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[The Multimorbid Patient: Use of New Oral Anticoagulants in Patients with Chronic Kidney Disease].
Mohebbi, N
Praxis. 2018;(13):683-687
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Abstract
The Multimorbid Patient: Use of New Oral Anticoagulants in Patients with Chronic Kidney Disease Abstract. Increasing life expectancy in Western countries is associated with a high prevalence of multiple chronic diseases which is defined by the term "multimorbidity". Many of these patients suffer from chronic kidney disease (CKD) and thrombogenic comorbidities such as atrial fibrillation with the need for oral anticoagulation. For decades vitamin K antagonists have been exclusively prescribed for oral anticoagulation. However, due to altered pharmacokinetics and bioavailability of these drugs in CKD, a significant risk of bleeding exists. The introduction of direct oral anticoagulants as a new and promising alternative to vitamin K antagonists was -especially for CKD patients - highly anticipated. However, data from randomized studies are missing for older patients with advanced CKD. Consequently, a careful evaluation of the risk-benefit ratio is recommended for this sensitive patient population.
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Oral anticoagulation in people with cancer who have no therapeutic or prophylactic indication for anticoagulation.
Kahale, LA, Hakoum, MB, Tsolakian, IG, Matar, CF, Barba, M, Yosuico, VED, Terrenato, I, Sperati, F, Schünemann, H, Akl, EA
The Cochrane database of systematic reviews. 2017;(12):CD006466
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Abstract
BACKGROUND Oral anticoagulants may improve the survival of people with cancer through both an antitumor effect and antithrombotic effect, yet increase the risk of bleeding. OBJECTIVES To evaluate the efficacy and safety of oral anticoagulants in ambulatory people with cancer undergoing chemotherapy, hormonal therapy, immunotherapy or radiotherapy, but otherwise have no standard therapeutic or prophylactic indication for anticoagulation. SEARCH METHODS We conducted a comprehensive literature search in February 2016 that included a major electronic search of Cochrane Central Register of Controlled Trials (CENTRAL) (2016, Issue 1), MEDLINE (Ovid) and Embase (Ovid); handsearching of conference proceedings; checking of references of included studies; a search for ongoing studies; and using the 'related citation' feature in PubMed. As part of the living systematic review approach, we are running continual searches and will incorporate new evidence rapidly after it is identified. This update of the systematic review is based on the findings of a literature search conducted on 14 December 2017. SELECTION CRITERIA Randomized controlled trials (RCTs) assessing the benefits and harms of vitamin K antagonist (VKA) or direct oral anticoagulants (DOAC) in ambulatory people with cancer. These participants are typically undergoing systemic anticancer therapy, possibly including chemotherapy, target therapy, immunotherapy or radiotherapy, but otherwise have no standard therapeutic or prophylactic indication for anticoagulation. DATA COLLECTION AND ANALYSIS Using a standardized form, we extracted data in duplicate on study design, participants, intervention outcomes of interest and risk of bias. Outcomes of interest included all-cause mortality, symptomatic venous thromboembolism (VTE), symptomatic deep vein thrombosis (DVT), pulmonary embolism (PE), major bleeding, minor bleeding and health-related quality of life (HRQoL). We assessed the certainty of evidence for each outcome using the GRADE approach (GRADE Handbook). MAIN RESULTS Of 8545 identified citations, including 7668 unique citations, 16 papers reporting on 7 RCTs fulfilled the inclusion criteria. These trials enrolled 1486 participants. The oral anticoagulant was warfarin in six of these RCTs and apixaban in the seventh RCT. The comparator was either placebo or no intervention. The meta-analysis of the studies comparing VKA to no VKA did not rule out a clinically significant increase or decrease in mortality at one year (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.87 to 1.03; risk difference (RD) 29 fewer per 1000, 95% CI 75 fewer to 17 more; moderate certainty evidence). One study assessed the effect of VKA on thrombotic outcomes. The study did not rule out a clinically significant increase or decrease in PE when comparing VKA to no VKA (RR 1.05, 95% CI 0.07 to 16.58; RD 0 fewer per 1000, 95% CI 6 fewer to 98 more; very low certainty evidence), but found that VKA compared to no VKA likely decreases the incidence of DVT (RR 0.08, 95% CI 0.00 to 1.42; RD 35 fewer per 1000, 95% CI 38 fewer to 16 more; low certainty evidence). VKA increased both major bleeding (RR 2.93, 95% CI 1.86 to 4.62; RD 107 more per 1000, 95% CI 48 more to 201 more; moderate certainty evidence) and minor bleeding (RR 3.14, 95% CI 1.85 to 5.32; RD 167 more per 1000, 95% CI 66 more to 337 more; moderate certainty evidence).The study assessing the effect of DOAC compared to no DOAC did not rule out a clinically significant increase or decrease in mortality at three months (RR 0.24, 95% CI 0.02 to 2.56; RD 51 fewer per 1000, 95% CI 65 fewer to 104 more; low certainty evidence), PE (RR 0.16, 95% CI 0.01 to 3.91; RD 28 fewer per 1000, 95% CI 33 fewer to 97 more; low certainty evidence), symptomatic DVT (RR 0.07, 95% CI 0.00 to 1.32; RD 93 fewer per 1000, 95% CI 100 fewer to 32 more; low certainty evidence), major bleeding (RR 0.16, 95% CI 0.01 to 3.91; RD 28 fewer per 1000, 95% CI 33 fewer to 97 more; low certainty evidence); and minor bleeding (RR 4.43, 95% CI 0.25 to 79.68; RD 0 fewer per 1000, 95% CI 0 fewer to 8 more; low certainty evidence). AUTHORS' CONCLUSIONS The existing evidence does not show a mortality benefit from oral anticoagulation in people with cancer but suggests an increased risk for bleeding.Editorial note: this is a living systematic review. Living systematic reviews offer a new approach to review updating in which the review is continually updated, incorporating relevant new evidence, as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.
