Diagnůstico y Tratamiento
Fam Physician 2000 Jun 1;61(11):3371-82 [Texto
Choosing drug therapy for patients with hyperlipidemia.
Safeer RS, Lacivita CL
Division of Family Practice, George Washington University School of
Health Sciences, Washington, DC, USA.
Almost 13 million American adults require drug therapy to meet the
low-density lipoprotein goals set by the National Cholesterol Education
Program. Attempts to achieve these goals through diet and exercise are
often unsuccessful. Major studies in recent years have demonstrated that
statins decrease low-density
lipoprotein levels, coronary events and overall mortality. Statins are the
most commonly prescribed lipid-lowering agents because they are effective,
well tolerated and easy to administer. Niacin has beneficial effects on
all of the main lipid components, and new extended-release tablets have
fewer adverse effects. Fibrates remain the most effective agents in
lowering triglyceride levels and should be limited to this use. Bile acid
sequestrants are seldom prescribed because of their adverse
gastrointestinal effects and cumbersome administration.
Am J Cardiol 2000 Jun 22;85(12A):20E-3E
Population benefits of cholesterol reduction: epidemiology, economics,
Department of Community and Preventive Medicine, University of Rochester
School of Medicine, Rochester, New York 14642, USA.
Cardiovascular disease mortality-rate reductions have slowed in the United
States in the last decade, suggesting that additional strategies are
needed to reduce rates further. Population-wide cholesterol reduction is a
promising approach. Selection of a particular strategy is less an issue of
efficacy, which has been proven through numerous studies, than it is an
issue of epidemiology, economics, and ethics. These 3 imperatives
constitute the foundation of renewed efforts to reduce the US population's
cholesterol levels. Epidemiologic imperatives include risk reduction in
low-to-moderate risk individuals, who comprise approximately 30% of the
population and one third of incident cases of coronary disease. Any
cholesterol-lowering strategy must address the challenge of reducing the
incidence of coronary disease; to do otherwise will result in an
increasing prevalence of disease, with the attendant cost and disability
burdens. Economic imperatives include the extension of preventive coverage
to the low-to-moderate risk segment of the population, which currently is
not included in any risk-reduction programs. Although cholesterol
reduction with pharmacologic agents may not meet current standards for
cost-effectiveness, over-the-counter (OTC) agents are under the rubric of
individual, not societal, costs. Finally, current and proposed options for
nonprescription cholesterol-lowering drugs raise a number of ethical
issues such as beneficence, nonmaleficence, justice, and autonomy.
Population-wide cholesterol reduction must be a mainstay for any strategy
to reduce the burden of cardiovascular disease.
J Clin Endocrinol Metab 2000 Jun;85(6):2089-112
Hyperlipidemia: diagnostic and therapeutic perspectives.
Ballantyne CM, Grundy SM, Oberman A, Kreisberg RA, Havel RJ, Frost PH,
Department of Medicine, Baylor College of Medicine, Houston, Texas 77030,
Geriatrics 2000 May;55(5):22-8 [Texto
completo en formato PDF]
Hypercholesterolemia. Is lipid-lowering worthwhile for older patients?
VA Central California Health Care System, Fresno, USA.
Despite some indications to the contrary, evidence continues to accumulate
that controlling cholesterol levels with drug therapy in older persons is
a worthwhile goal. Older persons with hypercholesterolemia have an
elevated risk of coronary heart disease morbidity and mortality, and this
risk increases as they age. Recent clinical trials have suggested that
older persons benefit from lipid-lowering therapy as much as younger
patients do. Therefore, intervention appears to be justified--as is
greater vigilance in identifying untreated patients.
Am J Cardiol 2000 Feb 15;85(4):484-6
Treating isolated low high-density lipoprotein cholesterol: prescient
Harper CR, Jacobson TA
South Med J 2000 Mar;93(3):283-6 [Texto
Are patients with hyperlipidemia being treated? Investigation of
cholesterol treatment practices in an HMO primary care setting.
Lai LL, Poblet M, Bello C
Department of Pharmacy Administration, Nova Southeastern University, Fort
Lauderdale, Fla 33328, USA.
BACKGROUND: The main study objective was to investigate cholesterol
treatment practices of primary care physicians in a managed care setting.
