] patients 65
years and older derived more benefit from simvastatin than patients ? 65 years
(Table 3). A significant reduction in all-cause mortality was evident at 18
months, whereas coronary event rates (coronary death, nonfatal MI,
resuscitated cardiac arrest, and silent MI) decreased significantly after 6
months of statin therapy. The CARE trial enrolled 4159 patients (1283 patients
aged 65-75) with a history of MI and a serum LDL-C ? 115 mg/dL.[24] After a
5-year mean follow-up, the incidence of major coronary events (fatal MI,
ischemic cardiomyopathy, and sudden death) was reduced by 27% in patients aged
60-75 compared with a 20% reduction in patients younger than age 60. The LIPID
trial had similar findings showing that for every 1000 patients treated with
pravastatin for 6 years, 133 coronary events were prevented in the 65-75 age
group.[25]
The HPS, the largest statin therapy trial conducted to date, randomized
20,563 patients aged 40-80 years (10,697 patients ? 65 years) with coronary
disease, other occlusive arterial disease, or diabetes to either 40 mg of
simvastatin or placebo during a scheduled 5-year treatment period.[10]
All-cause mortality was significantly reduced in the simvastatin group, mainly
driven by an 18% relative risk reduction in the coronary death rate (MI,
ischemic cardiomyopathy, and sudden death) (5.7% vs 6.9%; P = .0005). There
was a trend toward a reduction in other vascular deaths (.9% vs 2.2%; P = .07)
and an insignificant reduction in nonvascular deaths (5.3% vs 5.6%; P = .4).
Furthermore, there was a 25% reduction in the incidence of nonfatal MI or
coronary death (8.7% vs 1.8%; P < .0001), stroke (44.3% vs 5.7%; P < .0001),
and coronary or noncoronary revascularization (9.1% vs 1.7%; P < .0001). The
reduction in major vascular events was not significant during the first year,
but was highly significant during each subsequent year. The proportional
reduction in the event rate was similar and statistically significant when
predesigned subgroup analysis was performed by age (under or over 70 years at
study entry). There was also a 27% decrease in stroke incidence. The annual
excess risk of myopathy with this regimen was about .01%. There were no
significant adverse effects on cancer incidence or on hospitalizations for any
nonvascular cause. Statin therapy conferred a decrease in total and
cardiovascular mortality without an increase in noncardiovascular mortality.
This was true even in patients with baseline LDL-C ? 100 mg/dL in a post hoc
analysis. The safety profile was identical in both groups and no deterioration
in cognitive function was noted.
Another landmark study, PROSPER,[12] randomized an elderly cohort of men
and women aged 70-82 years with, or at risk of developing, vascular disease
(coronary, cerebral, or peripheral) to pravastatin (40 mg per day; n = 2891)
or placebo (n = 2913). Pravastatin lowered LDL-C concentrations by 34% and
demonstrated a 15% relative risk reduction in the composite primary end point
of coronary death, nonfatal MI, and fatal or nonfatal stroke over a mean
follow-up duration of 3.2 years (hazard ratio, .85; 95% confidence interval
[CI], .74-.97; P = .014). CHD death and nonfatal MI risk were also reduced
(hazard ratio, .81; 95% CI, .69-.94; P = .006). Stroke risk was unaffected
(hazard ratio, 1.03; 95% CI, .81-1.31; P = .8), but the hazard ratio for
transient ischemic attack was .75 (95% CI, .55-1.00; P = .051). The small
number of strokes in this study may explain the lack of statistical
significance observed. New cancer diagnoses were more frequent with
pravastatin than with placebo (hazard ratio, 1.25; 95% CI, 1.04-1.51; P =
..020). However, incorporation of this finding in a meta-analysis of all
pravastatin and all statin trials showed no overall increase in cancer risk.
Mortality from coronary disease fell by 24% (P = .043) in the pravastatin
group. Pravastatin had no significant effect on cognitive function or
disability. The study authors of PROSPER concluded that pravastatin similarly
reduces the risk of CAD in elderly patients as demonstrated in younger aged
populations. In addition, this study supported the well-documented safety
profile and tolerability of statin therapy. Statin drugs appear to have
similar efficacy and safety in nonelderly and elderly populations and should
be strongly considered for use in elderly patients.[28-30] A soon to be
completed study in elderly patients is the Study Assessing Goals in the
Elderly (SAGE), which is designed to compare the effects of atorvastatin 80 mg
with pravastatin 40 mg on myocardial ischemia, as assessed by Holter
monitoring.
