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PubMed2026

Direct Oral Anticoagulants as Primary or Secondary Treatment for Heparin-Induced Thrombocytopenia (HIT) and Associated Thromboembolism (HITT)-A Meta-Analysis.

INTRODUCTION: Heparin-induced thrombocytopenia (HIT) is associated with a high risk for thrombosis. The role of direct oral anticoagulants (DOACs) is still emerging and data are limited considering efficacy and safety among patients with HIT. The aim of this review is to evaluate current data on DOACs as primary or secondary treatment among patients with HIT. METHODS: This is a systematic review utilising Pubmed, Scopus and Embase online databases. Eligible studies were published up to December 2024 evaluating DOACs as primary or secondary treatment among patients with HIT and/or associated thrombosis (HITT). Primary outcomes included thrombosis rate (TR) and bleeding rate (BR) during follow-up. RESULTS: A total of 44 publications were included (29 case reports, 5 case studies and 10 cohort studies [n > 10 patients]). Regarding treatment, 19 articles evaluated only rivaroxaban, 7 articles only apixaban, 11 articles only dabigatran and 7 articles more than one regimen. A total of 352 patients were included. Overall, 190 patients (53.8%) were given DOAC as primary treatment whereas 162 patients were given a parenteral treatment first and continued with a DOAC. Mean nadir platelet count at diagnosis was 63 000/μL. HITT rate was 190/352 (53.9%; 8% had arterial thrombosis). Mean follow-up was 7.6 months. TR was 20/352 (Pooled proportion = 0.064 [95% CI = 0.042-0.092]) (30% of them were new thromboses without initial thrombosis), and BR was 9/352 (Pooled proportion = 0.039 [95% CI = 0.022-0.062]). Finally, there was no difference found regarding TR and BR between primary or secondary treatment, and among different regimens. CONCLUSIONS: DOACs are associated with low rates of thrombosis and major bleeding among patients treated for HIT or HITT, either as primary or secondary treatment. However, the certainty of evidence is very low because of the quality and limitations of the available studies.

Humans↗

PubMed2026

Prevalence and Factors Associated with Receiving a Prescription for a Direct Oral Anticoagulant Among Patients with Atrial Fibrillation on Hospice Admission.

Atrial fibrillation (AF) is prevalent in hospice care, but anticoagulation decisions in this population are not well understood. In this cross-sectional study, we described the prevalence and characteristics associated with direct oral anticoagulant (DOAC) prescription on hospice admission. We used electronic health data from adult decedents with AF in a large, for-profit hospice chain in the United States between January 1, 2017 and December 31, 2019. We used multivariable logistic regression with results reported as adjusted odds ratios (AORs) and 95% confidence intervals (CIs). Among 13,233 decedents, mean (standard deviation [SD]) age was 84.2 (9.9) years, 53.6% were female, 65.1% were White, and 56.1% were referred to hospice from a hospital. Mean (SD) CHA2DS2-VASc score were 3.8 (1.4) for males and 4.8 (1.3) for females, and mean (SD) HAS-BLED score was 2.2 (1.0). Overall, 8% of patients received a DOAC prescription on hospice admission. Characteristics associated with receiving a DOAC prescription included PPS scores of ≥ 20% (compared to scores < 20%), and receiving hospice care at home, nursing home, assisted living facility, or residential care home (compared to inpatient hospice). Further studies about the risks and benefits of DOAC use are needed to optimize decision-making in this population.

DOAC↗

PubMed2026

Safety and Effectiveness of Direct Oral Anticoagulants Versus Low-Molecular-Weight Heparin for Cancer-Associated Thrombosis: A Systematic Review and Meta-analysis.

