scholarly journals Direct Oral Anticoagulants: From Randomized Clinical Trials to Real-World Clinical Practice

2021 ◽  
Vol 12 ◽  
Author(s):  
Roberta Roberti ◽  
Luigi Francesco Iannone ◽  
Caterina Palleria ◽  
Antonio Curcio ◽  
Marco Rossi ◽  
...  

Direct oral anticoagulants (DOACs) are a more manageable alternative than vitamin K antagonists (VKAs) to prevent stroke in patients with nonvalvular atrial fibrillation and to prevent and treat venous thromboembolism. Despite their widespread use in clinical practice, there are still some unresolved issues on optimizing their use in particular clinical settings. Herein, we reviewed the current clinical evidence on uses of DOACs from pharmacology and clinical indications to safety and practical issues such as drugs and food interactions. Dabigatran is the DOAC most affected by interactions with drugs and food, although all DOACs demonstrate a favorable pharmacokinetic profile. Management issues associated with perioperative procedures, bleeding treatment, and special populations (pregnancy, renal and hepatic impairment, elderly, and oncologic patients) have been discussed. Literature evidence shows that DOACs are at least as effective as VKAs, with a favorable safety profile; data are particularly encouraging in using low doses of edoxaban in elderly patients, and edoxaban and rivaroxaban in the treatment of venous thromboembolism in oncologic patients. In the next year, DOAC clinical indications are likely to be further extended.

Author(s):  
Giuseppe Lassandro ◽  
Viviana Valeria Palmieri ◽  
Valentina Palladino ◽  
Anna Amoruso ◽  
Maria Felicia Faienza ◽  
...  

Venous thromboembolism (VTE) in children is a rare occurrence, although in recent decades we have seen an increase due to several factors, such as the rise in survival of subjects with chronic conditions, the use of catheters, and the increased sensitivity of diagnostic tools. Besides inherited thrombophilia, acquired conditions such as cardiovascular diseases, infections, chronic disorders, obesity and malignancy are also common risk factors for paediatric VTE. The treatment of paediatric VTE consists of the use of heparins and/or vitamin K antagonists to prevent dissemination, embolization, and secondary VTE. Randomized clinical trials of direct oral anticoagulants in paediatric VTE are ongoing, with the aim to improve the compliance and the care of patients. We reviewed the physiological and pathological mechanisms underlying paediatric thrombosis and updated the current diagnosis and treatment options.


2018 ◽  
Vol 33 (3) ◽  
pp. 356-363
Author(s):  
Samantha M. Vogel ◽  
Leticia V. Smith ◽  
Evan J. Peterson

Objective: To review evidence behind anticoagulants in cancer-associated venous thromboembolism (VTE) with a focus on low-molecular-weight heparins (LMWH) and the role of direct oral anticoagulants (DOACs). Data Sources: PubMed was searched using terms “venous thromboembolism,” “cancer,” and “anticoagulation.” This search was restricted to clinical trials, meta-analyses, and subgroup analyses. Additional references were identified from reviewing literature citations. Study Selection: English-language prospective and retrospective studies assessing the efficacy and safety of LMWH and DOACs in patients with cancer. Data Analysis: Several trials were analyzed that compared anticoagulation therapies for prevention of recurrent VTE in patients with cancer. Many studies comparing LMWH and vitamin K antagonists (VKAs) found nonsignificant differences between therapies. A single study demonstrated that LMWHs are superior to VKAs. This evidence supporting LMWH for long-term VTE treatment in patients with cancer is based on comparison to VKA, but results are limited by methodological issues, and the benefit of LMWH may be driven by poor control. Subanalyses of DOAC trials suggest these are equally or more effective as VKA in cancer, but this conclusion is underpowered. Conclusion: DOACs have the potential to bypass many challenges with traditional therapy. After analyzing the evidence available, we conclude that after careful consideration of risks and benefits, use of DOACs for VTE treatment are a reasonable option in patients with cancer.


2020 ◽  
Vol 105 (9) ◽  
pp. 2893-2904
Author(s):  
Yi-Hsin Chan ◽  
Lung-Sheng Wu ◽  
Lai-Chu See ◽  
Jia-Rou Liu ◽  
Shang-Hung Chang ◽  
...  

