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Biomedical subjects

Edith A Nutescu

Publications and source records attributed to Edith A Nutescu.

At least 37 records · Page 2Linked to original sources
PubMed2004

Emerging options in the treatment of venous thromboembolism.

PURPOSE: The long-term consequences of recurrent venous thromboembolism (VTE) and post-thrombotic syndrome, clinical profiles of traditional and novel antithrombotic agents used to treat VTE, current treatment recommendations for acute symptomatic VTE, clinical experience with newer antithrombotic agents for acute treatment and extended secondary prevention of VTE, and an emerging VTE treatment paradigm are discussed. SUMMARY: Novel antithrombotic agents, with more specific activity on the coagulation cascade, more predictable pharmacodynamics and pharmacokinetics, simpler dosing regimens, and few or no laboratory monitoring requirements, have been developed to overcome limitations associated with some of the nonspecific traditional anticoagulants. Unfractionated heparin (UFH) and low molecular weight heparin (LMWH) are currently the recommended options for initial anticoagulation in patients with acute VTE. Warfarin is the most commonly used agent for chronic anticoagulation. Emerging evidence now also supports the role of factor-Xa inhibitors and oral direct thrombin inhibitors in the acute treatment and extended secondary prevention of VTE. In recent clinical trials, fondaparinux (a synthetic factor-Xa inhibitor) was comparable in efficacy and safety to unfractionated heparin for the treatment of acute symptomatic PE and to the LMWH enoxaparin for treating acute DVT. Ximelagatran, an oral direct thrombin inhibitor, was comparable in safety and efficacy to enoxaparin plus warfarin for treatment of acute VTE (DVT with or without PE). In addition, ximelagatran has been demonstrated to be superior to placebo for the extended secondary prevention of VTE, when continued for an additional 18 months beyond an initial six months of therapy. The benefits of extended anticoagulation for secondary VTE prevention have also been recently demonstrated with both low (INR 1.5-2.0) and regular intensity (INR 2.0-3.0) warfarin therapy. CONCLUSION: A new paradigm for treating VTE is evolving based on the results of recent research to incorporate the use of emerging antithrombotic therapies in the acute treatment period and both traditional and novel agents in the chronic, extended-treatment period.

Clinical Trials as Topic↗
PubMed2004

Ximelagatran: an oral direct thrombin inhibitor.

OBJECTIVE: To present the chemistry, pharmacology, and pharmacokinetics of ximelagatran, an oral direct thrombin inhibitor (DTI), and to review available comparative clinical trial data evaluating its efficacy and safety relative to other antithrombotic agents in the prevention and treatment of thromboembolism. DATA SOURCES: A search of the PubMed and Cochrane databases (1995-August 2004), supplemented by a manual search of article bibliographies, conference abstracts, and data on file from the manufacturer, was conducted. Key search terms were ximelagatran, melagatran, H376/95, and direct thrombin inhibitors. STUDY SELECTION AND DATA EXTRACTION: Pertinent information from available clinical trials, including study design, patient demographics, dosing regimens, anticoagulant comparators, methods for evaluating effectiveness, treatment outcomes, adverse events, and pharmacokinetic and pharmacodynamic evaluations, was extracted. DATA SYNTHESIS: Ximelagatran is an orally administered DTI under development for use in the treatment of venous thromboembolism (VTE), long-term prevention of a second VTE event, stroke secondary to atrial fibrillation, prevention of VTE after orthopedic procedures, and recurrent ischemic events after acute myocardial infarction. CONCLUSIONS: Ximelagatran, in twice-daily doses of 24 or 36 mg, is an alternative to low-molecular-weight heparins or warfarin in thromboprophylaxis following orthopedic knee replacement, atrial fibrillation, or initial treatment of VTE. Improved outcomes versus placebo were seen in the long-term prevention of VTE in patients who completed an initial 6 months of treatment. Liver-related effects need further clarification.

Adult↗
PubMed2004

Impact of prescribing guidelines for inpatient anticoagulation.