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Viewpoint: Stroke Prevention in Recent Guidelines for the Management of Patients with Atrial Fibrillation: An Appraisal.
Potpara, TS, Lip, GYH, Blomström-Lundqvist, C, Chiang, CE, Camm, AJ
The American journal of medicine. 2017;(7):773-779
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Abstract
Formal guidelines play an important role in disseminating the best available evidence knowledge and are expected to provide simple and practical recommendations for the most optimal management of patients with various conditions. Such guidelines have important implications for many disease states, which thereby could be more professionally managed in everyday clinical practice by clinicians with divergent educational backgrounds, and also more easily implemented in wards or outpatient clinics, eliminating inequalities in health care management. In this brief Viewpoint we provide an appraisal on the recommendations pertinent to the prevention of atrial fibrillation-related stroke or systemic thromboembolism, as provided in recently published guidelines for the management of this arrhythmia.
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Practical Considerations for the Use of Direct Oral Anticoagulants in Patients With Atrial Fibrillation.
Stacy, Z, Richter, S
Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. 2017;(1):5-19
Abstract
Atrial fibrillation (AF) is a significant risk factor for stroke and peripheral thromboembolic events (TEs). Preventing blood clots in the heart to reduce stroke and TE risk is a key goal of AF therapy. Traditional stroke risk assessment tools for patients with nonvalvular AF include the CHADS2 and CHA(2)DS(2)-VASc scores, while long-term outcome data with the newer direct oral anticoagulants (DOACs) are emerging. The goals of this review were to assess traditional therapies and existing treatment guidelines and to discuss key pharmacologic properties of the DOACS, noting how these may benefit at-risk patients with AF. This narrative review was developed on the basis of the authors' clinical knowledge, extensive reading of the literature, and broad pharmacy experience in the management of patients with AF. Limitations of oral vitamin K antagonists (VKAs) include slow onset of action, the need for regular monitoring of their anticoagulation effect, significant food and drug interactions, and unpredictable dose-response properties. Key clinical trial data led to the approvals of apixaban, dabigatran etexilate, edoxaban, and rivaroxaban in the United States to reduce the risk of stroke and systemic embolism in patients with nonvalvular AF. With predictable pharmacologic properties and limited drug and/or dietary interactions, the DOACs offer several benefits over traditional oral anticoagulation therapy with VKA. However, they have limitations, including the absence of immediate reversal agents and limited options for monitoring their anticoagulation effects in clinical practice. As experience with the use of DOACs grows, optimized treatment regimens and improved patient care are expected.
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Anticoagulation During Pregnancy: Evolving Strategies With a Focus on Mechanical Valves.
Alshawabkeh, L, Economy, KE, Valente, AM
Journal of the American College of Cardiology. 2016;(16):1804-1813
Abstract
Pregnancy is associated with a hypercoagulable state. Women requiring anticoagulation need careful attention throughout pregnancy and the post-partum period. The choice of anticoagulant therapy, the degree of monitoring, and the therapeutic target should be modulated by balancing the risks and the benefits to the mother and fetus. Many of the available anticoagulant agents may be used safely in pregnancy, but they are disadvantaged by competing efficacy and risks to the mother and fetus. For example, vitamin K antagonists are the most efficacious for preventing mechanical valve thrombosis, but they pose risks to the fetus. Collaborative research that collects patient-level data will help clinicians navigate the intricate process of anticoagulation in pregnancy. Development of anticoagulant agents that are homogeneous, efficacious, safe to the fetus, and not affected by physiological perturbations of pregnancy will have tremendous effect on the outcomes of pregnancy in women who require anticoagulation.
