Anticoagulation monitoring part 2: Unfractionated heparin and low-molecular-weight heparin

OBJECTIVE: To review the availability, mechanisms, limitations, and clinical application of point-of-care (POC) devices used in monitoring anticoagulation with unfractionated heparin (UFH) and low-molecular-weight heparins (LMWHs). DATA SOURCES: Articles were identified through a MEDLINE search (1966-August 2004), device manufacturer Web sites, additional references listed in articles and Web sites, and abstracts from scientific meetings. STUDY SELECTION AND DATA EXTRACTION: English-language literature from clinical trials was reviewed to evaluate the accuracy, reliability, and clinical application of POC monitoring devices. DATA SYNTHESIS: The activated partial thromboplastin time (aPTT) and activated clotting time (ACT) are common tests for monitoring anticoagulation with UFH. Multiple devices are available for POC aPTT, ACT, and heparin concentration testing. The aPTT therapeutic range for UFH will vary depending upon the reagent and instrument employed. Although recommended by the American College of Chest Physicians Seventh Conference on Antithrombotic and Thrombolytic Therapy, establishing a heparin concentration-derived therapeutic range for UFH is rarely performed. Additional research evaluating anti-factor Xa monitoring of LMWHs using POC testing is necessary. CONCLUSIONS: Multiple POC devices are available to monitor anticoagulation with UFH. For each test, there is some variability in results between devices and between reagents used in the same device. Despite these limitations, POC anticoagulation monitoring of UFH using aPTT and, more often, ACT is common in clinical practice, particularly when evaluating anticoagulation associated with interventional cardiology procedures and cardiopulmonary bypass surgery.     

Old and new anticoagulant drugs: a minireview

Abstract The limits of traditional anticoagulants, such as heparin and warfarin, have prompted the search for new agents for prophylaxis and treatment of arterial and venous thromboembolism, including factor Xa and thrombin inhibitors. These agents can be given orally, and their most significant advantage is that no laboratory monitoring is needed. The anti-Xa inhibitor rivaroxaban and the direct thrombin inhibitor dabigatran etexilate are licensed for prophylaxis of venous thromboembolism (VTE) in high-risk orthopedic surgery. They are at least as safe and effective as heparins but much more expensive. Dabigatran, rivaroxaban, and other agents currently in the pipeline of clinical development have the potential to replace warfarin in the two most frequent indications for anticoagulation, i.e. secondary prophylaxis of VTE and atrial fibrillation. Prevention and treatment of coronary artery thrombosis in patients with ischemic heart disease is another area of investigation for the role of new anticoagulants. These drugs have the potential to meet some currently unmet needs of traditional anticoagulants, but available clinical data warrant confirmation and expansion. Lack of specific antidotes for anticoagulation reversal and the high cost are important limitations of their use.     

Warfarin monitoring with viscoelastic haemostatic assays,thrombin generation,coagulation factors and correlations to Owren and Quick prothrombin time

The anticoagulant warfarin is commonly monitored with prothrombin time (PT). Viscoelastic haemostatic assays (VHA) are primarily used in situations of acute bleeding to guide haemostatic therapy. Much research has focused on VHA monitoring of new oral anticoagulants. However, many patients are still anticoagulated with warfarin and effect of warfarin anticoagulation on VHA is uncertain. The aim of this study was to assess warfarin anticoagulation on three different VHA and compare these findings with prothrombin time (PT), coagulation factor analyses and a thrombin generation assay (TGA). Citrated whole blood was drawn from 80 patients admitted for routine PT-INR Owren. VHA analysis with ROTEM (EXTEM, INTEM and FIBTEM), ReoRox (Fibscreen 1 and 2) and Sonoclot (gbACT+) was performed. Blood was also drawn for plasma analysis with PT (PT-INR Owren and PT Quick), TGA and analysis of factors I, II, VII, IX and X. Extrinsically activated VHA, including ROTEM EXTEM and FIBTEM Clotting Time (CT) and ReoRox Fibscreen1 and 2 clot onset time 1 correlated moderately with PT-INR Owren , with R 0.66–0.71. These four variables were likely to be prolonged above reference interval in patients with prolonged PT-INR Owren >1.2. Two patients with normal ROTEM CTs had Owren PT-INRs >1.5. Warfarin affects extrinsically activated VHA variables of initial clotting. The role of VHA for clinical decision-making in patients planned for invasive procedures, such as spinal/epidural anaesthesia needs further study. None of the recent guidelines on regional anaesthesia include VHA testing to define adequate haemostasis.     

