Key articles, guidelines, and consensus papers relative to the treatment of dyslipidemias--2005.

Hypercholesterolemia is a major risk factor for development of coronary heart disease. Proper diagnosis and adequate treatment are vital to reducing morbidity and mortality associated with elevated serum lipid levels. The amount of literature in this area is overwhelming. To aid practitioners and educators in organizing this large body of information, we compiled key articles, guidelines, and consensus papers relative to the treatment of dyslipidemias. Research articles were chosen based on the significance of findings, relevance to practice, quality of research, and timeliness; recent articles were given priority over earlier ones unless they demonstrated groundbreaking findings.

Cost-efficacy analysis of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors based on results of the STELLAR trial: clinical implications for therapeutic selection.

STUDY OBJECTIVE: To compare the cost/1% reduction in low-density lipoprotein cholesterol (LDL) and the cost/patient achieving the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) LDL goal based on the results of the Statin Therapies for Elevated Lipid Levels Compared Across Doses to Rosuvastatin (STELLAR) trial. DESIGN: Cost-efficacy analysis. INTERVENTION: Investigators in the STELLAR trial evaluated percentage reductions in LDL and achievement of the ATP III LDL goal for various doses of atorvastatin, pravastatin, rosuvastatin, and simvastatin. We derived efficacy estimates for these four statins from the results of this trial. We also derived drug acquisition costs from the average wholesale prices to estimate the cost/1% reduction in LDL levels and the cost/patient achieving the ATP III LDL goal. MEASUREMENTS AND MAIN RESULTS: In the STELLAR trial, doses of rosuvastatin produced reductions in LDL significantly greater than those of equivalent milligram/milligram doses of atorvastatin, simvastatin, or pravastatin. The annual acquisition cost/percentage LDL reduction was lower with rosuvastatin at doses of 10 mg (20.92 dollars), 20 mg (18.28 dollars), and 40 mg (17.42 dollars) than with the other statins analyzed. Rosuvastatin also had a lower average cost/patient achieving the ATP III LDL goal over 6 weeks than that of the other statins. CONCLUSION: Although the long-term clinical benefits and safety data from the increased LDL reduction achieved with rosuvastatin remain uncertain, rosuvastatin may be the most cost-effective statin among those analyzed in terms of acquisition cost/1% reduction in LDL levels and in terms of patients achieving ATP III LDL goals. On the basis of the efficacy estimates from the STELLAR trial in conjunction with acquisition cost, a potential cost savings could be realized from the use of rosuvastatin.

Statin-associated peripheral neuropathy: review of the literature.

Various pharmacologic agents are available for the treatment of hypercholesterolemia, including 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, commonly referred to as statins, which offer favorable lipid-lowering effects and reductions in morbidity and mortality. Statins are usually better tolerated than other lipid-lowering agents and therefore have become a mainstay of treatment for hypercholesterolemia. However, recent case reports of peripheral neuropathy in patients treated with statins may have gone unnoticed by health care professionals. To evaluate the possible link between statins and peripheral neuropathy, literature searches using MEDLINE (January 1993--November 2003) and International Pharmaceutical Abstracts (January 1970--June 2002) were performed. Key search terms were statin, neuropathy, and HMG-CoA reductase inhibitors. Based on epidemiologic studies as well as case reports, a risk of peripheral neuropathy associated with statin use may exist; however, the risk appears to be minimal. On the other hand, the benefits of statins are firmly established. These findings should alert prescribers to a potential risk of peripheral neuropathy in patients receiving any of the statins; that is, statins should be considered the cause of peripheral neuropathy when other etiologies have been excluded.

Diabetes transitional care from inpatient to outpatient setting: pharmacist discharge counseling.

PURPOSE: Diabetes transitional care from the inpatient to outpatient setting is understudied. This study evaluated the effect of inpatient pharmacist discharge counseling on outpatient diabetes medication adherence. RESEARCH METHODS: Prospective, randomized, controlled study compared pharmacist discharge counseling (intervention) with usual patient care (control) in 127 patients with established diabetes and an A1C ≥8% who had a provider and medications filled within the county health system. The primary outcome was diabetes medication adherence rate measured using the prescription of days covered (PDC) method. RESULTS: Patients in the intervention, compared with control group, had greater diabetes medication adherence rate 150 days after discharge (55.2% vs 34.8%; P = .002), rate of follow-up visits (60.5% vs 43.9%; P = .01) and reduction in A1C (-1.97% vs +0.114%; P = .003). Being in the intervention group and having greater adherence with follow-up visits correlated independently with lower follow-up A1C. CONCLUSION: Transitional care in the form of inpatient education geared to improve self-management after hospital discharge. This may serve as a paradigm to improve outpatient adherence rate with medications, follow-up visits, and A1C reduction.

Lack of therapeutic interchangeability of HMG-CoA reductase inhibitors.

