A comparison of clinical outcome studies among cholesterol-lowering agents.

OBJECTIVE: To review and compare clinical trials of cholesterol-lowering agents that evaluated clinical end points as the primary outcome measure; specifically, to determine whether all agents that decrease cholesterol impact clinical outcomes similarly. DATA SOURCES: Primary articles were identified through a MEDLINE search (1966-February 2001) and through secondary sources. STUDY SELECTION AND DATA EXTRACTION: All of the articles identified from the data sources were evaluated. Articles that included clinical end points as the primary outcome measure were included in this review. DATA SYNTHESIS: Clinical trials were assessed according to study population (primary vs. secondary prevention of coronary artery disease), baseline and follow-up lipid profiles, and clinical outcome data. Both cardiac and noncardiac morbidity and mortality were evaluated. The differences in study populations, study methods, and changes in lipid values were compared and contrasted between trials to evaluate their effect on outcomes. CONCLUSIONS: Niacin and bile acid sequestrants should be considered as add-on therapy when therapeutic goals cannot be attained with a hydroxymethyl glutaryl-coenzyme A reductase inhibitor (stain). Estrogen therapy cannot be recommended solely for cardioprotection. Fibrates are most effective in patients with high baseline triglycerides, low baseline high-density lipoprotein cholesterol, and low to average low-density lipoprotein cholesterol (LDL). Statins are considered first line for the treatment of elevated LDL in both the primary and secondary prevention of coronary heart disease. They are well tolerated, have the strongest data to support their use, and have been shown to decrease total mortality.

Optimizing treatment of dyslipidemia in patients with coronary artery disease in the managed-care environment (the Rocky Mountain Kaiser Permanente experience).

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.

Evaluation of excessive anticoagulation in a group model health maintenance organization.

BACKGROUND: The fourth American College of Chest Physicians Consensus Conference on Antithrombotic Therapy recently published guidelines that included recommendations regarding the management of excessive anticoagulation. Limited data are available to support these recommendations. OBJECTIVES: To assess management and outcomes of excessive anticoagulation in a group model health maintenance organization, compare management with the published guidelines, and analyze the cost of treatment strategies. METHODS: A search of computerized laboratory information identified patients with an international normalized ratio (INR) of greater than 6.0 during the 9-month study. Pertinent data were collected through a retrospective medical record review. Information was concurrently collected for cost analyses. RESULTS: The analysis included 301 episodes of excessive anticoagulation among 248 patients. Most (83%) episodes of elevated INRs were managed conservatively by a temporary discontinuation of warfarin sodium therapy until the INR was in a therapeutic range. Conservative management resulted in no sequelae in 212 (85.1%) of 249 episodes. Two episodes (0.8%) of major bleeding evolved in patients managed conservatively. No sequelae were documented in 23 (44%) of 52 episodes of phytonadione (vitamin K1) administration. Sixteen (31%) episodes of major bleeding were documented, but bleeding occurred before phytonadione administration in all cases. Administering phytonadione resulted in hospital admission for 3 patients--2 (3.8%) because of thromboembolism and 1 (1.9%) for the administration of heparin sodium. Cost-effectiveness analysis determined that treatment with phytonadione is 7 times more costly than conservative management when INRs are between 6.0 and 10.0. CONCLUSIONS: Most episodes of excessive anticoagulation were not managed per consensus guidelines. The higher the INR, the more likely were interventions to adhere to the guidelines. Administering phytonadione to patients with a moderate elevation of INRs (6.0-10.0) may be unnecessary. Based on this study, conservative management is a viable option.

Controversies surrounding estrogen use in postmenopausal women.

OBJECTIVE: To provide an overview of controversies regarding the use of estrogen in postmenopausal women. DATA SOURCES: A MEDLINE search was conducted to identify pertinent literature published since 1990. Recently published textbooks devoted to the subjects of menopause and women's health were also reviewed, particularly their bibliographies. The bibliographies of selected review articles were also reviewed. STUDY SELECTION: Due to the vast amount of literature, only the most relevant published studies were reviewed. Review articles and book chapters authored by researchers of international reputation were also reviewed. DATA EXTRACTION: Identified studies from the primary literature and selected reviews were carefully reviewed. Information regarding the use of estrogen in postmenopausal women was extracted. Particular attention was given to areas of controversy commonly dealt with in the lay media. DATA SYNTHESIS: The number of postmenopausal women in the US will approach 60 million in the next decade. Despite numerous potential benefits, many women elect to not take estrogen due to fear of cancer or poor understanding of the long-term consequences of menopause and the beneficial effects of estrogen replacement therapy. Many women rely on the news media for information about hormone therapy and subsequently become confused regarding the benefits and risks. Estrogen relieves climacteric symptoms such as hot flushes and symptoms related to genitourinary tissue atrophy. Outcomes from controlled clinical trials are lacking, but numerous epidemiologic studies document clinically significant decreases in cardiovascular disease and osteoporotic morbidity and mortality. Unopposed estrogen increases the risk for endometrial cancer, but addition of a progestin for at least 10 days per cycle effectively reduces this risk to that of women who do not take estrogen. The association between postmenopausal estrogen use and breast cancer remains controversial, despite the results of numerous observational studies. This uncertainty regarding estrogen replacement and breast cancer risk can actually be reassuring when placed in proper perspective. CONCLUSIONS: Until some of the controversies surrounding postmenopausal hormone use are resolved, an objective discussion with a knowledgeable healthcare professional regarding the potential benefits and risks will help women make informed decisions regarding estrogen replacement therapy in the postmenopausal years.