METHODS: The study was a retrospective review of data with a
quasiexperimental design. The National Cholesterol Education Program-Adult
Treatment Panel II (NCEP-ATP II) guidelines were used as the reference for
conducting a measurement model in the study. Data were randomly selected
via a systematic probability sampling method from a health maintenance
organization (HMO) capitated risk-based contracting medical clinic in
southern Florida. RESULTS: Of the 348 patients selected for the study, 224
(65%) needed either dietary therapy (n = 106) or drug therapy (n = 118).
However, only 16 patients (13.6%) had ever had cholesterol-lowering drug
regimens prescribed during the 5-year study period. CONCLUSIONS: Our
findings indicate that (1) primary care physicians have poorly adopted the
cholesterol management practice recommended by NCEP guidelines and need to
improve their recognition and treatment of hypercholesterolemia; and (2)
the problem of underutilizing prescription medications may be associated
with risk-sharing capitation arrangements between physicians and
Am J Cardiol 2000 Feb 10;85(3A):36A-42A
Optimizing treatment of dyslipidemia in patients with coronary artery
disease in the managed-care environment (the Rocky Mountain Kaiser
Merenich JA, Lousberg TR, Brennan SH, Calonge NB
Department of Endocrinology, Rocky Mountain Kaiser Permanente, Denver,
Colorado 80205, USA.
Rocky Mountain Kaiser Permanente has taken aggressive steps to ensure
optimal treatment of all modifiable cardiac risk factors, especially
low-density lipoprotein (LDL) cholesterol, in patients with coronary
artery disease. In this article, we are presenting (1) the basic rationale
for our approach, (2) the
critical steps translating philosophy into practice, and (3) justification
for all health plans to pursue a similar course. The continuum of
physician-directed disease management systems that have evolved in our
region-one administered by cardiology nurses in the perihospitalization
period and the other by pharmacists in the long-term, outpatient
setting-is then detailed. Although the relatively short duration that our
comprehensive systems have been in place precludes any assessment of their
impact on cardiac death, coronary artery disease events, or coronary
artery disease procedure rates, the improvements in intermediate surrogate
outcomes are promising. Virtually all surveyed patients participating in
our management systems have been "very" or "extremely"
satisfied with their experience. The LDL-cholesterol screening rate in the
approximately 2,500 participants in the programs to date has reached 97%.
Of these patients, 84% have LDL cholesterol <130 mg/dL and 48% <100
mg/dL, and only 15% of those few with LDL cholesterol >130 mg/dL (2.5%
overall) are currently not receiving lipid-lowering therapy. The
proportions of patients on aspirin/antiplatelet and beta-blocker therapy
after myocardial infarction are 97% and 92%, respectively. The
lipid-screening and treatment rates, especially, represent significant
improvement from our own baseline, and compare favorably with outcomes
from other practice settings. In conclusion, health maintenance
organizations have tremendous incentive and the unique opportunity and
ability to develop systems to better manage large numbers of individuals
with coronary artery disease.
Am J Cardiol 2000 Feb 10;85(3A):18A-22A
Lipid management in a private cardiology practice (the Midwest Heart
Brown AS, Cofer LA
Midwest Heart Disease Prevention Center, Midwest Heart Specialists,
Naperville, Illinois, USA.
Emerging evidence that lowering cholesterol levels reduces the incidence
of coronary heart disease led Midwest Heart Specialists to establish a
lipid clinic in 1985. The physician-directed, nurse-managed program was
developed to improve patient adherence to National Cholesterol Education
Program (NCEP) guidelines and provide high-quality preventive services
while preserving productivity for the busy interventional cardiologist who
was the medical director of the program. From 1996 to 1997, Midwest Heart
Specialists was one of 140 medical practices to participate in a national
Quality Assurance Program (QAP). The purpose of the project was to
evaluate the degree of treatment of hyperlipidemia in patients with
coronary heart disease. Although the overall physician practice results
were significantly better than the national averages, the lipid-clinic
results were dramatically more impressive: 100% of the lipid-clinic
patients were on lipid-lowering therapy and 97% of the patients had a
low-density lipoprotein (LDL)-cholesterol level documented on the chart.
Of these, 71% met their LDL goal, as compared with only 11% nationally.
