scholarly journals Balancing Risk of Thromboembolism and Bleeding in Patients with Cancer: Selecting Anticoagulant Therapy Based on Recent Clinical Trials

EMJ Oncology ◽  
2021 ◽  
Author(s):  
Katarzyna Rygiel
Keyword(s):  
Randomised Controlled Trials ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Oral Route ◽  
Controlled Trials ◽  
Neoplastic Disease ◽  
Patients With Cancer ◽  
The Individual ◽  
Randomised Controlled

Patients with cancer may experience venous thromboembolism (VTE), leading to various medical complications or death, more often than the population without cancer. Moreover, patients with cancer usually experience both higher rates of recurrent VTE and bleeding. For the past decade, low-molecular-weight heparin (LMWH) has been considered a standard therapy for VTE related to cancer; however, daily injections of LMWH have augmented the burden of neoplastic disease and decreased adherence to therapy in some patients. At present, direct oral anticoagulants (DOAC) such as factor Xa inhibitors (e.g., rivaroxaban, edoxaban, and apixaban) have been recommended as a new treatment modality, mostly because of their convenient use (i.e., the oral route of delivery) for the patient population with cancer. Notably, large recent randomised controlled trials that have compared DOACs with LMWH in patients with malignancies have revealed that DOACs represent a valuable alternative to LMWH for the therapy of VTE related to cancer. Despite their unique advantages, the DOACs may not be appropriate for some groups of patients with cancer due to their elevated risk of bleeding, among other factors. This mini-review presents the main findings from some recent randomised controlled trials, comparing the use of DOACs and LMWH for the management of VTE associated with malignancy. It highlights the efficacy, safety, and various other considerations of treatment and prophylaxis of VTE depending on the individual patient context. It provides current guidance on the selection of the optimal anticoagulant for comprehensive and personalised patient care.

Impact of direct oral anticoagulants compared with warfarin in patients on dialysis: a meta-analysis

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
R Sakurai
Keyword(s):  
Major Bleeding ◽  
Randomised Controlled Trials ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Cochrane Library ◽  
Controlled Trials ◽  
Systemic Embolism ◽  
Clinical Endpoints ◽  
Randomised Controlled

Abstract Background Direct oral anticoagulants have been demonstrated to have advantages in several patient populations compared with warfarin. However, the safety and efficacy are controversial between direct oral anticoagulants and warfarin in patients with chronic kidney disease, especially on dialysis, who have been excluded from randomised controlled trials. Purpose The purpose of this study was to investigate the safety and the efficacy of direct oral anticoagulants as compared to warfarin in patients on dialysis. Methods A meta-analysis was conducted on clinical studies in patients requiring oral anticoagulation and dialysis. PubMed, the Cochrane Library, and Web of Science were queried for the terms “dialysis”, “warfarin”, and “apixaban OR dabigatran OR rivaroxaban OR edoxaban”. The same terms or relevant studies were also queried on the website of the U.S. National Institute of Health and relevant reviews. The clinical endpoints were stroke/systemic embolism and major bleeding. Pooled estimates were calculated using a random-effects model. Results Six observational studies (18487 patients) were included in this study. The risk of major bleeding (odds ratio (OR) 0.45; 95% confidence interval (CI) 0.31–0.65; p<0.01) was lower in patients on direct oral anticoagulants compared to those on warfarin, whereas the risk of stroke/systemic embolism (OR0.63; 95% CI 0.30–1.33; p=0.23) was similar between the two types of anticoagulant. Conclusions Direct oral anticoagulants are associated with a lower risk of major bleeding and a similar risk of stroke/systemic embolism compared to warfarin in patients on dialysis. To validate these findings, randomised controlled trials are warranted. Funding Acknowledgement Type of funding source: None

scholarly journals Practical Implementation of Anticoagulation Strategy for Patients Undergoing Cardioversion of Atrial Fibrillation