凝血酶生成试验在监测华法林抗凝治疗中的应用

目的 探讨不同抗凝强度口服华法林治疗患者的凝血酶生成情况及其与出血的关系以及凝血酶生成试验在监测华法林抗凝治疗中的应用.方法 采集78例因心脏瓣膜置换术后房颤而口服华法林3个月以上的患者血样,检测凝血酶原时间-国际正常化比值(FT-INR)及凝血酶生成状况.结果 华法林治疗组按PT-INR不同分成三组:I组23例,PT-INR为1.51～2.00;Ⅱ组39例,PT-INR为2.01～3.00;Ⅲ组16例,PT-INR为3.01～4.26.三组凝血酶生成的延迟时间(lagtime)、峰值(peak)、达峰时间(ttpeak)都存在显著性差异(P《0.01),而反映凝血酶总体生成量的指标凝血酶生成潜力(endogenous thrombin potential,ETP),Ⅰ组和Ⅱ组比较差异存在统计学意义(P=0.0001),Ⅱ组和Ⅲ组比较差异无统计学意义(P=0.06).有出血并发症的患者5例,其ETP值小于正常对照组的15%.结论 口服华法林抗凝治疗患者,当PT-INR》3.0后,提高剂量会增加出血风险,但并不降低凝血酶生成量.服用华法林抗凝治疗期间同时检测PT-INR和ETP能更好地反映机体的凝血状态,从而有效地防止出血发生.     

Cholesterol: point-of-care testing

OBJECTIVE: To review the literature regarding point-of-care (POC) cholesterol monitors and describe their role in pharmacy practice. DATA SOURCES: Primary articles were identified by a MEDLINE search (1966-May 2003); references cited in these articles provided additional resources. STUDY SELECTION AND DATA EXTRACTION: All of the articles identified from this search were reviewed, and all information deemed relevant was included. DATA SYNTHESIS: Hyperlipidemia is a well-established risk factor for coronary artery disease, which is the leading cause of death in the US. The use of POC cholesterol monitors may help to improve the identification and management of this disease. Pharmacists may use many of these devices in their practice and are also in an ideal position to provide patient education on selection and use of these monitors and interpretation of the results. CONCLUSIONS: The availability of POC cholesterol monitors has increased in recent years. Based on currently available data, these monitors are best suited for screening purposes and to assist in the management of hyperlipidemia. There is not enough evidence to support the notion that POC cholesterol monitors can replace laboratory or office monitoring. Their application in the diagnosis of hyperlipidemia is also currently limited.     

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.     

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.     

Self-management of anticoagulation

Treatment with vitamin K antagonists (i.e., warfarin or coumadin derivatives) requires repeated monitoring of the intensity of anticoagulation and regular dose adjustment. Nevertheless, many patients are not in the therapeutic target range for a considerable proportion (30-50%) of the time. In addition, repeated laboratory checks and visits to the (anticoagulation) clinic or office are time-consuming and may have a negative impact on patient satisfaction. Recently, reliable portable coagulometers have become available and these devices allow the measurement of the international normalized ratio (INR) from a small drop of capillary blood, thereby enabling patients to self-manage their anticoagulation. Clinical studies show that self-testing of the INR and self-adjusting of the warfarin dose results in a better control of anticoagulation in comparison with regular care by general practitioners or specialists and is at least as good as management by a specialized anticoagulation clinic. Moreover, treatment-related patient satisfaction and quality of life improves in patients performing self-management of anticoagulation.     