OBJECTIVE: To review relevant literature and provide an opinion on the class effect of hydroxymethylglutaryl coenzyme A reductase inhibitors (statins). DATA SOURCES: Primary and review articles were identified by MEDLINE search (1990-July 2002). STUDY SELECTION AND DATA EXTRACTION: Editorials, studies, and review articles related to the class effect or therapeutic interchangeability of statins were reviewed. Also included was information that is relevant to this topic. DATA SYNTHESIS: Although statins share common main actions, they may have clinically important differences in terms of efficacy and safety. At fixed or allowable dosages, rosuvastatin, atorvastatin, and simvastatin produced greater low-density lipoprotein cholesterol-lowering effects compared with other statins. Some statins have shown reduction in either cardiovascular and/or total mortality. Statins also differ in their structure, pharmacokinetics, potency, and rate of metabolism, any or all of which may have clinical significance. Although inconclusive, subtle differences in nonlipid effects of some statins may have contributed to positive benefits observed in clinical studies. As a result of drug-related deaths, cerivastatin was withdrawn voluntarily from the market, which may raise the question whether there is therapeutic interchangeability (due to class effect) among statins. CONCLUSIONS: Despite the competition for market share and strategies attempting to identify differences in therapeutic value, few head-to-head comparisons between statins have been performed. The limited, available data suggest that statins are not therapeutically interchangeable.

Niacin-ER and lovastatin treatment of hypercholesterolemia and mixed dyslipidemia.

OBJECTIVE: To review the currently available information on the once-daily combination of niacin extended-release (ER)/lovastatin in the treatment of patients with hypercholesterolemia and mixed dyslipidemia at high risk for cardiovascular events. DATA SOURCES: MEDLINE (1966-July 2002) was searched for primary and review articles. Data from the manufacturer were also included. STUDY SELECTION/DATA EXTRACTION: All articles and product labeling deemed relevant to the combination of niacin and statins (i.e., lovastatin) were included for review. English-language studies selected for inclusion were limited to those with human subjects. DATA SYNTHESIS: The Food and Drug Administration approved a new fixed-dose combination of niacin-ER/lovastatin, which is administered once daily. The efficacy and safety of the combined agent have been proven to be similar to either component used alone or in combination for management of hyperlipidemia and mixed dyslipidemia. CONCLUSIONS: Elevated low-density lipoprotein cholesterol (LDL-C) is independently associated with a higher risk for cardiovascular events. Lowering of elevated LDL-C concentrations with statin monotherapy may be insufficient in patients at high risk for cardiovascular events. In fact, consideration of elevated triglycerides (TGs) and/or low concentrations of high-density lipoprotein cholesterol (HDL-C) in patients with elevated LDL-C places them at greater risk. The addition of niacin may enhance or improve the lipid profile of those who require a further decrease of TGs and/or increase of HDL-C even after stable statin therapy. Niacin-ER offers efficacy similar to that of immediate-release niacin, but minimal myopathy and hepatotoxicity (compared with sustained-release niacin). Although no clinical outcomes are available, current evidence shows that the combination product offers adequate lowering of LDL-C and TGs and increasing HDL-C. The data suggest that therapy with the niacin-ER and lovastatin combination product is safe and does not increase the incidence of adverse effects.

Rosuvastatin for the treatment of patients with hypercholesterolemia.

OBJECTIVE: To review the currently available information on rosuvastatin in the treatment of primary hypercholesterolemia. DATA SOURCES: MEDLEY (2000-January 2001), MEDLIT, MEDLINE, EMBASE, SciSearch, Current Contents, Derwent, Drug, BIOSIS, Adis LMS Drug Alerts, and International Pharmaceutical Abstracts (1994-July 2001) were searched; unpublished data obtained from the manufacturer were also included. STUDY SELECTION: Studies evaluating rosuvastatin including abstracts, proceedings, and data on file from the manufacturer were considered for inclusion. English-language literature was evaluated for pharmacology, pharmacodynamics, pharmacokinetics, therapeutic use, and adverse effects of rosuvastatin. Additional relevant citations were used in the introductory material and discussion section. DATA EXTRACTION: English-language study abstracts selected for inclusion were limited to those on human subjects. Animal data were included only if human data were not available. DATA SYNTHESIS: Resuvastatin, a new synthetic hydroxymethylglutaryl coenzyme A reductase inhibitor (HMG-CoA RI), recently completed Phase III clinical trials. At a dosage of 1-80 mg/d, the drug significantly reduced total cholesterol and low-density-lipoprotein cholesterol (LDL-C) and produced beneficial effects on other lipid parameters as well. Overall, resuvastatin was well tolerated. CONCLUSIONS: In hypercholesterolemic patients, rosuvastatin reduced LDL-C and other lipid parameters to a greater degree than currently available agents. One advantage of rosuvastatin is that it achieves target LDL-C goals in a greater proportion of treated patients with similar adverse events compared with those treated with other HMG-CoA RIs. The potential to reduce risk of coronary heart disease events and decrease mortality as well as cost comparisons with currently used HMG-CoA RIs remains a subject of further investigation.