BACKGROUND: Anticoagulants are widely used and represent a class of drugs that are problem-prone and have a high potential for adverse patient outcomes. As such, these drugs may be amenable to the use of prescribing guidelines. However, relatively little has been published on the effect of such guidelines on clinical outcomes or costs of care. OBJECTIVE: To assess whether guidelines improve the appropriateness of prescribing, clinical outcomes, and costs associated with use of anticoagulants in a sample of community hospitals in the US. METHODS: A retrospective analysis was performed of data voluntarily collected by 15 hospitals before (July-September 2001) and after (March-May 2002) implementation of anticoagulant prescribing guidelines. Statistical analyses of both patient- and hospital-level variables were conducted. RESULTS: Implementation of the guidelines resulted in a significant increase in the proportion of anticoagulants that were prescribed appropriately (59.8% vs 86.9%; p < 0.001). The guidelines also resulted in a shift in the type of anticoagulants prescribed (decreased use of unfractionated heparin and increased use of low-molecular-weight heparins). There was suggestive evidence, although not statistically significant, that the guidelines resulted in fewer anticoagulant-associated adverse events (total bleeding RR 0.71) and lower costs (savings of $56.15 per patient per day). CONCLUSIONS: While limitations existed with the study design, sufficient benefits were identified to warrant hospitals to consider use of these or similar guidelines on a routine basis. Clearly, additional study in this area would be useful.

Adolescent↗
PubMed2004

Factors that influence prescribing decisions.

BACKGROUND: Strategies to control the quality and cost of medication use are largely dependent on the ability to alter selection of medications. Previous models of prescribing behavior have focused on physicians. In the hospital setting, clinical pharmacists and formulary committee members are also key players in drug therapy decision-making. Differences between physicians, formulary committee members, and clinical pharmacists have not been compared. Knowledge of these differences could have importance in predicting the effectiveness of strategies designed to influence drug use in this setting. OBJECTIVE: To describe and compare the opinions of physicians, clinical pharmacists, and formulary committee members with respect to key factors that influence medication prescribing in community hospitals. METHODS: Physicians, clinical pharmacists, and formulary committee members were solicited to participate. A trained interviewer administered a standardized questionnaire designed to elicit opinions of participants regarding the importance of factors thought to influence drug prescribing. Responses were described using descriptive statistics, and differences between the groups were determined by post hoc analysis. RESULTS: A total of 150 individuals participated in the study. Safety, effectiveness, formulary status, and restrictions on prescribing were considered highly influential by all participants. Physicians rated the availability of drug samples and personal experience higher (more influential on prescribing) than clinical pharmacists and formulary committee members. Clinical pharmacists and formulary committee members rated the influence of recommendations by clinical pharmacists, prescribing guidelines, and cost or cost comparisons higher than physicians. Factors that were drug-related or that involved policy-related programs tended to be more influential than indirect factors. CONCLUSIONS: Those who seek to implement programs to alter medication use should recognize and employ factors that are most influential in the decision-making process. Further, it may be important to consider differences that exist between key participants in the medication use process.

Decision Making↗
PubMed2004

Generic warfarin: implications for clinical practice and perceptions of anticoagulation providers.

For more than 50 years, Coumadin was the dominant warfarin sodium product available in the United States. The approval of generic formulations of warfarin sodium has generated much debate over the therapeutic equivalency and the appropriateness of therapeutic substitution for the innovator product. Despite an AB rating by the Food and Drug Administration (FDA) and recent studies documenting successful switch programs from brand name to generic, much controversy remains concerning the approval process for generic formulations and whether substitution for the innovator product is appropriate. The healthcare professionals affected most by these questions are those working in specialized anticoagulation clinics. We conducted a survey to determine the current practice, experience, and views of healthcare professionals practicing in anticoagulation clinics regarding the substitution of generic products. In addition, the survey sought to identify factors important to healthcare professionals when deciding to use generic or brand name warfarin. Many of these healthcare professionals, primarily pharmacists and nurses, are resistant to generic warfarin substitution and prefer to use the innovator product. These perceptions may change over time as additional data showing comparative therapeutic outcomes between generic and brand name formulations are published.

Anticoagulants↗
PubMed2004

Point of care monitors for oral anticoagulant therapy.

Over recent years, the use of portable coagulation monitors for prothrombin time-International Normalized Ratio (PT-INR) testing has been gaining popularity. Their advantages over traditional methods of monitoring include ease of use, short test duration, faster turnaround time for dosage changes, increased patient convenience by eliminating the need to go to the laboratory for venipuncture, and increased patient-provider interaction. Portable coagulation monitors for PT-INR testing are currently used in various settings, such as anticoagulation clinics, physician offices, at the patient's bedside in hospital wards, and independently by patients at home. Numerous studies have addressed the suitability of these monitors as alternatives to traditional laboratory testing. Various point of care (POC) coagulation monitors have been developed, and many models are commercially available in the United States. Because technology differs among the various devices, accuracy and precision need to be determined for individual devices. The various devices cannot be used interchangeably, and individual device performance cannot be generalized.