Self-management of anticoagulation

Treatment with vitamin K antagonists (i.e., warfarin or coumadin derivatives) requires repeated monitoring of the intensity of anticoagulation and regular dose adjustment. Nevertheless, many patients are not in the therapeutic target range for a considerable proportion (30–50%) of the time. In addition, repeated laboratory checks and visits to the (anticoagulation) clinic or office are time-consuming and may have a negative impact on patient satisfaction. Recently, reliable portable coagulometers have become available and these devices allow the measurement of the international normalized ratio (INR) from a small drop of capillary blood, thereby enabling patients to self-manage their anticoagulation. Clinical studies show that self-testing of the INR and self-adjusting of the warfarin dose results in a better control of anticoagulation in comparison with regular care by general practitioners or specialists and is at least as good as management by a specialized anticoagulation clinic. Moreover, treatment-related patient satisfaction and quality of life improves in patients performing self-management of anticoagulation.     

华法林治疗急性下肢深静脉血栓形成患者凝血酶原-国际标准化比值国人适宜性有效值的初步探讨

目的 初步探讨华法林治疗急性期下肢深静脉血栓形成(DVT)患者适宜国人的凝血酶原-国际标准化比值(PT-INR).方法 选择具有华法林抗凝治疗适应证的DVT患者87例,随机分为A、B 2组,A组(47例)应用华法林,调整PT-INR在1.7～2.5,B组(40例)应用华法林,调整PT-INR在2.0～3.0,比较华法林治疗的有效性及出血并发症的发生率.结果 A组47例患者,46例肢体肿胀明显减退消失,1例无效,经彩超、GT及肿瘤标志物检查,考虑为盆腔肿瘤,有效率为98%;全部患者无明显出血症状.B组40例患者,38例肢体肿胀明显减退消失,2例症状好转不明显,其中Cockett综合征1例,另一例原因不明,有效率为95%;3例出现轻度牙龈及鼻黏膜出血,1例出现胃肠道内出血.2组无肺栓塞发生.结论 国人急性DVT治疗中PT-INR调整在1.7～2.5同样有效,且出血等并发症明显减少.

Abstract：

Objective To explore the suitable range of PT-INR for Chinese people with acute deep venous thrombosis (DVT) treated by warfarin anticoagulation therapy. Methods Eighty seven DVT patients with indications to warfarin anticoagulation therapy were enrolled into the study and divide into two groups randomly. Patients from group A (n=47) took warfarin to adjust the PT-INR to range 1.7-2. 5,and patients from group B (n =40) took warfarin to adjust the PT-INR to range 2. 0-3. 0. The therapeutic effectiveness and the incidence of bleeding complications were compared between two groups. Results Forty-six patients (46/47,98%) had limb swelling symptoms relief in group A with one exception,which was diagnosed as pelvic tumor by ultrasonography,CT and tumor markers examination later. No patient underwent bleeding in group A Thirty eight patients (38/40,93%) had limb swelling symptoms relief in group group B with two exceptions,of which one case had Cockett syndrome and the other one had unknown aetiology. The total effective rate of group B was 95% . As to the complications of this group,3 patients had slight gum and nasal mucous membrane bleeding, 1 patient developed gastrointestinal bleeding. No patients had pulmonary embolism in both groups. Conclusion For Chinese people,anticoagulation therapy of acute deep venous thrombosis to adjust the range of PT-INR to 1.7-2. 5, shows good effectiveness and significantly reduced bleeding complications.     

Aspirin in stroke prevention in nonvalvular atrial fibrillation and stable vascular disease: an era of new anticoagulants

Atrial fibrillation (AF) is a major cause of ischemic stroke, especially in the elderly. There are currently enough data to support the notion that anticoagulation with warfarin or dabigatran is far superior to aspirin in the prevention of stroke or systemic embolism in AF. Aspirin is the preferred modality in patients who are either not candidates for anticoagulation, such as patients with increased risk for bleeding, low-risk patients based on the CHADS2 score or patients who have difficulty in maintaining a therapeutic international normalized ratio. There is no dispute on the recommendations regarding stroke prevention in high-risk patients (CHADS2 risk score of 2 and beyond) with AF. However, there is some controversy regarding the appropriate strategy (anticoagulation vs aspirin) for stroke prevention in low-risk patients (CHA2DS2-VASc score of 0-1). Novel oral anticoagulant drugs (direct thrombin inhibitors and Factor Xa inhibitors) might further diminish the role of aspirin for stroke prevention in AF due to their superior efficacy, lack of need for monitoring of therapeutic effects and lower bleeding risk when compared with warfarin, especially in patients with stable vascular disease.     

