Venous thromboembolic disease in older adults
Wilbert S. Aronow, Jerome L. Fleg, Michael W. Rich in Tresch and Aronow’s Cardiovascular Disease in the Elderly, 2019
Dabigatran is the only direct thrombin inhibitor available at present. It has been evaluated for VTE prophylaxis in THR patients in the RE-NOVATE trials. RE-NOVATE, a 3-month phase 3, randomized, noninferiority study compared the efficacy and safety of two doses of dabigatran. Noninferiority was achieved for both doses for the primary composite endpoint of total VTE (venographically detected or symptomatic VTE) and all-cause mortality (34). The RE-NOVATE II trial examined whether extended prophylaxis (28–35 days) with dabigatran 220 mg was as effective as enoxaparin 40 mg daily after primary THR. The primary outcome occurred in 7.7% of the dabigatran group and in 8.8% of the enoxaparin group, indicating noninferiority (35). Both studies found no significant difference in the rates of bleeding among groups.
Axillo-subclavian venous thrombosis in the setting of thoracic outlet syndrome
Peter Gloviczki, Michael C. Dalsing, Bo Eklöf, Fedor Lurie, Thomas W. Wakefield, Monika L. Gloviczki in Handbook of Venous and Lymphatic Disorders, 2017
A hypercoagulable state has been identified in only 6%–15% of patients treated for axillosubclavian thrombosis. However, following a thrombotic event, the involved venous segment is likely to be thrombogenic, at least transiently. For this reason, full anticoagulation with heparin should be continued postoperatively to prevent recurrent thrombosis. In the immediate post-operative period, patients should receive either a Lovenox or heparin drip while converting to Coumadin. Alternatively, a direct thrombin inhibitor (dabigatran) or selective factor Xa inhibitor (rivaroxaban or apixaban) can be used, although no data exist on efficacy and safety in this situation. Patients should be maintained on anticoagulation for 3–6 months. Duplex ultrasound can be used for surveillance.
Development of palliative medicine in the United Kingdom and Ireland
Eduardo Bruera, Irene Higginson, Charles F von Gunten, Tatsuya Morita in Textbook of Palliative Medicine and Supportive Care, 2015
Due to the risk of life-threatening thromboembolism formation, it is imperative to treat HIT as soon as it is diagnosed. The first step is to discontinue all exposure to heparin-containing products, including catheters coated with heparin. Aside from stopping heparin use, treatment with a direct thrombin inhibitor such as lepirudin, bivalirudin, or argatroban is necessary as there is an increased risk of developing thrombosis. When transitioning to warfarin, current recommendations are to start warfarin once the platelet count has plateaued above 150,000μL-1[22], and the transition should occur after the patient has been adequately anticoagulated [23]. Warfarin treatment is initiated in patients who are in need of longterm anticoagulation with a goal international normalized ratio (INR) of 2-3[24]. Situations that may require long-term anticoagulation include patients with a history of HIT and the sustained presence of antibodies [24] and those at risk of future thrombus formation. Platelet transfusion should be used in patients with HIT and severe thrombocytopenia, only when bleeding or during an invasive procedure with a high risk of bleeding [22].
Rivaroxaban in the cardiovascular world: a direct anticoagulant useful to prevent stroke and venous and arterial thromboembolism
Published in Expert Review of Cardiovascular Therapy, 2018
Leonardo Seoane, Marcia Cortés, María Esther Aris Cancela, Juan Furmento, Adrián Baranchuk, Diego Conde
Actually, DOACs (dabigatran, rivaroxaban, apixaban, and edoxaban) are therapeutic options for cardiologist. Dabigatran is a direct thrombin inhibitor, while rivaroxaban, apixaban, and edoxaban are direct-activated factor X inhibitors. All of them have demonstrated similar efficacy to VKA, particularly in nonvalvular AF, with good safety profile, fewer drug interactions, and a predictable pharmacokinetic response [3–6]. In this scenario and in relation to safety profile, DOACs have fewer intracranial hemorrhages and hemorrhagic strokes (odds ratio (OR) 0.44; 95% confidence interval (CI) 0.32–0.62) [7]. However, in comparison with warfarin, the risk of gastrointestinal bleedings is greater when using dabigatran 150 mg twice daily, rivaroxaban 20 mg once daily, and edoxaban 60 mg once daily [3,4,6]. By contrast, the risk of this kind of bleeds was comparable to warfarin on dabigatran 110 mg twice daily, and on apixaban 5 mg twice daily [4,5]. Regarding efficacy end points, DOACs have been shown to be non-inferior to warfarin in the reduction of stroke and systemic embolism in patients with AF. Anyway, only dabigatran 150 mg twice daily has shown stroke reduction, and only apixaban has reduced significantly all-cause mortality [4,5]. Dabigatran, rivaroxaban, apixaban, and edoxaban are also approved for venous thromboembolism prevention after elective hip or knee replacement surgery, and for the treatment of deep vein thrombosis and PE [8]. In addition, rivaroxaban has been tested at low doses in combination with antiplatelet agents for the prevention of atherothrombotic events in patients with ACS and high ischemic risk [9].
Outpatient treatment of emergency department patients diagnosed with venous thromboembolism
Published in Postgraduate Medicine, 2021
William B. Stubblefield, Jeffrey A. Kline
In the US, four DOAC medications have received clearance to market from the Food and Drug Administration (FDA) for the treatment of VTE: apixaban (Eliquis®), dabigatran (Pradaxa®), edoxaban (Savaysa®), and rivaroxaban (Xarelto®) (Table 2). Three of these medications are factor Xa inhibitors (apixaban, rivaroxaban, and edoxaban) and one is a direct thrombin inhibitor (dabigatran). Approval of each of these medications was the result of several phase III trials that were conducted with each medication being compared to warfarin (Coumadin). The primary endpoints of these studies were VTE recurrence or VTE-related death. In all trials, the DOAC showed similar efficacy and each was noninferior to warfarin in incidence of VTE and VTE-related deaths. DOACs also had lower rates of major bleeding [46], clinically relevant non-major bleeding, and serious adverse events when compared to warfarin [47–52].
Pharmacological management of cerebral ischemia in the elderly
Published in Expert Opinion on Pharmacotherapy, 2021
Adithya Kannan, Mychael Delgardo, William Pennington-FitzGerald, Enoch X. Jiang, Brandon R. Christophe, E Sander Connolly
NOACs function by inhibiting various factors in the coagulation cascade. Dabigatran is a direct thrombin inhibitor, while rivaroxaban, apixaban, and edoxaban inhibit factor Xa. All four have been shown to be safe and more effective than warfarin at preventing stroke or systemic emboli, and therefore all are good candidates for stroke prevention in elderly patients with AF [23]. Of these four NOACs, apixaban is the only one that is excreted mainly by the liver and not the kidneys [23]. Additionally, in a study comparing apixaban to warfarin in 124 end stage renal disease patients on dialysis, the apixaban group had a significantly lower risk of bleeding compared to the warfarin group. No ischemic strokes occurred in either group [46]. These findings suggest that while any of these NOACs are appropriate for preventing AF related ischemic stroke in the elderly, apixaban is best suited for those with compromised renal function.