The results of the QAP within the physician practice stimulated the
development of a new practice-wide lipid-management system. This new
systematic approach to lipid management has improved overall lipid
outcomes dramatically. The success of the Cholesterol Management Program
has enhanced the reputation of the practice in the community, tied
high-risk patients and their families to the practice, and improved the
marketability of a full complement of cardiovascular services via Midwest
Am J Cardiol 2000 Feb 10;85(3A):3A-9A
Cholesterol management in the era of managed care.
Department of Clinical Nutrition and Internal Medicine, University of
Texas Southwestern Medical Center at Dallas, 75235-9052, USA.
Several large controlled clinical trials have documented that cholesterol
lowering causes a marked reduction in major coronary events in patients
with established coronary heart disease. Cholesterol lowering thus joins
other proven therapies for risk reduction in secondary prevention. The
need to include
cholesterol-lowering therapy in secondary prevention has been endorsed as
a new practice measure in the Health Plan Employer Data Information Set.
This endorsement ensures that managed care will get behind the effort to
better control cholesterol in patients with coronary heart disease. The
next issue is whether managed care will support cholesterol-lowering
therapy in primary-prevention patients. The patients at highest risk for
developing coronary heart disease are those with noncoronary forms of
atherosclerotic disease, type 2 diabetes, multiple risk factors, and risk
factors plus evidence of advanced subclinical atherosclerosis. Such
patients can be said to have coronary heart disease risk equivalents.
These patients should be good candidates for aggressive cholesterol
management. A strong case can be made for managed-care support for this
approach. Support for treatment of patients at lower risk may be open to
some question, but the current guidelines of the National Cholesterol
Education Program provide a strong rationale for cholesterol management
for primary prevention in the medical setting.
Med Clin North Am 2000 Jan;84(1):23-42
Management of hypercholesterolemia.
Department of Medicine, Oregon Health Sciences University, Portland,
Benefit from the treatment of hyperlipidemia has now been conclusively
documented, and this article has focused on the clinical trial data
supporting diet and drug therapy in adult patients with different
lipoprotein disorders and discussed therapeutic approaches with a focus on
reducing plasma concentrations of LDL cholesterol. National guidelines for
the use of hypolipidemic drugs are strongly supported by the clinical
trials and have appropriately set lower target concentrations of LDL
cholesterol for patients with established atherosclerosis or diabetic
patients as compared with patients with more than two cardiovascular risk
factors or, the lowest risk group, patients without evidence of
atherosclerosis and fewer than two known cardiovascular risk factors. The
goals of therapy in patients with established atherosclerosis are to
prevent further progression and potentially induce regression, whereas in
high-risk patients (e.g., those with heterozygous familial
hypercholesterolemia) without evidence of atherosclerosis, the aims of
therapy are to reduce LDL cholesterol to a concentration at which
subclinical atherosclerosis and xanthomas regress and the patient does not
develop premature cardiovascular disease. Evidence-based medicine strongly
supports clinical benefit from the treatment of hypercholesterolemia in
men and women with and without known coronary artery disease, and the main
goal should be ensure that patients who could benefit from lipid-lowering
therapy are effectively treated and followed to ensure long-term
compliance, efficacy, and safety.
Circulation 2000 Jan 18;101(2):207-13
Current perspectives on statins.
Maron DJ, Fazio S, Linton MF
Department of Medicine, Division of Cardiovascular Medicine, Vanderbilt
University, School of Medicine, Nashville, TN 37232-6300 , USA.
Statins (HMG-CoA reductase inhibitors) are used widely for the treatment
of hypercholesterolemia. They inhibit HMG-CoA reductase competitively,
reduce LDL levels more than other cholesterol-lowering drugs, and lower
triglyceride levels in hypertriglyceridemic patients. Statins are well
tolerated and have an excellent safety record. Clinical trials in patients
with and without coronary heart disease and with and without high
cholesterol have demonstrated consistently that statins reduce the
relative risk of major coronary events by approximately 30% and produce a
greater absolute benefit in patients with higher baseline risk. Proposed
mechanisms include favorable effects on plasma lipoproteins, endothelial
function, plaque architecture and stability, thrombosis, and inflammation.
Mechanisms independent of LDL lowering may play an important role in the
clinical benefits conferred by these drugs and may ultimately broaden
their indication from lipid-lowering to antiatherogenic agents.
JAMA 1999 Dec 1;282(21):2051-7
An evidence-based assessment of the NCEP Adult Treatment Panel II
guidelines. National Cholesterol Education Program.