The impact of vitamin K-dependent factor depletion by warfarin on platelet-rich thrombosis after deep arterial injury.

Although the central role of thrombin in arterial thrombosis is well established, the efficacy of vitamin K-dependent factor depletion by warfarin at preventing this process has not been established. To assess the efficacy of warfarin in the prevention of arterial thrombosis, two intensities of anticoagulation were compared in a well-characterized porcine model of carotid angioplasty. For 10 days prior to angioplasty, pigs received either high-dose warfarin (n = 9), low-dose warfarin plus aspirin (n = 9), or control tablets (n = 10). Injured arteries were assessed for (111)In-platelet ( x 10(6) cm(-2)) and (125)I-fibrin(ogen) (molecules x 10(12) cm(-2)) deposition and the incidence of macroscopic thrombus. Platelet (30 +/- 7 vs. 332 +/- 137; P = 0.001) and fibrinogen (156 +/- 17 vs. 365 +/- 90; P < 0.05) deposition were significantly reduced in animals receiving high-intensity warfarin whereas low-intensity warfarin/ASA (520 +/- 240 and 1193 +/- 638) was similar to control (P =NS). At the time of angioplasty, the PT-INR and vitamin K-dependent factors varied over a broad range. The greatest reduction of platelet and fibrinogen deposition occurred as the PT-INR increased from 1.0 to 2.2. Increasing the PT-INR beyond 3.0 resulted in little, if any, incremental reduction of either platelet or fibrinogen deposition. Macroscopic thrombus was abolished at PT-INR > 2.2. Despite a broad range of vitamin K factor activities, no single factor was predictive of either platelet or fibrinogen deposition. Warfarin at PT-INR > 2.2 effectively eliminates thrombosis following deep arterial injury. Arterial thrombosis correlates poorly with any single vitamin K-dependent factor but rather appears to be a function of the entire extrinsic coagulation pathway as measured by the PT-INR.     

The potential role of new oral anticoagulants in the prevention and treatment of thromboembolism

Thromboembolic disorders are among the major causes of morbidity and mortality, and anticoagulation remains the cornerstone of prevention and treatment of these disorders. Although effective, the well-established agents have significant drawbacks. Heparin, low molecular weight heparin, and fondaparinux must be given parenterally, which is inconvenient for long-term or home use. The orally administered vitamin K antagonists (such as warfarin) have a slow onset of action, thus requiring bridging therapy with a parenteral agent when immediate anticoagulation is needed (e.g. inpatients with acute deep vein thrombosis). Because vitamin K antagonists produce a variable anticoagulant response as a result of multiple drug-drug and food-drug interactions and genetic polymorphisms, frequent coagulation monitoring and dose adjustment are required to ensure a therapeutic level of anticoagulation, which is inconvenient for both patients and physicians. In the search for new agents to overcome the drawbacks associated with traditional agents, direct Factor Xa inhibitors (e.g. rivaroxaban, apixaban, and edoxaban) and direct thrombin inhibitors (e.g. dabigatran etexilate) have been developed and are undergoing late-stage clinical evaluation for the prevention and treatment of thromboembolic disorders. These new oral agents have already shown promise in large-scale clinical studies and data suggest that we have entered a new era with novel drugs that are closer than ever to the 'ideal anticoagulant'. Because these new oral agents have a rapid onset of action and can be given at fixed doses without the need for routine coagulation monitoring, they may simplify treatment paradigms and are expected to improve overall clinical outcome.     

Novel anticoagulants for stroke prevention in atrial fibrillation and chronic kidney disease

Atrial fibrillation (AF) is about three-times more prevalent in patients with chronic kidney disease and the prevalence of AF increases with the degree of renal impairment. Clinical studies have shown increased risk of stroke, bleeding and death in patients with chronic kidney disease and AF. Despite, this increased risk, anticoagulation is underutilized due to increased bleeding risk in this population. Recently direct thrombin inhibitors and factor Xa inhibitors have been shown to be more efficacious in stroke prevention with reduced bleeding than warfarin. As the usage of these novel anticoagulants increases it is important to understand the data available in regard to these high risk patients.     

