LA CONSULTA SEMANAL

AGOSTO 2000

CONSULTA

Am Fam Physician 2000 Jun 1;61(11):3371-82 [Texto completo]
Choosing drug therapy for patients with hyperlipidemia.
Safeer RS, Lacivita CL
Division of Family Practice, George Washington University School of Medicine and
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.
Publication Types:
  Review
  Review, tutorial

Am J Cardiol 2000 Jun 22;85(12A):20E-3E
Population benefits of cholesterol reduction: epidemiology, economics, and ethics.
Pearson TA
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.
Publication Types:
  Review
  Review, tutorial

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, Haffner SM
Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.
Publication Types:
  Review
  Review, academic

Geriatrics 2000 May;55(5):22-8 [Texto completo en formato PDF]
Hypercholesterolemia. Is lipid-lowering worthwhile for older patients?
Deedwania PC
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.
Publication Types:
  Review
  Review, tutorial

Am J Cardiol 2000 Feb 15;85(4):484-6
Treating isolated low high-density lipoprotein cholesterol: prescient or premature?
Harper CR, Jacobson TA
Publication Types:
  Editorial
  Review
  Review, tutorial

South Med J 2000 Mar;93(3):283-6 [Texto completo]
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 third-party insurers.

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 Permanente experience).
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.
Publication Types:
  Review
  Review, tutorial

Am J Cardiol 2000 Feb 10;85(3A):18A-22A
Lipid management in a private cardiology practice (the Midwest Heart experience).
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 Heart Specialists.
Publication Types:
  Review
  Review, tutorial

Am J Cardiol 2000 Feb 10;85(3A):3A-9A
Cholesterol management in the era of managed care.
Grundy SM
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.
Publication Types:
  Review
  Review, tutorial

Med Clin North Am 2000 Jan;84(1):23-42
Management of hypercholesterolemia.
Illingworth DR
Department of Medicine, Oregon Health Sciences University, Portland, USA.illingwo@ohsu.edu
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.
Publication Types:
  Review
  Review, tutorial

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. david.maron@mcmail.vanderbilt.edu
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.
Publication Types:
  Review
  Review, tutorial

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. bansell@mednet.ucla.edu
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.
Publication Types:
  Review
  Review, tutorial

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.
Publication Types:
  Review
  Review, tutorial

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 D
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.
Publication Types:
  Meta-analysis

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 elderly.
Publication Types:
  Review
  Review, tutorial

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 20037, USA.
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.
Publication Types:
  Review
  Review, tutorial

N Engl J Med 1999 Aug 12;341(7):498-511
Drug treatment of lipid disorders.
Knopp RH
Northwest Lipid Research Clinic, University of Washington School of Medicine,
Seattle, USA.
Publication Types:
  Review
  Review, tutorial
Comments:
  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.
Hunninghake DB
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.
Publication Types:
  Review
  Review, tutorial

Arch Intern Med 1999 May 24;159(10):1049-57
New perspectives on the management of low levels of high-density lipoprotein cholesterol.
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.
Publication Types:
  Review
  Review, tutorial
Comments:
  Comment in: Arch Intern Med 1999 May 24;159(10):1038-40
  Comment in: Arch Intern Med 2000 May 8;160(9):1377-8