Administration, Oral↗
PubMed2004

Direct thrombin inhibitors for anticoagulation.

OBJECTIVE: To review the progress in developing direct thrombin inhibitors (DTIs) for anticoagulation within the context of existing anticoagulation therapies. DATA SOURCES: Searches of MEDLINE (1993-June 2003) were conducted. STUDY SELECTION AND DATA EXTRACTION: We examined English-language articles, human studies, and relevant animal studies, and obtained additional citations from the references of these articles. DATA SYNTHESIS: Because of its pivotal role in hemostasis, thrombin is a key therapeutic target in the treatment and prevention of thromboembolic disorders. Conventional anticoagulant therapies, such as warfarin, unfractionated heparin, and low-molecular-weight heparin, exert their pharmacologic action by indirect thrombin inhibition. Although these agents are effective, each has limitations, prompting a search for more effective, specific, better-tolerated, and convenient anticoagulants. The efficacy and safety of factor Xa inhibitors are being investigated. Furthermore, the development of DTIs such as recombinant hirudin (lepirudin), bivalirudin, and argatroban continues. Challenges in the development of DTIs include establishing a binding affinity for thrombin that is not associated with excessive bleeding, attaining high thrombin specificity, achieving inhibition of both unbound and clot-bound thrombin, and producing an effective, fixed-dose oral anticoagulant to improve the practicality of anticoagulation therapy. Ximelagatran, an oral DTI designed to meet these standards, is currently in Phase III clinical trials. CONCLUSIONS: Significant progress has been made in developing DTIs. The recent emergence of orally administered DTIs may simplify the prevention and treatment of thrombosis.

Administration, Oral↗
PubMed2004

Evolving concepts in the treatment of venous thromboembolism: the role of factor Xa inhibitors.

Anticoagulation is an essential component of the care of patients with venous thromboembolism (VTE). Traditional anticoagulants for the treatment of VTE include unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), and the oral vitamin K antagonist, warfarin. A variety of anticoagulant agents with improved pharmacologic and clinical profiles are emerging and offer benefits over the traditional therapies. One of the most recent advances has been the development of new agents, such as oral direct thrombin inhibitors and factor Xa inhibitors, that have a more selective and targeted effect on the coagulation cascade. Recent clinical trials have evaluated fondaparinux, the first commercially available factor Xa inhibitor, in the treatment of patients with deep vein thrombosis and pulmonary embolism and indicate efficacy and safety as compared with traditional options such as UFH and LMWH. Fondaparinux is a welcomed addition to the available antithrombotic options.

Anticoagulants↗
PubMed2004

Impact of oral direct thrombin inhibitors on anticoagulation clinics.

OBJECTIVES: To characterize the services and activities performed by anticoagulation clinics (ACCs) across the United States, examine the anticipated impact that oral direct thrombin inhibitors (DTIs) will have on the clinical services of ACCs, and elicit possible management strategies to realign services provided by ACCs and opportunities for restructuring clinical services. METHODS: A survey was developed in consultation with content experts in the field, pretested by several ACC providers, and subsequently refined. Surveys were mailed to 400 randomly selected ACC-based providers. RESULTS: The final usable response rate was 34.5% (115 of 333 surveys). Respondents anticipated that the number of patient visits/month would decrease from a median of 336 (interquartile range [IQR] 151-775) to 150 (IQR 71-350, p<0.001) after the introduction of oral DTIs. In addition, time spent on many direct and indirect patient care activities currently performed by ACCs was expected to decline. Respondents indicated that ACCs may find new roles by providing guidance on individual suitability for therapy, managing the transition to oral DTIs, providing education for patients and health care providers on thrombotic disease state management, monitoring patients for recurrent thrombosis and risk of bleeding complications, monitoring patient compliance, and providing counseling and safety surveillance for patients receiving treatment with oral DTIs. CONCLUSION: The advent of oral DTIs is likely to have a significant impact on the structure and delivery of antithrombotic services. Clinics that are proactive and redesign their patient care services to consider emerging anticoagulant agents will be more likely to remain relevant and viable.

Administration, Oral↗
PubMed2004

Transitioning from traditional to novel anticoagulants: the impact of oral direct thrombin inhibitors on anticoagulation management.