Oral anticoagulation: challenges in the case-management setting

By understanding barriers, providing education, and advocating appropriate treatment, case managers play an essential role in the prevention and treatment of thromboembolic disorders. Yet, thromboembolic events such as stroke and deep-vein thrombosis still result in substantial morbidity and mortality despite the availability of effective prophylactic anticoagulation therapy. Although oral warfarin, because of its established efficacy, remains the mainstay in the prevention and treatment of thromboembolic disorders associated with atrial fibrillation, a common antecedent, it is fraught with enduring impediments that hinder effectiveness, safety, and use. With a narrow therapeutic widow, optimal treatment relies on maintaining a tight international normalized ratio (INR) range, usually between 2.0 and 3.0. Lacking intensive anticoagulation clinic monitoring, patients are often outside the therapeutic range, compromising efficacy or safety. Furthermore, the need for frequent and demanding INR monitoring, a slow onset of action, and an elevated risk for drug-drug and food-drug interactions conspire to undermine the use of warfarin, especially in high-risk groups, such as the elderly. Unquestionably, well-tolerated, convenient, and effective alternatives to oral warfarin are needed to improve the management of patients in need of anticoagulation therapy. Several new oral anticoagulants are in development, but only one, ximelagatran, has completed Phase-III development and awaits Food and Drug Administration (FDA) approval. An oral direct thrombin inhibitor, ximelagatran, appears to offer a profile quite different from warfarin: a wide therapeutic window that obviates routine drug-level monitoring and twice-daily oral administration with minimal drug interactions; however, transient liver enzyme elevations remain an unresolved issue. As case managers typically work with those who present with clinical or psychosocial challenges, or both, this treatment approach may provide an alternative that would enhance patient outcomes.     

Ximelagatran for stroke prevention in atrial fibrillation

Atrial fibrillation is the most common sustained cardiac arrhythmia and the most frequently encountered cause of embolic stroke. Vitamin K antagonists (such as warfarin) have represented the cornerstone of anticoagulation practice for the last 60 years. Although highly effective in preventing thromboembolic events among patients with atrial fibrillation, warfarin therapy is limited by a multitude of potential problems. Hence, warfarin is significantly underused in clinical practice, with only half of warfarin-treated patients actually achieving therapeutic anticoagulation in routine clinical practice. Consequently, there is an overwhelming need for an alternative oral anticoagulant for patients with atrial fibrillation that is safer, more practical and effective. Ximelagatran (Exanta, AstraZeneca) is a novel oral direct thrombin inhibitor that is rapidly converted to the active compound melagatran after oral absorption. It has a low potential for drug interactions, anticoagulation monitoring is not required, and it is administered at a fixed twice-daily dose. The Stroke Prevention using the ORal Thrombin Inhibitor in patients with nonvalvular atrial Fibrillation (SPORTIF) III and V trials have together demonstrated the noninferiority of ximelagatran relative to warfarin for the prevention of stroke and embolic events in atrial fibrillation. Unfortunately, initial optimism has been tempered by serious concerns over its safety data in view of its propensity to cause elevation in liver enzymes.     

Ximelagatran for stroke prevention in atrial fibrillation

Atrial fibrillation is the most common sustained cardiac arrhythmia and the most frequently encountered cause of embolic stroke. Vitamin K antagonists (such as warfarin) have represented the cornerstone of anticoagulation practice for the last 60 years. Although highly effective in preventing thromboembolic events among patients with atrial fibrillation, warfarin therapy is limited by a multitude of potential problems. Hence, warfarin is significantly underused in clinical practice, with only half of warfarin-treated patients actually achieving therapeutic anticoagulation in routine clinical practice. Consequently, there is an overwhelming need for an alternative oral anticoagulant for patients with atrial fibrillation that is safer, more practical and effective. Ximelagatran (Exanta®, AstraZeneca) is a novel oral direct thrombin inhibitor that is rapidly converted to the active compound melagatran after oral absorption. It has a low potential for drug interactions, anticoagulation monitoring is not required, and it is administered at a fixed twice-daily dose. The Stroke Prevention using the ORal Thrombin Inhibitor in patients with nonvalvular atrial Fibrillation (SPORTIF) III and V trials have together demonstrated the noninferiority of ximelagatran relative to warfarin for the prevention of stroke and embolic events in atrial fibrillation. Unfortunately, initial optimism has been tempered by serious concerns over its safety data in view of its propensity to cause elevation in liver enzymes.     