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Direct Oral Anticoagulants for the Management of Thromboembolic Disorders: The Importance of Adherence and Persistence in Achieving Beneficial Outcomes.
Amin, A, Marrs, JC
Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. 2016;(7):605-16
Abstract
Anticoagulation therapy is central to the management of thromboembolic disorders, and the use of direct oral anticoagulants offers several advantages over standard therapy with parenteral heparins and vitamin K antagonists. In phase III clinical trials, the direct oral anticoagulants (given once or twice daily) all demonstrated favorable benefit-risk profiles compared with conventional standard therapy for the treatment and secondary prevention of venous thromboembolism and for stroke prevention in patients with nonvalvular atrial fibrillation. In clinical practice, many factors may influence overall clinical outcomes in patients receiving anticoagulant therapy, including adherence and persistence to the prescribed therapy, which becomes particularly important during long-term therapy. When choosing an anticoagulant for an individual patient, the pharmacological and clinical profile of the anticoagulant, its dosing regimen, and the patient's clinical characteristics (eg, renal function and comorbidities) and preferences should be considered. This review examines the rationale for and clinical evidence of the selected dosing regimens of the direct oral anticoagulants for the treatment of venous thromboembolism and stroke prevention in nonvalvular atrial fibrillation. The potential influence of dosing strategies (eg, once- or twice-daily dosing) and other factors on patient adherence and therapy persistence are also discussed.
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Re-initiation of dabigatran and direct factor Xa antagonists after a major bleed.
Milling, TJ, Spyropoulos, AC
The American journal of emergency medicine. 2016;(11S):19-25
Abstract
Direct oral anticoagulants (DOACs) are a relatively recent addition to the oral anticoagulant armamentarium, and provide an alternative to the use of vitamin K antagonists such as warfarin. Regardless of the type of agent used, bleeding is the major complication of anticoagulant therapy. The decision to restart oral anticoagulation following a major hemorrhage in a previously anticoagulated patient is supported largely by retrospective studies rather than randomized clinical trials (mostly with vitamin K antagonists), and remains an issue of individualized clinical assessment: the patient's risk of thromboembolism must be balanced with the risk of recurrent major bleeding. This review provides guidance for clinicians regarding if and when a patient should be re-initiated on DOAC therapy following a major hemorrhage, based on the existing evidence.
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Extended Anticoagulant and Aspirin Treatment for the Secondary Prevention of Thromboembolic Disease: A Systematic Review and Meta-Analysis.
Marik, PE, Cavallazzi, R
PloS one. 2015;(11):e0143252
Abstract
BACKGROUND Patients who have had an unprovoked deep venous thrombosis (DVT) or pulmonary embolus (PE) are at a high risk for recurrent venous thromboembolism (VTE). Extended "life-long" anticoagulation has been recommended in these patients. However, the risk benefit ratio of this approach is controversial and the role of the direct oral anticoagulants (DOACs) and aspirin is unclear. Furthermore, in some patients with a "weak provoking factor" there is clinical equipoise regarding continuation or cessation of anticoagulant therapy after treatment of the acute VTE event. OBJECTIVE A systematic review and meta-analysis to determine the risks (major bleeding) and benefits (recurrent VTE and mortality) of extended anticoagulation with vitamin k antagonists (VKA), DOACs and aspirin in patients with an unprovoked VTE and in those patients with clinical equipoise regarding continuation or cessation of anticoagulant therapy. In addition, we sought to determine the risk of recurrent VTE events once extended anti-thrombotic therapy was discontinued. DATA SOURCES MEDLINE, Cochrane Register of Controlled Trials, citation review of relevant primary and review articles. STUDY SELECTION Randomized placebo-controlled trials (RCTs) that compared the risk of recurrent VTE in patients with an unprovoked DVT or PE who had been treated for at least 3 months with a VKA or a DOAC and were then randomized to receive an oral anti-thrombotic agent or placebo for at least 6 additional months. We included studies that included patients in whom clinical equipoise existed regarding the continuation or cessation of anticoagulant therapy. DATA EXTRACTION Independent extraction of articles by both authors using predefined data fields, including study quality indicators. Data were abstracted on study size, study setting, initial event (DVT or PE), percentage of patients where the initial VTE event was unprovoked, the number of recurrent VTE events, major bleeds and mortality during the period of extended anticoagulation in the active treatment and