Abstract Objective Patients with hyperthyroidism were excluded from the randomized clinical trials of direct oral anticoagulants (DOACs) for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF). Methods We performed a nationwide retrospective cohort study using data from the Taiwan National Health Insurance Research Database. We enrolled 3213 and 1181 NVAF patients with hyperthyroidism who were taking DOACs and warfarin, respectively, from June 1, 2012 to December 31, 2017. We also enrolled 53 591 and 16 564 NVAF patients without hyperthyroidism, taking DOACs and warfarin, respectively. We used propensity score stabilized weights (PSSWs) to balance covariates across the study groups. We also used 1:4 matching on both taking DOACs, with (n = 3213) and without hyperthyroidism (n = 12 852); and both taking warfarin, with (n = 1181) and without hyperthyroidism (n = 4724). Results After PSSW, DOAC had a comparable risk of ischemic stroke/systemic embolism (IS/SE) and a lower risk of major bleeding (hazard ratio [HR] 0.65; 95% confidential interval [CI], 0.44–0.96; P = 0.0295) than warfarin among patients with hyperthyroidism. There were comparable risks of IS/SE and major bleeding between those patients with and without hyperthyroidism. However, among patients taking warfarin, those with hyperthyroidism had a lower risk of IS/SE than those without hyperthyroidism (HR 0.61; 95% CI, 0.43–0.86; P = 0.0050). Conclusion Among NVAF Asian patients with concomitant hyperthyroidism, DOACs may be an effective and safer alternative to warfarin. Thromboprophylaxis with DOACs may be considered for such patients, and it is important to validate this finding in further prospective study.


2020 ◽  
Vol 25 (5) ◽  
pp. 391-398
Author(s):  
Fabiana Lucà ◽  
Simona Giubilato ◽  
Stefania Angela Di Fusco ◽  
Angelo Leone ◽  
Stefano Poli ◽  
...  

Antithrombotic drugs, which include antiplatelets and anticoagulants, are effective in prevention and treatment of many cardiovascular disorders such as acute coronary syndromes, stroke, and venous thromboembolism and are among the drugs most commonly prescribed worldwide. The advent of direct oral anticoagulants, which are safer alternatives to vitamin K antagonists and do not require laboratory monitoring, has revolutionized the treatment of nonvalvular atrial fibrillation and venous thromboembolism. The combination of oral anticoagulant and antiplatelet therapy is required in many conditions of great clinical impact such as the coexistence of atrial fibrillation and coronary artery disease, with indication to percutaneous coronary intervention. However, strategies that combine anticoagulant and antiplatelet therapies lead to a significant increase in bleeding rates and it is crucial to find the right combination in the single patient in order to optimize the ischemic and bleeding risk. The aim of this review is to explore the evidence and controversies regarding the optimal combination of anticoagulant and antiplatelet therapy through the consideration of past dogmas and new perspectives from recent clinical trials and to propose a tailored therapeutic approach, according to specific clinical scenarios and individual patient characteristics. In particular, we separately explored the clinical settings of stable and acute coronary syndromes and percutaneous revascularization in patients with atrial fibrillation.


Blood ◽  
2020 ◽  
Vol 136 (19) ◽  
pp. 2133-2142
Author(s):  
Saskia Middeldorp ◽  
Wessel Ganzevoort