BACKGROUND: Cancer-associated thrombosis is a condition associated with high mortality rates, yet limited evidence exists regarding the safety and effectiveness of low-molecular-weight heparin (LMWH) and direct oral anticoagulants (DOACs), focusing on a fixed follow-up period based on clinical practice guideline recommendations. OBJECTIVE: This study aimed to compare the safety and effectiveness of DOACs versus LMWH in patients with cancer-associated thrombosis over a 6-month follow-up period. METHODS: PubMed, Embase, and Cochrane Library databases were systematically searched up to 30 June, 2025. Recurrent venous thromboembolism, major bleeding, and all-cause mortality were pooled using a random-effects meta-analysis. RESULTS: Seven randomized controlled trials and 28 cohort studies were included in our systematic review. After applying the criteria for a 6-month follow-up period, five randomized controlled trials and 16 cohort studies with 49,824 patients were analyzed in the meta-analysis. In randomized controlled trials, DOACs showed a lower incidence of venous thromboembolism recurrence (relative risk [RR] 0.66, 95% confidence interval [CI] 0.49-0.87) compared with LMWH, with a non-significant increase in major bleeding (RR 1.28, 95% CI 0.87-1.88) and no significant difference in all-cause mortality (RR 1.00, 95% CI 0.86-1.18). Cohort studies demonstrated a lower incidence of venous thromboembolism recurrence (RR 0.69, 95% CI 0.62-0.76) with DOACs, a non-significant reduction in major bleeding (RR 0.85, 95% CI 0.68-1.07), and a lower risk of all-cause mortality (RR 0.47, 95% CI 0.31-0.72). CONCLUSIONS: In patients with cancer-associated thrombosis, DOACs demonstrated a decrease in recurrent venous thromboembolism without increasing the risk of all-cause mortality. A non-significant increase in the risk of major bleeding was recorded in randomized controlled trials, but not in cohort studies. DOACs may provide greater effectiveness for cancer-associated thrombosis compared with LMWH.

Humans↗

PubMed2025

Exome-wide association study of bleeding events in patients receiving direct oral anticoagulants.

BackgroundDirect oral anticoagulants (DOACs) are first-line medications for stroke prevention in non-valvular atrial fibrillation (AF). However, variability in drug response poses risks of hemorrhagic or thromboembolic events.ObjectivesAlthough genetic influences on DOACs safety are increasingly recognized, robust evidence directly linking specific polymorphisms to bleeding risk remains limited.DesignMulti-center observational case-control study including exome-wide association analysis of 196 non-valvular AF patients treated with rivaroxaban or apixaban, comprising 97 with bleeding complications and 99 without.MethodsDOAC plasma concentrations, urinary 6-β-hydroxycortisol and cortisol levels were measured for CYP3A4 phenotyping. Sequencing was performed on the DNBSEQ G-400 platform. Single-nucleotide variant (SNV) associations with bleeding risk were assessed using logistic regression with additive, dominant, and recessive genetic models. Polygenic risk scores (PRSs) were calculated to evaluate cumulative genetic effects.ResultsNo SNVs reached Bonferroni-corrected significance under any model. PRSs showed weak predictive ability for bleeding with apixaban. For rivaroxaban, regression indicated that ln Css min/D + 1 index increased with PRS, age, and 6-β-hydroxycortisol/cortisol ratio, but decreased with higher 6-β-hydroxycortisol and coronary heart disease presence. No statistically significant differences were found for the PharmGKB Level 3 variants rs1045642 (rivaroxaban) and rs2231142 (apixaban). Trends toward statistical significance were observed for the rs2472304-G variant in rivaroxaban users, rs6977165-C in apixaban users, and for the CYP3A4*1/*36 diplotype.ConclusionResidual equilibrium concentration of DOACs, including dose-adjusted, did not independently predict bleeding risk in non-valvular AF patients. Variants rs2472304 and rs6977165 may warrant further investigation as potential contributors to bleeding risk.

Humans↗

PubMed2025

Direct Oral Anticoagulant Transition Strategies Using Anti-Xa Concentrations Upon Intensive Care Unit Admission.