Ansell BJ, Watson KE, Fogelman AM
Division of General Internal Medicine/Health Services Research, University
of California, Los Angeles, School of Medicine, 90095, USA.
CONTEXT: The Second Report of the National Cholesterol Education Program
(NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood
Cholesterol in Adults (Adult Treatment Panel II) was issued without the
benefit of multiple recently published large clinical trials. OBJECTIVE:
To analyze the panel's guidelines for treatment of high cholesterol levels
in the context of currently available clinical trial results. DATA
SOURCES: MEDLINE was searched for all English-language clinical trial data
from 1993 through February 1999 relating to the effects of cholesterol
treatment on cardiovascular clinical outcomes. STUDY SELECTION: Studies
that were selected for detailed review assessed the effects of cholesterol
lowering on either coronary events, coronary mortality, stroke, and/or
total mortality, preferably by randomized, double-blind,
placebo-controlled design. Selection was by consensus of a general
internist, a lipid clinic director, and a researcher in atherosclerotic
plaque biology. A core of 37 of the 317 initially screened studies were
selected and used as the primary means by which to assess the guidelines.
DATA EXTRACTION: By consensus of the group, only prespecified end points
of trials were included, unless post hoc analysis addressed issues not
studied elsewhere. DATA SYNTHESIS: Recent clinical trial data mostly
support the Adult Treatment Panel II guidelines for cholesterol
management. While existing trials have validated the target low-density
lipoprotein cholesterol (LDL-C) goals in the report, studies are lacking
that address mortality benefit from reduction below these levels. Few
lipid-lowering trials have treated patients with low high-density
lipoprotein cholesterol and/or elevated triglyceride levels with LDL-C
levels at or below treatment goals. CONCLUSIONS: Lipid-lowering therapy
generally should be more aggressively applied to patients with diabetes
and/or at the time of coronary heart disease (CHD) diagnosis. The evidence
for statin use in secondary CHD prevention in postmenopausal women
outweighs current evidence for use of estrogen replacement in this
setting. Further studies are needed to address the effects of lipid
modification in primary prevention of CHD in populations other than
middle-aged men and to study markers of lipid metabolism other than LDL-C.
Am J Med 1999 Aug 23;107(2A):40S-42S
Young adults with hypercholesterolemia.
Kwiterovich PO Jr
Department of Pediatrics, Johns Hopkins University School of Medicine,
Baltimore, Maryland 21287-3654, USA.
Arch Intern Med 1999 Aug 9-23;159(15):1793-802
Clinical outcomes in statin treatment trials: a meta-analysis.
Ross SD, Allen IE, Connelly JE, Korenblat BM, Smith ME, Bishop D, Luo
MetaWorks Inc, Boston, MA 02210, USA. SDR@MetaWork.com
OBJECTIVE: To determine the risk of cardiovascular events and death in
patients receiving statin treatment for cholesterol regulation. METHODS:
Systematic review and meta-analysis of all randomized controlled trials
that were published as of April 15, 1997. Primary or secondary prevention
trials or regression trials were eligible. MAIN OUTCOME MEASURES:
All-cause mortality, fatal myocardial infarction (MI) or stroke, nonfatal
MI or stroke, angina, and withdrawal from the studies. Both random- and
fixed-effects models were run for the outcomes of interests, and results
are expressed as odds ratios (ORs). Sensitivity analyses tested the impact
of the study type and duration, statin treatment type, and control arm
event rates. Intent-to-treat denominators were used whenever they were
available, and the number needed to treat was calculated when appropriate.
RESULTS: Seventeen studies (21 303 patients) were included (2 secondary
prevention studies, 5 mixed primary-secondary prevention population
studies, and 10 regression trials). Treatment groups included lovastatin
(t = 5), pravastatin (t = 10), and simvastatin (t = 3). For all-cause
mortality, the OR was 0.76 (95% confidence interval [CI], 0.67-0.86) in
favor of receiving statin treatment; for fatal MI, the OR was 0.61 (95%
CI, 0.48-0.78); for nonfatal MI, the OR was 0.69 (0.54-0.88); for fatal
stroke, the OR was 0.77 (95% CI, 0.57-1.04); for nonfatal stroke, the OR
was 0.69 (95% CI, 0.54-0.88); and for angina, the OR was 0.70 (95% CI,
0.65-0.76). CONCLUSIONS: Patients who received statin treatment
demonstrated a 20% to 30% reduction in death and major cardiovascular
events compared with patients who received placebo. This advantage was
generally present across study types and statin treatment types and for
patients with less severe dyslipidemias. The benefit in clinical outcomes
was noticeable as early as 1 year.