Abstract One to 2 pregnant women in 1000 will experience venous thromboembolism (VTE) during pregnancy or postpartum. Pulmonary embolism (PE) is a leading cause of maternal mortality, and deep vein thrombosis leads to maternal morbidity, with postthrombotic syndrome potentially diminishing quality of life for a woman’s lifetime. However, the evidence base for pregnancy-related VTE management remains weak. Evidence-based guideline recommendations are often extrapolated from nonpregnant women and thus weak or conditional, resulting in wide variation of practice. In women with suspected PE, the pregnancy-adapted YEARS algorithm is safe and efficient, rendering computed tomographic pulmonary angiography to rule out PE unnecessary in 39%. Low molecular weight heparin (LMWH) in therapeutic doses is the treatment of choice during pregnancy, and anticoagulation (LMWH or vitamin K antagonists [VKAs]) should be continued until 6 weeks after delivery, with a 3-month minimum total duration. LMWH or VKA use does not preclude breastfeeding. Postpartum, direct oral anticoagulants are an option if a woman does not breastfeed and long-term use is intended. Management of delivery, including type of analgesia, requires a multidisciplinary approach and depends on local preferences and patient-specific conditions. Several options are possible, including waiting for spontaneous delivery with temporary LMWH interruption. Prophylaxis for recurrent VTE prevention in subsequent pregnancies is indicated in most women with a history of VTE.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Pardo Sanz ◽  
L M Rincon ◽  
P Guedes Ramallo ◽  
L Belarte ◽  
G De Lara ◽  
...  

Abstract Aims Balance between embolic and bleeding risk is challenging in patients with cancer. There is a lack of specific recommendations for the use of antithrombotic therapy in oncologic patients with atrial fibrillation (AF). We compared the embolic and bleeding risk, the preventive management and the incidence of events between patients with and without cancer. We further evaluated the effectiveness and safety of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) within patients with cancer. Methods The AMBER-AF registry is an observational multicentre study that analysed patients with non-valvular AF treated in Oncology and Cardiology Departments in Spain. 1237 female patients with AF were enrolled: 637 with breast cancer and 599 without cancer. Mean follow-up was 3.1 years. Results Both groups were similar in age, CHA2DS2-VASc and HASB-LED scores. Lack of guidelines recommended therapies was more frequent among patients with cancer. Compared with patients without cancer, adjusted rates of stroke (hazard ratio [95% confidence interval]) in cancer patients were higher (1.56 [1.04–2.35]), whereas bleeding rates remained similar (1.25 [0.95–1.64]). Within the group of patients with cancer, the use of DOACs vs VKAs did not entail differences in the adjusted rates of stroke (0.91 [0.42–1.99]) or severe bleedings (1.53 [0.93–2.53]). Follow-up events Conclusions Antithrombotic management of AF frequently differs in patients with breast cancer. While breast cancer is associated with a higher risk of incident stroke, bleeding events remained similar. Patients with cancer treated with DOACs experienced similar rates of stroke and bleeding as those with VKAs.


2017 ◽  
Vol 117 (02) ◽  
pp. 219-230 ◽  
Author(s):  
Cihan Ay ◽  
Ingrid Pabinger ◽  
Alexander T. Cohen

SummaryVenous thromboembolism (VTE) is a significant health problem in the general population but especially in cancer patients. In this review, we discuss the epidemiology and burden of the disease, the pathophysiology of cancer-associated VTE, and the clinical treatment options for both primary prevention and acute treatment. Overall, the development of VTE in cancer patients is related to increases in morbidity, mortality, and medical costs. However, the incidence of cancer-associated VTE varies due to patient-related factors (e.g. thrombophilia, comorbidities, performance status, history of venous diseases), tumour-related factors (e.g. cancer site, stage, grade), and treatment-related factors (e.g. surgery, chemotherapy, anti-angiogenesis treatment, hormonal and supportive treatment). Furthermore, blood count parameters (e.g. platelets and leukocytes) and biomarkers (e.g. soluble P-selectin and D-dimer) are predictive markers for the risk of VTE in cancer patients and have been used to enhance risk stratification. Evidence suggests that cancer itself is associated with a state of hypercoagulability, driven in part by the release of procoagulant factors, such as tissue factor, from malignant tissue as well as by inflammation-driven activation of endothelial cells, platelets, and leukocytes. In general, low-molecular-weight heparin (LWMH) monotherapy is the standard of care for the management of cancer-associated VTE, as vitamin K antagonists are less effective in cancer patients. Direct oral anticoagulants (DOACs) offer a potentially promising treatment option for cancer patients with VTE, but recommendations concerning the routine use of DOACs should await head-to-head studies with LMWH.