New targets for LDL-C reduction, now an optional recommendation from the
NCEP-ATP III guidelines, are strongly supported by 2 recent studies. In
PROVE-IT, 4162 patients with an acute coronary syndrome were randomized to an
aggressive strategy of LDL-C reduction, with high-dose atorvastatin vs usual
therapy, with a moderate dose of pravastatin.[14] At 2-year follow-up, the
combined end point (time from randomization to death/MI/stroke/coronary
revascularization/unstable angina requiring hospitalization) was significantly
better in the aggressive therapy group (LDL-C 62 mg/dL) compared with the
usual therapy group (LDL-C 95 mg/dL). The recently published TNT trial was the
first randomized clinical trial to prospectively assess the efficacy and
safety of treating patients with stable CAD to LDL-C levels significantly
below 100 mg/dL.[15] The TNT trial compared the effects of a lower goal of
LDL-C reduction with high-dose (80 mg) atorvastatin to current LDL goal, with
low-dose (10 mg) atorvastatin, and included patients as old as 75 years. At
the end of a 5-year follow-up period, the mean LDL-C level in the high-dose
atorvastatin group was 77 mg/dL compared with 102 mg/dL in the lower dose
group. There was a significant (> 20%) reduction in the primary combined end
point of death, MI, and stroke in the lower LDL-C group.
In addition to trials focusing on the use of statin therapy, several
studies have also been conducted regarding the therapeutic efficacy of fibrate
therapy on secondary prevention. The Veterans Affairs High Density Lipoprotein
Cholesterol Intervention Trial (VA-HIT) study evaluated the use of gemfibrozil
in patients with low levels of HDL-C. In this trial, 2531 male patients with
documented CAD were randomized to gemfibrozil or placebo.[31] During a
follow-up period of 5 years, there was a 24% relative risk reduction in the
combined outcomes of CHD death, nonfatal MI, or stroke. At 1 year, HDL levels
were 6% higher and TG levels were 31% lower in the gemfibrozil group. Further
analysis of the data revealed that gemfibrozil therapy was cost-effective and
efficacious across a wide age range (55-75 years). Another study of post-MI
patients that included a large elderly cohort described a 28% reduction in
total mortality in patients treated with the lipid-lowering agents clofibrate
and nicotinic acid.[32]
A new class of lipid-lowering drugs is the cholesterol absorption
inhibitors. The first drug of this class, ezetimibe, was approved by the US
Food and Drug Administration (FDA) in November 2002. It interferes with the
absorption of dietary and biliary cholesterol at the intestinal brush border
without interfering with uptake of TGs.[33,34] It should be considered as an
adjunct to therapy in patients in whom LDL-C reduction is suboptimal, despite
maximal statin monotherapy. Ezetimibe can achieve as much as an additional 10%
to 15% reduction in the LDL-C level. To date, clinical outcomes data are
lacking for ezetimibe, but these trials are ongoing. Although ezetimibe has
been administered in the elderly,[35] its therapeutic efficacy has not been
specifically evaluated in this population subset.
Combination therapy is also now evolving in which agents targeting
different, but usually coexistent, disease processes are combined in a single
pill. Observational data have shown that coexistent risk factors, such as
hypertension and dyslipidemia, have multiplicative effects on the risk for
development of cardiovascular events.[36] The marked relative risk reduction
of adverse cardiovascular events in both the hypertension and lipid-lowering
arm of the ASCOT trial prompted a premature termination of both arms of this
study. Results from this study as well as the aggressive LDL-C lowering trials
have led to the emergence of combination preparations, including combined
classes of lipid-lowering agents (simvastatin/ezetimibe), and lipid-lowering
and antihypertensive agents (atorvastatin/amlodipine).
Conclusions and Future Directions
Reducing LDL-C has been shown to decrease cardiovascular events to 80
years of age, but studies are needed to explore the efficacy of lipid-lowering
therapy in individuals older than 80 years. The magnitude of delay in
progression of atherosclerotic disease in response to screening-guided therapy
has not been well delineated. The cost-effectiveness of lipid screening in the
elderly population, as well as the subgroups that would benefit most from such
screening, need to be further studied. Based on ongoing clinical trial data,
the guidelines may be modified to recommend that an LDL-C ? 70 mg/dL is the
target level for special high-risk populations. In the PROVE-IT study, a
subgroup analysis showed less benefit in patients over the age of 65 compared
with patients less than 65 years of age. The TNT trial excluded patients over
the age of 75. Hence, the applicability of these data to the elderly
population needs to be better defined. Optimal implementation of the current
guidelines and the use of available agents will ultimately depend on expanding
the knowledge base of healthcare providers, and may require far-reaching
educational programs that change the way that risk-factor management is viewed
by caregivers and patients alike.