Personalizing oral anticoagulant treatment in patients with atrial fibrillation

For decades, warfarin has remained the standard oral anticoagulation for stroke prevention in atrial fibrillation (AF). Three novel oral anticoagulants (NOACs) have been recently approved for stroke prevention in non-valvular AF: dabigatran, rivaroxaban and apixaban. Better pharmacological and clinical profiles make these newcomers a preferable alternative over warfarin. Current AF guidelines do not endorse NOACs over warfarin, or one NOAC over another. Indeed, choice of the anticoagulation regimen should be personalized based on the relative efficacy and safety of different agents across subgroups stratified by thrombotic and bleeding risk, as well as on other clinical factors, including anticoagulation control on warfarin, drug interactions, compliance and need for coagulation monitoring. This review appraises i) the randomized evidence on approved NOACs versus warfarin in AF across subgroups stratified by risk factors of stroke and bleeding and by the anticoagulation level reached on warfarin; and ii) clinical factors impacting on the anticoagulation regimen selection.     

Novel Oral Anticoagulants for Stroke Prevention in Atrial Fibrillation: Focus on Apixaban

Stroke prevention in atrial fibrillation (AF) has been challenging over decades, mostly due to a number of difficulties associated with oral vitamin K antagonists (VKAs), which have been the most effective stroke prevention treatment for a long time. The oral direct thrombin inhibitors (e.g., dabigatran) and oral direct inhibitors of factor Xa (e.g., rivaroxaban, apixaban) have emerged recently as an alternative to VKAs for stroke prevention in AF. These drugs act rapidly, and have a predictable and stable dose-related anticoagulant effect with a few clinically relevant drug-drug interactions. The novel oral anticoagulants are used in fixed doses with no need for regular laboratory monitoring of anticoagulation intensity. However, each of these drugs has distinct pharmacological properties that could influence optimal use in clinical practice. The following phase 3 randomized trials with novel oral anticoagulants versus warfarin for stroke prevention in AF have been completed: the Randomized Evaluation of Long-term Anticoagulant therapy (RE-LY) trial with dabigatran, the Rivaroxaban Once daily oral direct Factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation (ROCKET-AF) trial with rivaroxaban, and the Apixaban for Reduction of Stroke and Other Thromboembolism Events in Atrial Fibrillation (ARISTOTLE) trial with apixaban. Moreover, the Apixaban Versus Acetylsalicylic Acid to prevent Strokes (AVERROES) trial included patients with AF who have failed or were unsuitable for warfarin, and compared apixaban versus aspirin for stroke prevention in AF. Overall, apixaban has two large trials for stroke prevention in AF showing benefits not only over warfarin, but also over aspirin among those patients who have failed or refused warfarin. In the ARISTOTLE trial, apixaban was superior to warfarin in the reduction of stroke or systemic embolism, major bleeding, intracranial hemorrhage, and all-cause mortality, with a similar reduction in the rate of ischemic stroke and better tolerability. When compared with aspirin in the AVERROES trial, apixaban was associated with more effective reduction of stroke, a similar risk of major bleeding, and better tolerability. In this review article, the authors summarize the current knowledge on novel oral anticoagulants and discuss the clinical aspects of their use for stroke prevention in AF, with particular emphasis on apixaban.     

Contemporary anticoagulation therapy in patients undergoing percutaneous intervention

The proper use of anticoagulants is crucial for ensuring optimal patient outcomes post percutaneous interventions in the cardiac catheterization laboratory. Anticoagulant agents such as unfractionated heparin, a thrombin inhibitor; low-molecular weight heparins, predominantly Factor Xa inhibitors; fondaparinux, a Factor Xa inhibitor and bivalirudin, a direct thrombin inhibitor have been developed to target various steps in the coagulation cascade to prevent formation of thrombin. Optimal anticoagulation achieves the correct balance between thrombosis and bleeding and is related to optimal outcomes with minimal complications. This review will discuss the mechanisms and appropriate use of current and emerging anticoagulant therapies used during percutaneous interventions.