Background: The increased utilization of oral factor Xa inhibitors (FXaI) has led to a growing interest in the clinical utility of FXaI-specific anti-Xa concentrations. Critically ill populations are at risk of bleeding secondary to FXaI accumulation in the setting of end-organ dysfunction. To mitigate this risk, an FXaI anti-Xa concentration-guided approach to transitioning between oral and parenteral anticoagulation has been explored. Objective: To compare the incidence of bleeding upon intensive care unit (ICU) admission between 2 different FXaI transition strategies: concentration versus non-concentration-guided. Methods: We performed a retrospective chart review of patients admitted between January 2019 and May 2022 with objective evidence of FXaI exposure within 48 hours preceding ICU admission. Patients were excluded if they were admitted to the ICU with a primary diagnosis related to a bleeding event, received a non-FXaI anticoagulant 48 hours preceding ICU admission, remained off anticoagulation during their ICU admission, or underwent surgical procedures. The primary outcome was the incidence of major bleeding within 5 days of ICU admission. Thromboembolic events were evaluated as a secondary endpoint. Results: A total of 433 patients (184 concentration-guided vs 249 non-concentration-guided) were included. There was no difference in major bleeding between groups (2.7% in concentration-guided vs 3.6% in non-concentration-guided; P = 0.79). Thromboembolic complications were similar between groups (1.6% in concentration-guided vs 2.0% in non-concentration-guided; P = 1.00) despite a longer time from last FXaI dose to anticoagulant transition in the concentration-guided group (29.9 hours vs 19.4 hours; P < 0.01). Conclusion and relevance: Use of FXaI concentrations to guide anticoagulation transition in the ICU had no impact on major bleeding events or thromboembolic complications. Further analyses are needed to validate FXaI concentration-guided strategies and solidify anti-Xa cutoffs to create a standardized approach to FXaI transitions in the critically ill patient population.

DOAC↗

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↗

PubMed2026

Extended Venous Thromboembolism Prophylaxis After One-Anastomosis Gastric Bypass: A Three-Arm Randomized Trial of Enoxaparin Duration and Rivaroxaban.

BACKGROUND: Venous thromboembolism (VTE) is a serious but preventable complication after bariatric surgery, most of them after hospital discharge. The optimal regimen and duration of post-discharge prophylaxis, particularly the role of direct oral anticoagulants, remain uncertain. OBJECTIVES: To estimate 30-day VTE and bleeding event rates in high-risk patients undergoing one-anastomosis gastric bypass who received 15-day enoxaparin, 30-day enoxaparin, or 30-day rivaroxaban prophylaxis, and to perform exploratory comparisons among the regimens. METHODS: In this randomized, open-label, three-arm clinical trial, high-risk adults undergoing laparoscopic OAGB were randomized before discharge (1:1:1) to enoxaparin 40 mg subcutaneously twice daily for 15 days, enoxaparin 40 mg twice daily for 30 days, or rivaroxaban 10 mg orally once daily for 30 days, after standardized in-hospital enoxaparin and early ambulation. Participants underwent clinical assessment and duplex ultrasonography of the lower-limb and porto-mesenteric veins on postoperative days 15 and 30. The primary outcome was objectively confirmed VTE within 30 days. Bleeding was classified as International Society on Thrombosis and Haemostasis (ISTH) major bleeding or clinically relevant non-major bleeding (CRNMB). Because the expected event rate was low and no non-inferiority or equivalence margin was prespecified, comparisons were interpreted as exploratory. RESULTS: A total of 288 patients were randomized to 15-day enoxaparin (n = 97), 30-day enoxaparin (n = 97), or 30-day rivaroxaban (n = 94). One symptomatic lower-limb deep vein thrombosis occurred in the 15-day enoxaparin group (1.0%; 95% CI, 0.03%-5.6%); no VTE events occurred in the 30-day enoxaparin group (0%; 95% CI, 0%-3.7%) or the rivaroxaban group (0%; 95% CI, 0%-3.8%). Total bleeding occurred in 4/97 patients (4.1%) in each enoxaparin group and 8/94 patients (8.5%) in the rivaroxaban group. The absolute difference in total bleeding between rivaroxaban and 30-day enoxaparin was 4.4% points (95% CI, - 2.9 to 12.2), indicating substantial imprecision. No porto-mesenteric venous thrombosis was detected. CONCLUSION: Only one VTE event occurred, precluding reliable conclusions regarding comparative efficacy or prophylaxis duration. Bleeding estimates were also imprecise and do not establish comparative safety or equivalence between rivaroxaban and enoxaparin. The trial adds descriptive event-rate data from a standardized OAGB pathway, but larger multicenter studies with prespecified comparative hypotheses and assessment of adherence, oral tolerance, and drug exposure are required. The study was approved by the Research Ethics Committee and registered at ClinicalTrials.gov.