Limitations of traditional anticoagulants have led to the need for structured services to provide anticoagulation monitoring. Anticoagulation management services have historically filled this role. Novel antithrombotic agents currently in development have the potential to improve on the limitations of vitamin K antagonists and injectable forms of heparin and to change the field of anticoagulation management. Of the emerging agents, oral direct thrombin inhibitors present the most promise and have a more practical clinical profile. The introduction of the oral direct thrombin inhibitors may present both an opportunity and a threat to anticoagulation management services and anticoagulation service providers. Traditional anticoagulation monitoring services will have to retool for the future if they are to remain relevant in the new era of novel antithrombotic.agents.

Administration, Oral↗
PubMed2003

Tinzaparin: considerations for use in clinical practice.

OBJECTIVE: To evaluate the safety and effectiveness of tinzaparin for the prevention and treatment of venous thromboembolism (VTE). DATA SOURCES: A MEDLINE and PubMed database search (1980-December 2002) was conducted. Only articles written in English were reviewed. STUDY SELECTION AND DATA EXTRACTION: Articles reporting the safety, efficacy, and cost-effectiveness of tinzaparin in humans were evaluated. Emphasis was placed on randomized, controlled trials. DATA SYNTHESIS: Tinzaparin sodium is a low-molecular-weight heparin (LMWH) that exerts its anticoagulant effect through inhibition of factors Xa and IIa and release of tissue factor pathway inhibitor from the vascular epithelium. Tinzaparin is indicated for treatment of acute symptomatic deep-vein thrombosis (DVT), with or without pulmonary embolism. Clinical studies suggest that tinzaparin is also effective for VTE prophylaxis, as well as other indications. Once-daily subcutaneous tinzaparin is equally or more effective than intravenous unfractionated heparin (UFH) for prevention and treatment of VTE, at least as safe as UFH for bleeding complications, and requires little or no monitoring. No dose "cap" is required for obese patients, and no initial dosing adjustments are necessary in elderly and/or renally impaired patients, although some monitoring is recommended. The few comparative data available suggest that tinzaparin efficacy may be comparable to that of other LMWHs; more comparative studies are needed. Pharmacoeconomic studies indicate a favorable cost-benefit ratio. CONCLUSIONS: Tinzaparin is safe and effective for prevention and treatment of DVT. Consistent once-daily dosing may facilitate self-administration of tinzaparin in the outpatient setting.

Animals↗
PubMed2003

Ezetimibe: a selective cholesterol absorption inhibitor.

Ezetimibe is the first agent of a novel class of selective cholesterol absorption inhibitors recently approved by the Food and Drug Administration for treatment in the United States. Ezetimibe inhibits the absorption of biliary and dietary cholesterol from the small intestine without affecting the absorption of fat-soluble vitamins, triglycerides, or bile acids. Ezetimibe localizes at the brush border of the small intestine and decreases cholesterol uptake into the enterocytes. Preclinical studies demonstrated lipid-lowering properties of ezetimibe as monotherapy and showed a synergistic effect in combination with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins). The efficacy and safety of ezetimibe 10 mg/day have been established in phase III clinical trials. In these trials, ezetimibe was investigated as monotherapy, as an add-on to ongoing statin therapy, and as combination therapy with statins in patients with primary hypercholesterolemia. In addition, ezetimibe has been evaluated in patients with homozygous and heterozygous familial hypercholesterolemia and in those with sitosterolemia. When given as monotherapy or in combination with statins or fenofibrate, ezetimibe reduces low-density lipoprotein cholesterol (LDL) by 15-20% while increasing high-density lipoprotein cholesterol by 2.5-5%. Unlike other intestinally acting lipid-lowering agents, ezetimibe does not adversely affect triglyceride levels and, due to its minimal systemic absorption, drug interactions are few. Ezetimibe's side-effect profile resembles that of placebo when given as monotherapy or in combination with statins. In clinical practice, ezetimibe has a role as monotherapy for patients who require modest LDL reductions or cannot tolerate other lipid-lowering agents. In combination therapy with a statin, ezetimibe is used in patients who cannot tolerate high statin doses or in those who need additional LDL reductions despite maximum statin doses.

Animals↗
PubMed2003

Antithrombotic therapy for the treatment of venous thromboembolism.

VTE is a major but often-overlooked healthcare problem resulting in significant morbidity, mortality, and resource expenditures. The efficacy of anticoagulation therapy has been well documented in patients with The availability of LMWHs has advanced treatment of VTE by allowing for effective anticoagulation without the need for dose adjustments and routine monitoring. In addition, patients with uncomplicated DVT can be safely treated in the outpatient setting, allowing for shorter hospital stays and cost savings. LMWHs have been replacing traditional anticoagulants and are now considered the antithrombotic agents of choice in the initial treatment of VTE. Research on additional novel anticoagulants such as DTIs and factor Xa inhibitors is promising. These agents may offer potential benefits over current therapies, but their exact role in clinical practice remains to be determined pending additional ongoing clinical studies. Benefit-to-risk analyses will be necessary for determining how effective novel therapies will compare with established regimens.