Arch Intern Med 1999 Aug 9-23;159(15):1670-8
Cholesterol lowering in the elderly population. Coordinating Committee
of the National Cholesterol Education Program.
Grundy SM, Cleeman JI, Rifkind BM, Kuller LH
National Cholesterol Education Program, National Heart, Lung, and Blood
Institute, Bethesda, MD 20892-2480, USA.
The incidence of coronary heart disease (CHD) peaks in the elderly
population.In secondary and primary prevention trials,
cholesterol-lowering therapy reduces risk for CHD in both older and
younger participants. This benefit, therefore, can be extended to the
Curr Opin Cardiol 1999 Jul;14(4):298-302
Evaluation and management of lipid disorders.
Rekhraj S, Hsia J
George Washington University, Division of Cardiology, Washington, DC
Plasma lipids play a key role in the development of atherosclerosis.
Recent trial data support early identification of asymptomatic adults with
high-risk lipid profiles for primary prevention of coronary heart disease.
3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors have been shown
to reduce coronary events in both asymptomatic adults and those with known
coronary heart disease. The optimal plasma low-density lipoprotein
cholesterol for secondary coronary prevention remains controversial. The
Second Report of the Expert Panel on Detection, Evaluation and Treatment
of High Blood Cholesterol in Adults (Adult Treatment Panel II), published
in 1993 by the National Cholesterol Education Program, recommends
guidelines for evaluation and diagnosis of lipids. Subsequently, several
clinical trials have identified populations benefiting from pharmacologic
intervention and new approaches to the management of lipid disorders.
Consequently, these guidelines should be applied with the interval
evidence in mind.
N Engl J Med 1999 Aug 12;341(7):498-511
Drug treatment of lipid disorders.
Northwest Lipid Research Clinic, University of Washington School of
Comment in: N Engl J Med 1999 Dec 23;341(26):2020; discussion 2021
Comment in: N Engl J Med 1999 Dec 23;341(26):2020-1
Clin Cardiol 1999 Jun;22(6 Suppl):II44-8
Pharmacologic management of triglycerides.
Department of Medicine, University of Minnesota, Minneapolis 55455, USA.
Currently available cholesterol-lowering pharmacologic agents have been
studied for their effect on reducing triglyceride levels. The fibrates
increase lipoprotein lipase activity, thereby decreasing the size of
triglyceride-rich particles. High doses of niacin can produce decreases in
very low-density lipoprotein (VLDL) levels, triglyceride-rich particles,
and low-density lipoprotein (LDL) by inhibiting hepatic lipoprotein
synthesis. By increasing LDL-receptor activity, the statins increase the
removal rate of triglyceride-rich particles. Each class of agents produces
various degrees of triglyceride lowering, depending on the existing
baseline level and other factors. Patients with elevated LDL who are also
hypertriglyceridemic should receive statins as first-line therapy. Niacin
may be used as an alternative first-line agent in patients with low LDL
elevations. Combination therapy using other agents may be indicated
depending on the patient's levels of triglycerides and LDL.
Arch Intern Med 1999 May 24;159(10):1049-57
New perspectives on the management of low levels of high-density
Harper CR, Jacobson TA
Department of Medicine, Emory University, Atlanta, GA 30303, USA.
A low serum high-density lipoprotein cholesterol (HDL-C) level is a potent
predictor of coronary heart disease (CHD). It has been estimated that 11%
of US men have isolated low HDL-C levels, and there is uncertainty
regarding the management of these patients. A cause-and-effect
relationship between low HDL-C levels and CHD is supported by
epidemiological, animal, and human clinical studies. We reviewed the
structure and function of HDL-C and its role in preventing
atherosclerosis. We then suggested an approach to the patient with
isolated low HDL-C that may be useful to the primary care physician. An
algorithm was proposed for use in patients with existing CHD, while the
decision to treat patients without CHD was based on their score on the
Framingham Heart Study risk prediction chart.
Comment in: Arch Intern Med 1999 May 24;159(10):1038-40
Comment in: Arch Intern Med 2000 May 8;160(9):1377-8