Humans↗

PubMed2004

An overview of anticoagulants, antiplatelet agents, and the combination in patients with mechanical heart valves.

Currently, and for the near future, well-managed warfarin appears to be the most effective method to prevent thromboembolism and bleeding in patients with mechanical heart valves. These patients, when in an anticoagulation management service, have 50-90% fewer complications than patients not managed in this way. Further, the complication rate in such settings approximates that in patients with bioprosthetic, tissue valves not receiving anticoagulation. Oral direct thrombin inhibitors are safe and effective in patients with atrial fibrillation, but this is not proven in those with prosthetic heart valves. The idea of using a combination of different antiplatelet agents is attractive on a theoretical basis, but the available data are limited and do not support this approach. Combined aspirin (or another antiplatelet agent) and warfarin has been recommended, but close scrutiny of this combination suggests that it causes more bleeding and may offer no more protection than well-managed warfarin therapy. Recently, interest has been shown in the significance of high-intensity transient signals (HITS), which may represent gaseous or microemboli, and whether therapy to reduce HITS might influence the development of neurological symptoms. However, present data related to HITS are too limited and conflicting to make any firm conclusions.

Anticoagulants↗

PubMed2000

Optimal dosing of subcutaneous unfractionated heparin for the treatment of deep vein thrombosis.

Twice-daily, inpatient, subcutaneous unfractionated heparin is at least as effective and safe as continuous intravenous unfractionated heparin for the treatment of acute deep vein thrombosis. Subcutaneous unfractionated heparin therefore may be suitable for outpatient treatment of deep vein thrombosis. The purpose of this study was to develop a dosing nomogram for a dose each 12 hours (2 doses per day) 12-hourly subcutaneous unfractionated heparin that is suitable for outpatient treatment of acute deep vein thrombosis. A cohort study was performed in patients with acute deep vein thrombosis in two phases. In both phases, the first subcutaneous loading dose of unfractionated heparin was 317 U/kg, and the second dose was 231 U/kg. The activated partial thromboplastin time was measured daily, 6 hours after the morning injection, and subsequent doses of unfractionated heparin were adjusted according to a nomogram, which was modified for phase II. Warfarin was started with unfractionated heparin. In phase I (14 outpatients), activated partial thromboplastin time results were frequently subtherapeutic (9:14) the day after starting unfractionated heparin (day 1), and were frequently supratherapeutic (27:40) after the first 2 days of unfractionated heparin therapy. In phase II (21 patients), to explain the frequently subtherapeutic activated partial thromboplastin time results that were obtained on day 1, the activated partial thromboplastin time results were measured after the initial loading dose. Mean activated partial thromboplastin time results of 86 and 61 seconds were obtained 6 and 12 hours after this dose, suggesting that 317 U/kg is a suitable subcutaneous loading dose. In contrast to phase I, in phase II, unfractionated heparin dose was not increased on day 1 in response to a low activated partial thromboplastin time result. This reduced the frequency of supratherapeutic activated partial thromboplastin time results during the early days of therapy without increasing the frequency of subtherapeutic results. Warfarin therapy had a substantal effect on the activated partial thromboplastin time that appeared to account for a high frequency of supratherapeutic results during the later days of unfractionated heparin therapy; the activated partial thromboplastin time increased by 20 seconds (95% CI, 14-27 seconds) with each increase in the International Normalized Ratio of 1.0. We had limited success at developing a dosing nomogram for subcutaneous unfractionated heparin that reliably achieved activated partial thromboplastin time results within the therapeutic range. However, as oral anticoagulants directly increased activated partial thromboplastin time results, we suggest that adjusting unfractionated heparin dose to achieve prespecified activated partial thromboplastin time results may not be appropriate in patients who are receiving concomitant warfarin therapy.