Ambulatory Care↗
PubMed2002

Survey of hospital policies regarding low-molecular-weight heparins.

Hospital policies regarding the use of low-molecular-weight heparins (LMWHs) were studied. A questionnaire addressing the formulary status of LMWH products, the use of prescribing guidelines, programs for therapeutic interchange, and policies to promote alternatives to LMWHs when appropriate was prepared. The questionnaire was mailed in January 2001 to pharmacy directors at 70 hospitals located in 19 states. All the hospitals were members of a national group purchasing organization. Forty-nine usable responses were received, for a response rate of 70%. Enoxaparin and dalteparin were the LMWH products most likely to be on the respondents' formularies (98% and 29% of hospitals, respectively). About 29% of the hospitals reported having guidelines on the use of LMWHs. Among hospitals that did not, most indicated that they were considering or would like to implement such guidelines. The most commonly cited barrier to the development and implementation of guidelines was lack of pharmacy personnel. Ten percent of the respondents reported having therapeutic-interchange programs for LMWHs. Cited barriers to therapeutic interchange programs included lack of therapeutic equivalence among products and lack of comparable labeled indications. Policies to promote alternatives to LMWHs were reported by 18% of the respondents. A multihospital survey showed that many hospitals wanted but relatively few had prescribing guidelines for LMWHs.

Dalteparin↗
PubMedDate not supplied

The future of anticoagulation clinics.

The emergence of novel antithrombotic agents may have a dramatic impact on anticoagulation clinics and other providers of anticoagulation services. Of the novel agents currently in development, the oral direct thrombin inhibitor ximelagatran shows the most promise as an agent to improve the field of oral anticoagulation management because it is easier and more convenient to use than warfarin. Ximelagatran is currently being investigated for several indications, including prophylaxis of venous thromboembolism in patients undergoing orthopedic surgery, venous thrombosis treatment, stroke prevention in atrial fibrillation, and acute coronary syndromes. Anticoagulation clinics presently provide systematic, organized management of oral anticoagulation therapy (warfarin in the US) and provide better patient outcomes than usual medical care. The introduction of ximelagatran in patient management may dramatically alter the workload dynamics in anticoagulation clinics. Clinics that will survive the introduction of novel agents will most likely shift from a main focus of warfarin monitoring to thrombotic disease management and coordination of all antithrombotic therapy. Comprehensive Antithrombosis Centers (CAC) will most likely manage patients with thrombotic disorders treated with a range of anticoagulant therapies.

Ambulatory Care Facilities↗
PubMedDate not supplied

New blood thinner offers first potential alternative in 50 years: ximelagatran.

Traditional anticoagulants employed in the treatment of thrombosis include the injectable heparins and oral warfarin. Though effective, these traditional agents are fraught with limitations in their ease of use in the clinical setting. Warfarin, for example, has many pharmacokinetic properties and food-and-drug interactions that result in unpredictable patient response and the need for expensive and time-consuming monitoring of coagulation status. Ximelagatran is a novel, promising, orally active, direct thrombin inhibitor currently in development that, for the first time in 50 years, offers a potential alternative to the mainstay oral agent "warfarin." Advantages of ximelagatran over warfarin include predictable pharmacokinetics and pharmacodynamics, a broad therapeutic window, no routine anticoagulant monitoring, no clinically significant drug interactions, and fixed-dose administration. Ximelagatran has been evaluated for thromboprophylaxis following orthopedic surgery, acute treatment and secondary prevention of venous thrombosis, stroke prevention in atrial fibrillation, and acute coronary syndromes. Results of clinical trials suggest that ximelagatran is equally or more efficacious than warfarin and/or low-molecular-weight heparin therapy without increasing rates of minor or major bleeding. Although postmarketing surveillance will provide the final test of this drug, the future looks promising for addition of a new anticoagulant with the potential to provide excellent efficacy, predictable response, and reduced adverse effects. Pending regulatory approval, ximelagatran may help overcome barriers to appropriate anticoagulant therapy, thereby decreasing morbidity and mortality associated with thrombotic diseases.

Administration, Oral↗