Table 1. Categories of Risk and LDL-C Goals
Risk Category 0-1 Risk Factor 2+ Risk Factors
(10-Year Risk ? 20%) CHD orCHD Risk Equivalents
(10-Year Risk > 20%)
LDL goal (mg/dL) < 160 < 130
(Optional < 100) < 100
(Optional < 70)
LDL level at which to start TLC (mg/dL) ? 160 ? 130 ? 100
LDL level at which to consider drug therapy (mg/dL) ? 190
(160-189: LDL-C lowering drug optional) If 10-year risk is 10%
to 20%, ? 130
If 10-year risk is < 10%, ? 160 ? 130 (100-129: LDL-C lowering
drug optional)
CHD = coronary heart disease; LDL-C = low-density lipoprotein
cholesterol; TLC = therapeutic lifestyle changes
Table adapted from: 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
Table 2. Primary and Secondary Prevention Trials Involving Statin
Therapy
Primary Prevention Secondary Prevention
WOSCOPS[22] CARE[24]
AFCAPS/TexCAPS[23] LIPID[25]
HPS[10] HPS[10]
ASCOT-LLA[11] 4S[26]
PROSPER[12]
PROVE-IT[14]
TNT[15]
WOSCOPS = West of Scotland Coronary Prevention Study; AFCAPS/TexCAPS =
Air Force/Texas Coronary Atherosclerosis Prevention Study; HPS = Heart
Protection Study; ASCOT-LLA = Anglo-Scandinavian Cardiac Outcomes Trial --
Lipid Lowering Arm; CARE = Cholesterol and Recurrent Events; LIPID = Long-Term
Intervention with Pravastatin in Ischaemic Disease; 4S = Scandinavian
Simvastatin Survival Study; PROSPER = Prospective Study of Pravastatin in the
Elderly at Risk; PROVE-IT = Pravastain or Atorvastatin and Infection Therapy;
TNT = Treating to New Targets
Table 3. Effect of Simvastatin on Cardiovascular End Points by Patient
Age
End Point Reduction (%)
Age < 65 Reduction (%)
Age 65-70
All-cause mortality 28 34
CAD mortality 42 43
Major coronary events 34 34
Coronary revascularization 35 41
Nonfatal MI 33 33
Any atherosclerosis-related point 24 34
CAD = coronary artery disease; MI = myocardial infarction
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27.. Miettinen TA, Pyorala K, Olsson AG, et al.
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28.. Pacala JT, McBride PE, Gray SL. Management of older adults
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29.. Santinga JT, Rosman HS, Rubenfire M, et al. Efficacy and
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30.. Hulley SB, Newman TB. Cholesterol in the elderly. Is it
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31.. Rubins HB, Robins SJ, Collins D, et al. Gemfibrozil for the
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32.. Carlson LA, Rosenhamer G. Reduction of mortality in the
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treatment with clofibrate and nicotinic acid. Acta Med Scand.
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33.. Van Heek M, Farley C, Compton DS, Hoos L, Davis HR.
Ezetimibe selectively inhibits intestinal cholesterol absorption in rodents in
the presence and absence of exocrine pancreatic function. Br J Pharmacol.
2001;134:409-417. Abstract
34.. Van Heek M, France CF, Compton DS, et al. In vivo
metabolism-based discovery of a potent cholesterol absorption inhibitor,
SCH58235, in the rat and rhesus monkey through the identification of the
active metabolites of SCH48461. J Pharmacol Exp Ther. 1997;283:157-163.
Abstract
35.. Feldman T, Koren M, Insull W Jr, et al. Treatment of
high-risk patients with ezetimibe plus simvastatin co-administration versus
simvastatin alone to attain National Cholesterol Education Program Adult
Treatment Panel III low-density lipoprotein cholesterol goals. Am J Cardiol.
2004;93:1481-1486. Abstract
36.. Kannel WB. Importance of hypertension as a major risk
factor in cardiovascular disease. In: Bosch JGR, ed. Hypertension. New York:
McGraw-Hill; 1999:888-910.
Tarek Helmy, MD, Assistant Professor of Medicine and Cardiology, Grady
Memorial Hospital, Atlanta, Georgia. Email: thelmy@xxxxxxxxx
Amar D. Patel, MD, Cardiology Fellow, Division of Cardiology, Emory
University School of Medicine, Atlanta, Georgia
Fadi Alameddine, MD, Fellow, Interventional Cardiology, Division of
Cardiology, Department of Medicine, Emory University School of Medicine,
Atlanta, Georgia
Nanette K. Wenger, MD, FACC, FAHA, Chief of Cardiology, Grady Memorial
Hospital, Atlanta, Georgia; Professor of Medicine, Department of Medicine,
Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia
Disclosure: Tarek Helmy, MD, has disclosed no relevant financial
relationships.
Disclosure: Amar D. Patel, MD, has disclosed no relevant financial
relationships.
Disclosure: Fadi Alameddine, MD, has disclosed no relevant financial
relationships.
Disclosure: Nanette K. Wenger, MD, FACC, has disclosed that she has
received research grants/contracts from and is on the trial steering committee
for Eli Lilly, AstraZeneca, and Pfizer, and is a consultant for the Eli Lilly
Raloxifene Advisory Committee; Heart Disease in Women, MED-ED; Pfizer; the
Cardiology/Lipidology Advisory Board, Merck; Bristol-Myers Squibb; the
Ranolazine Advisory Board, CV Therapeutics; Sanofi-Aventis; Kos
Pharmaceuticals W.A.T.C.H. Program; the NitroMed Heart Failure Advisory Board;
Leadership Council for Improving Cardiovascular Care Executive Committee;
Schering-Plough; and the Coreg Post-MI Advisory Panel, GlaxoSmithKline. Dr.
Wenger has also disclosed that she is on the speaker's bureau (CME) for
Pfizer, Novartis, Merck, Bristol-Myers Squibb, Eli Lilly, and NitroMed.
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