2021 ◽  
Vol 17 (4) ◽  
pp. 584-593
Author(s):  
S. R. Gilyarevsky

The article is devoted to the discussion of the problems of assessing the quality of observational studies in real clinical practice and determining their place in the hierarchy of evidence-based information. The concept of “big data” and the acceptability of using such a term to refer to large observational studies is being discussed. Data on the limitations of administrative and claims databases when performing observational studies to assess the effects of interventions are presented. The concept of confounding factors influencing the results of observational studies is discussed. Modern approaches to reducing the severity of bias in real-life clinical practice studies are presented. The criteria for assessing the quality of observational pharmacoepidemiological studies and the fundamental differences between such studies and randomized clinical trials are presented. The results of systematic reviews of real-life clinical trials to assess the effects of direct oral anticoagulants are discussed. 


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5954-5954
Author(s):  
Dominique Farge

Abstract Venous thromboembolism (VTE) is a major therapeutic concern in cancer patients and the leading cause of death after metastasis. Providing anticoagulant therapy to this patient population is challenging because cancer patients are at increased risk of VTE recurrence and bleeding, and treatment management is often complicated by other co-morbidities that affect choice of anticoagulation. The International Initiative on Thrombosis and Cancer (ITAC-CME) is a multidisciplinary group of International academic clinicians, researchers, and experts dedicated to reducing the global burden of VTE and its consequences in cancer patients. In 2013, the group published international clinical practice guidelines for the treatment and prophylaxis of VTE in cancer (1, 2). In collaboration with CME solutions, an accredited CME provider, ITAC-CME developed a mobile web-based application to promote the international implementation of the 2013 guidelines, in English and French (www.itacc-cme.org). Usage of the app has steadily increased every year since its release. ITAC-CME recently revised its consensus recommendations according to a systematic review of the literature up to January 2016. In particular, the ISTH-endorsed updated recommendations provide a guidance on the use of the direct oral anticoagulants based on the current level of evidence (3). ITAC-CME and CME solutions have updated the web-based application to support the 2016 guidelines. The app also includes several new features, including interactive case-based CME learning activities, with pre- and post-activity practice assessments. These pre- and post-test metrics will be documented to record international clinical practice patterns, and monitor the impact of the app on the adoption of the 2016 guidelines into clinical practice worldwide. Translation of the 2016 updated app into additional languages is planned. The application has been submitted for accreditation with the royal College of Physicians and surgeons of Canada, the American Medical Association, the European Union of Medical Specialists, l' Organisme Gestionnaire du Développement Professionnel Continu, and the European Board for Accreditation in Hematology. 1 Debourdeau P, Farge D, Beckers M, Baglin C, Bauersachs RM, Brenner B, Brilhante D, Falanga A, Gerotzafias GT, Haim N, Kakkar AK, Khorana AA, Lecumberri R, Mandala M, Marty M, Monreal M, Mousa SA, Noble S, Pabinger I, Prandoni P, Prins MH, Qari MH, Streiff MB, Syrigos K, Büller HR, Bounameaux H. International clinical practice guidelines for the treatment and prophylaxis of thrombosis associated with central venous catheters in patients with cancer. J Thromb Haemost. 2013 Jan;11(1):71-80. 2 Farge D, Debourdeau P, Beckers M, Baglin C, Bauersachs RM, Brenner B, Brilhante D, Falanga A, Gerotzafias GT, Haim N, Kakkar AK, Khorana AA, Lecumberri R, Mandala M, Marty M, Monreal M, Mousa SA, Noble S, Pabinger I, Prandoni P, Prins MH, Qari MH, Streiff MB, Syrigos K, Bounameaux H, Büller HR. International clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer.J Thromb Haemost. 2013 Jan;11(1):56-70 3 Farge D, Bounameaux H , Brenner B, Cajfinger F, Debourdeau P, Khorana AA, Pabinger I, Solymoss S, Douketis J, Kakkar A. 2016 International Clinical Practice Guidelines Including Guidance for the Direct Oral Anticoagulants in the Treatment and Prophylaxis of Venous Thromboembolism in Patients With Cancer. Lancet Onccology 2016 (in press) Disclosures No relevant conflicts of interest to declare.


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