Acute Disease↗

PubMed1988

Experimental oral anticoagulation by a directly acting thrombin inhibitor (RGH-2958).

D-Phenylalanyl-L-prolyl-L-arginine aldehyde sulfate (RGH-2958), a directly acting synthetic thrombin inhibitor proved to be effective by experimental oral application. The rapid onset of its action has a special importance both from theoretical and practical point of view. Its antiplatelet effect relates to thrombin induced PA and runs parallel with the anticoagulant effect. RGH-2958 significantly reduced the thrombus weight in an experimental thrombosis model in rabbits. In the light of the therapeutic indices of the compound there is a real possibility to open a third way in the prevention and therapy of thrombosis.

Administration, Oral↗

PubMed2005

Ximelagatran: oral direct thrombin inhibition as anticoagulant therapy in atrial fibrillation.

Atrial fibrillation (AF) causes 50,000 to 100,000 ischemic strokes annually in the U.S., most of which could be prevented by oral anticoagulant treatment of the highest-risk patients. The greatest barrier to such treatment is the narrow therapeutic index of the vitamin K antagonists ([VKAs]: warfarin and related coumarin derivatives), the only oral anticoagulant agents currently available. Safe and effective treatment with the VKAs requires careful monitoring, because they interact with many other drugs and foods, and their anticoagulant action is unpredictable. Besides vitamin K, candidate targets for anticoagulant therapy include thrombin, a key prothrombotic mediator. Ximelagatran, the oral direct thrombin inhibitor at the most advanced stage of clinical development, is rapidly absorbed and bioconverted to its active moiety, melagatran-a potent, competitive inhibitor of both free and clot-bound thrombin. Two large clinical trials have demonstrated that fixed-dose oral ximelagatran, 36 mg twice daily, administered without coagulation monitoring, prevents stroke and systemic embolic events in patients with nonvalvular AF as effectively as well-controlled, adjusted-dose warfarin (international normalized ratio 2.0 to 3.0). The overall risk of bleeding was lower with ximelagatran than warfarin, although differences in rates of major hemorrhage were not statistically significant. Elevation of serum alanine aminotransferase levels above 3x the upper limit of normal occurred in approximately 6% of ximelagatran-treated patients but typically returned toward pretreatment levels without associated symptoms. In terms of preventing thromboembolism without hemorrhage, ximelagatran may have a more favorable benefit:risk profile than warfarin for patients with AF.

Administration, Oral↗

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

Bleeding profiles of anticoagulants, including the novel oral direct thrombin inhibitor ximelagatran: definitions, incidence and management.

Ximelagatran is a novel oral direct thrombin inhibitor (oral DTI) that is currently in advanced clinical development for the prevention and treatment of thromboembolic events in a wide range of patient populations and indications. The clinical development of novel anticoagulant therapies requires that treatments be assessed according to both their clinical benefit (reduction of risk of thromboembolic events) and safety profile (primarily bleeding). Definition and assessment of bleeding severity is thus an important factor in clinical trial design. Lack of consistency in bleeding definitions used in different clinical trial programmes makes comparison of bleeding event data difficult. Standard bleeding definitions would be required to make fair comparisons between clinical trials possible. The definitions of bleeding events used in clinical trials of ximelagatran are broadly consistent with those used in many other major trials. Results of phase II and III trials comparing ximelagatran with currently available anticoagulant therapies demonstrate that ximelagatran can be used with fixed dosing with no coagulation monitoring, dose titration, or dose adjustment, without compromising efficacy or safety. The incidences of major bleeding events in clinical trials of ximelagatran have been low and similar to those with other anticoagulant drugs. Adequate treatment in case of emergency situations such as serious bleeding should include cessation of treatment and maintenance of adequate diuresis.