High-density lipoprotein cholesterol and the role of statins.

Low levels of high-density lipoprotein cholesterol (HDL-C) are currently considered to be a major risk factor for the development of coronary artery disease (CAD). Deficiencies in the HDL metabolic pathway promote atherosclerosis and contribute to CAD. Low HDL-C levels are included in the Framingham 10-year risk assessment for CAD although they are not yet targeted for therapy. Recent clinical trials have shown benefits from raising HDL-C, particularly in patients with lower baseline levels. The statin class of drugs, used primarily to lower the level of low-density lipoprotein-cholesterol, may be able to raise the HDL-C level as well. Statins could potentially affect HDL-C by different modes of action, most importantly by altering reverse cholesterol transport. Among the currently available statins, simvastatin has demonstrated the most consistent ability to raise HDL-C level, but further large-scale studies at an early stage will be needed to prove the antiatherogenic effects of this class of drugs.

Early experiences and clinical implications of drug-eluting stents: part 1.

OBJECTIVE: To review the pathogenesis of in-stent restenosis and the evolution of drug-eluting stents (DES). DATA SOURCES: Using the search terms sirolimus, paclitaxel, and drug-eluting stents, a literature review was conducted to identify peer-reviewed articles and abstracts in MEDLINE (1966-June 2003). Recent meeting abstracts were accessed through the American Heart Association and the American College of Cardiology Web sites. Citations from available articles were also reviewed for additional references. STUDY SELECTION AND DATA EXTRACTION: Published reviews and studies showing the effects of in-stent restenosis and drug-coated and -eluting stents were evaluated and reviewed. DATA SYNTHESIS: Coronary stent implantation is a common form of percutaneous coronary interventions. Approximately 20-30% of patients undergoing stent placement develop restenosis 6 months after the procedure. The primary cause of in-stent restenosis is neointimal proliferation and subsequent accumulation of extracellular matrix, collagen, and macrophages. Eluting stents with an antimitotic agent may reduce the extent of restenosis. Research is ongoing in terms of finding the ideal combination of antimitotic agent, stent, and eluting medium to create the perfect stent. CONCLUSIONS: Research over the last decade has led to a better understanding of the pathogenesis of in-stent restenosis and ways to prevent restenosis. DES are being developed as one of the strategies to prevent restenosis.

Early experiences and clinical implications of restenosis and drug-eluting stents: Part 2.

OBJECTIVE: To review early clinical experience and future implications of drug-eluting stents (DES) in percutaneous coronary interventions. DATA SOURCES: Using the search terms sirolimus, paclitaxel, and drug-eluting stents, a literature review was conducted to identify peer-reviewed articles and abstracts in MEDLINE (1966-June 2003). Recent meeting abstracts were also accessed through the American Heart Association and the American College of Cardiology Web sites. Citations from available articles were reviewed for additional references. STUDY SELECTION AND DATA EXTRACTION: Published reviews and studies showing the effects of in-stent restenosis and drug-coated and -eluting stents were evaluated and reviewed. DATA SYNTHESIS: Current antiplatelet and antithrombotic therapy have proven successful in preventing acute in-stent thrombosis, but not in-stent restenosis. Recently, stents eluted with certain antimitotic agents have demonstrated positive findings in reducing restenosis (eg, sirolimus, paclitaxel-eluting stents) compared with bare-metal stents. However, data regarding long-term benefits and adverse effects are only beginning to accumulate. CONCLUSIONS: While the current clinical efficacy and safety of DES appear promising, further investigations are required to examine long-term efficacy, safety, and cost-effectiveness. Subanalysis of the current data may help to determine the specific patient population that may benefit maximally from DES.

Rasburicase for the treatment and prevention of hyperuricemia.

OBJECTIVE: To review the information currently available on rasburicase for treatment and prevention of hyperuricemia. DATA SOURCES: MEDLINE (1966-August 2002) was searched for primary and review articles. STUDY SELECTION/DATA EXTRACTION: Studies evaluating rasburicase, including abstracts and proceedings, were considered for inclusion. English-language literature was evaluated for the pharmacology, pharmacodynamics, pharmacokinetics, therapeutic use, and adverse effects of rasburicase. DATA SYNTHESIS: Rasburicase, a recombinant urate oxidase, has been shown to be effective in lowering uric acid and preventing uric acid accumulation in patients with hematologic malignancies who had hyperuricemia or who were at high risk for developing hyperuricemia. It has been approved for pediatric use in the US. CONCLUSIONS: In addition to allopurinol, hydration, and urinary alkalinization, rasburicase is a new alternative for the treatment and prevention of hyperuricemia in patients with hematologic malignancies. Its rapid onset of action and the ability to lower preexisting elevated uric acid levels are the advantages of rasburicase compared with allopurinol. It may allow the patient to receive chemotherapy treatment without delay.