placebo arms. In addition, we recorded the event rate once extended treatment was stopped. Meta-analytic techniques were used to summarize the data. Studies were grouped according to the type of anti-thrombotic agent. DATA SYNTHESIS Seven studies which enrolled 6778 patients met our inclusion criteria; two studies evaluated the extended use of Coumadin, three studies evaluated a DOAC and two studies evaluated the use of aspirin. The duration of followup varied from 6 to 37 months. In the Coumadin and aspirin studies 100% of the randomized patients had an unprovoked VTE, while in the DOAC studies between 73.5% and 93.2% of the VTE events were unprovoked. In the control group recurrent VTE occurred in 9.7% of patients compared to 2.8% in the active treatment group (OR 0.21; 95% CI 0.11-0.42, p<0.0001). VKA, DOACs and aspirin significantly reduced the risk of recurrent VTE, with VKA and DOACs being significantly more effective than aspirin. Major bleeding events occurred in 12 patients in the control group (0.4%) and 25 of 3815 (0.6%) patients in the active treatment group (OR 1.64; 95% CI 0.69-3.90, NS). There were 39 (1.3%) deaths in control patients and 33 (0.9%) deaths in the anti-thrombotic group during the treatment period (OR 0.73; 95% CI 0.40-1.33, NS). Patients whose initial VTE event was a PE were more likely to have a recurrent PE than a DVT. The annualized event rate after discontinuation of extended antithrombotic therapy was 4.4% in the control group and 6.5% in the active treatment arm. CONCLUSIONS VKA, DOACs and aspirin significantly reduced the risk of recurrent VTE, with DOACs and VKA being more effective than aspirin. The decision regarding life-long anticoagulation following an unprovoked DVT or PE should depend on the patients' risk for recurrent PE as well as the patients' values and preferences.
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Early detection of vulnerable atherosclerotic plaque for risk reduction of acute aortic rupture and thromboemboli and atheroemboli using non-obstructive angioscopy.
Komatsu, S, Ohara, T, Takahashi, S, Takewa, M, Minamiguchi, H, Imai, A, Kobayashi, Y, Iwa, N, Yutani, C, Hirayama, A, et al
Circulation journal : official journal of the Japanese Circulation Society. 2015;(4):742-50
Abstract
The mortality rate due to rupture of aortic dissection and aortic aneurysm is approximately 90%. Acute aortic rupture can be fatal prior to hospitalization and has proven difficult to diagnose correctly or predict. The in-hospital mortality rate of ruptured aortic aneurysm ranges from 53 to 66%. Emergency surgical and endovascular treatments are the only options for ruptured aortic dissection and aortic aneurysm. No method of systematic early detection or inspection of vessel injury is available at the prevention stage. Regardless of the improvement in many imaging modalities, aortic diameter has remained a major criterion for recommending surgery in diagnosed patients. Previous reports have suggested a relationship between vulnerable plaque and atherosclerotic aortic aneurysm. Non-obstructive angioscopy is a new method for evaluating intimal injury over the whole aorta. It has been used to identify many advanced atherosclerotic plaques that were missed on traditional imaging modalities before aneurysm formation. Non-obstructive angioscopy has shown that atherosclerosis of the aorta begins before that of the coronary artery, which had been noted on autopsy "in vivo". Strong or repetitive aortic injuries might cause sudden aortic disruption. Aortic atheroma is also a risk factor of stroke and perivascular embolism. Detecting aortic vulnerable atherosclerotic plaque on non-obstructive angioscopy may not only clarify the pathogenesis of acute aortic rupture and "aortogenic" thromboemboli and atheroemboli but also play a role in the pre-emptive medicine.
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Direct oral anticoagulants: integration into clinical practice.
Cowell, RP
Postgraduate medical journal. 2014;(1067):529-39
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Abstract
The introduction of direct oral anticoagulants (OACs) for the treatment and prevention of thromboembolic disease represents a shift from the traditional vitamin K antagonist-based therapies, which have been the mainstay of treatment for almost 60 years. A challenge for hospital formularies will be to manage the use of direct OACs from hospital to outpatient settings. Three direct OACs-apixaban, dabigatran and rivaroxaban-are widely approved across different indications, with rivaroxaban approved across the widest breadth of indications. A fourth direct OAC, edoxaban, has also completed phase III trials. Implementation of these agents by physicians will require an understanding of the efficacy and safety profile of these drugs, as well as an awareness of renal function, comedication use, patient adherence and compliance. Optimal implementation of direct OACs in the hospital setting will provide improved patient outcomes when compared with traditional anticoagulants and will simplify the treatment and prevention of thromboembolic diseases.