Administration, Oral↗

PubMed1993

Antithrombotic therapy in the secondary prevention of myocardial infarction.

There is now convincing evidence that the majority of myocardial infarcts are caused by acute occlusion of the coronary artery with a thrombus, often originating from a ruptured atherosclerotic plaque. The thrombus is composed of both platelets and fibrin, so it is logical to expect that both antiplatelet and anticoagulant therapy would be effective for the prevention of reinfarction and other thrombotic vascular events following myocardial infarction. A review of clinical trials confirms this suggestion. Aspirin is beneficial in that it reduces vascular mortality by about 12% and total vascular events by 25%. Similarly, oral anticoagulants reduce total mortality by up to 20% and vascular events by about 40%. However, relatively few large scale trials of oral anticoagulants after infarction have been carried out, and the confidence intervals are wider than those for the aspirin trials. In practice aspirin is used more widely than oral anticoagulants as it is easier to administer and control. Only one trial (EPSIM) has directly compared oral anticoagulants and aspirin. This trial showed that both drugs had equal efficacy but that compliance with aspirin was better. Finally, the question of giving antiplatelet agents and anticoagulants together, to block both platelet aggregation and fibrin formation, is considered. A preliminary trial in prosthetic heart-valve patients has been encouraging but more large, long-term trials are required before recommendations can be made, as the use of both drugs together carries an increased risk of severe hemorrhage.

Fibrinolytic Agents↗

PubMed2005

New anticoagulants.

The limitations of heparin and warfarin have prompted the development of new anticoagulant drugs for prevention and treatment of venous and arterial thromboembolism. Novel parenteral agents include synthetic analogs of the pentasaccharide sequence of heparin that mediates its interaction with antithrombin. Fondaparinux, the first synthetic pentasaccharide, is licensed for prevention of venous thromboembolism (VTE) after major orthopedic surgery and for initial treatment of patients with VTE. Idraparinux, a long-acting pentasaccharide that is administered subcutaneously once-weekly, is being compared with warfarin for treatment of VTE and for prevention of cardioembolic events in patients with atrial fibrillation. New oral anticoagulants include direct inhibitors of thrombin, factor Xa and factor IXa. Designed to provide more streamlined anticoagulation than warfarin, these agents can be given without routine coagulation monitoring. Ximelagatran, the first oral direct thrombin inhibitor, is as effective and safe as warfarin for prevention of cardioembolic events in patients with atrial fibrillation. However, ximelagatran produces a three-fold elevation in alanine transaminase levels in 7.9% of patients treated for more than a month, the long-term significance of which is uncertain. Whether other direct thrombin inhibitors or inhibitors of factors Xa or IXa also have this problem is under investigation. After a brief review of coagulation pathways, this paper focuses on new anticoagulants in advanced stages of clinical testing.

Animals↗

PubMed2005

Ximelagatran: a new type of oral anticoagulant.

OBJECTIVES: This assessment sought to evaluate the comparative benefit and adverse effect profile of ximelagatran, as well as the clinical issues surrounding its potential use. METHODS: We performed a Dialog OneSearch across BIOSIS Previews, EMBASE, MEDLINE, PASCAL, and ToxFile to identify published literature. PubMed and The Cochrane Library were also searched. Gray literature was identified by searching a variety of Web sites of health technology assessment and related agencies and their associated databases. The manufacturer's Canadian office, AstraZeneca, was invited to submit information. RESULTS: Ximelagatran is the first oral agent from a new class of anticoagulants called direct thrombin inhibitors. Other oral anticoagulants require routine blood monitoring; ximelagatran does not. Ximelagatran has been evaluated in the areas of venous thromboembolism management, particularly after orthopedic surgery, and stroke prevention in patients with atrial fibrillation. Overall, ximelagatran's efficacy appears comparable to other anticoagulants in these clinical settings. Also, bleeding rates were generally similar between ximelagatran and comparators but, as for warfarin, bleeding risk increases with higher ximelagatran doses. In addition, there is no specific antidote to help manage ximelagatran-induced bleeding. Finally, significantly more patients exposed to long-term ximelagatran developed elevated liver enzymes more than three times the upper normal limit, compared with patients on comparator anticoagulants. CONCLUSIONS: Given its apparent simplicity of use, ximelagatran carries the potential to replace, at least in part, anticoagulants currently used in the management of venous thromboembolism or for preventing stroke in atrial fibrillation patients. However, the safety of ximelagatran will not be fully known without further evaluation and surveillance for potential liver toxicity. There is also a need to evaluate its use in special populations such as patients with renal failure and patients using several concurrent medications.

Administration, Oral↗

PubMed2004

Ximelagatran: the first oral direct thrombin inhibitor.

Oral anticoagulants are often prescribed for long-term prevention and treatment of venous or arterial thromboembolism. The only orally active anticoagulants currently available are the vitamin K antagonists. Although effective, they have a narrow therapeutic window and require routine coagulation monitoring to ensure that a therapeutic level has been achieved. Furthermore, genetic differences in metabolism and multiple food and drug interactions affect the anticoagulant response to vitamin K antagonists. These factors add to the need for routine coagulation monitoring, which is problematic for patients and physicians and costly for the healthcare system. Ximelagatran, the first oral direct thrombin inhibitor, was designed to overcome many of the drawbacks of vitamin K antagonists. Since it produces a predictable anticoagulant response, ximelagatran does not require coagulation monitoring. Phase III clinical trials have evaluated the efficacy and safety of ximelagatran for the prevention and treatment of venous thromboembolism and for the prevention of thromboembolic events in patients with atrial fibrillation. Focusing on ximelagatran, this review will discuss the appropriateness of thrombin as a target for new anticoagulants, compare and contrast direct and indirect thrombin inhibitors and describe the theoretical advantages of direct thrombin inhibitors. It will also review the pharmacology of ximelagatran, discuss the clinical trial results with ximelagatran and provide perspective on the advantages and potential limitations of ximelagatran.

Administration, Oral↗

PubMedDate not supplied

Laboratory assessment of antithrombotic therapy: what tests and if so why?

A critical review is given of the tests available for the assessment of the action of anticoagulants, such as heparins, oral anticoagulants and direct thrombin inhibitors, in patients under antithrombotic therapy. The principle of action and the performance of the thromboplastin time (PT), the activated partial thromboplastin time (aPTT), the whole blood clotting time, the thrombin time, the ecarin clotting time and the endogenous thrombin potential (ETP) is discussed, as well as the evidence behind the accepted therapeutic ranges. The two most common tests, PT and aPTT, respond in an essentially different way to clinically effective anticoagulation with heparin and with oral anticoagulants. This means that they covariate with, but do not themselves represent the essential parameter influenced by anticoagulation. The experimental basis for the widely accepted two times prolongation of the aPTT as an indicator for adequate anticoagulation is shown to be meagre in the case of unfractionated heparin and lacking for the other anticoagulants. Common sources for error in the interpretation of anti-factor Xa- and anti-thrombin activity of heparins are indicated. Extensive experience with new tests like the ecarin clotting time and the ETP is still lacking. On the basis of preliminary data and in view of the importance of the enzymatic action of thrombin in the pathogenesis of thrombosis, the ETP is considered a possible candidate for a common parameter to assess different types of anticoagulants.

Anticoagulants↗