2017 ◽  
Vol 6 (2) ◽  
pp. 50 ◽  
Author(s):  
Andreas Goette ◽  
Hein Heidbuchel ◽  
◽  
Keyword(s):  
Randomised Controlled Trials ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Rapid Onset ◽  
Practical Implementation ◽  
Controlled Trials ◽  
Efficacy And Safety ◽  
Onset Of Action ◽  
Randomised Controlled ◽  
Post Hoc

Anticoagulation is routinely prescribed to patients with persistent AF before cardioversion to reduce the risk of thromboembolic events. As direct oral anticoagulants (DOACs) have a rapid onset of action, a consistent anticoagulant effect, if taken correctly, and do not need monitoring or dose adjustments, there is considerable interest in their use for patients with AF undergoing cardioversion. Post-hoc analyses show that DOACs are safe to use prior to and following cardioversion. In addition, two randomised controlled trials, X-VeRT and ENSURE-AF, have demonstrated the efficacy and safety of the DOACs rivaroxaban and edoxaban, respectively, in this setting. The use of DOACs allows cardioversions to be performed promptly and reduces the number of cancelled procedures compared with the use of warfarin.

scholarly journals Direct Oral Anticoagulants: A Quick Guide

2017 ◽  
Vol 12 (1) ◽  
pp. 40 ◽  
Author(s):  
Julia Sikorska ◽  
James Uprichard ◽  
◽  
Keyword(s):  
Venous Thromboembolism ◽  
Vitamin K ◽  
Randomised Controlled Trials ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Controlled Trials ◽  
Major Advance ◽  
Real World Data ◽  
Randomised Controlled

Vitamin K antagonists, such as warfarin, have been the anticoagulants of choice for many years for patients with AF and other thrombotic conditions. The introduction of direct oral anticoagulants (DOACs) as alternatives represents a major advance in anticoagulation. DOACs have been found to be at least as safe and effective as vitamin K antagonists in randomised, controlled trials for stroke prevention in AF and the management of venous thromboembolism, with real-world data showing similar outcomes. With the availability of several agents, selecting the most appropriate DOAC can be challenging. The aim of the present article is to provide useful guidance on the implementation of DOAC treatment in clinical practice.

scholarly journals Direct Oral Anticoagulants for the Treatment of Acute Venous Thromboembolism Associated with Cancer: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 120 (07) ◽  
pp. 1128-1136 ◽  
Author(s):  
Michela Giustozzi ◽  
Giancarlo Agnelli ◽  
Jorge del Toro-Cervera ◽  
Frederikus A. Klok ◽  
Rachel P. Rosovsky ◽  
...  
Keyword(s):  
Major Bleeding ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Factor Xa Inhibitors ◽  
Patients With Cancer ◽  
Randomized Controlled ◽  
Recurrent Vte ◽  
Acute Venous Thromboembolism

Abstract Background International guidelines have endorsed the use of edoxaban or rivaroxaban as an alternative to low-molecular-weight heparin (LMWH) for the treatment of acute venous thromboembolism (VTE) in cancer patients. Recently, a large randomized controlled trial of apixaban versus dalteparin in patients with cancer was completed. We performed an updated meta-analysis to assess the efficacy and safety of direct oral anticoagulants (DOACs) versus LMWH in patients with cancer-associated VTE. Methods MEDLINE, EMBASE, and CENTRAL (Cochrane Controlled Trials Registry) were systematically searched up to March 30, 2020 for randomized controlled trials comparing DOACs versus LMWH for the treatment of VTE in patients with cancer. The two coprimary outcomes were recurrent VTE and major bleeding at 6 months. Data were pooled by the Mantel–Haenszel method and compared by relative risk ratios (RRs) and 95% confidence intervals (CIs). Results Four randomized controlled studies (2,894 patients) comparing apixaban, edoxaban, or rivaroxaban with dalteparin were included in the meta-analysis. Recurrent VTE occurred in 75 of 1,446 patients (5.2%) treated with oral factor Xa inhibitors and in 119 of 1,448 patients (8.2%) treated with LMWH (RR 0.62; 95% CI 0.43–0.91; I 2, 30%). Major bleeding occurred in 62 (4.3%) and 48 (3.3%) patients receiving oral factor Xa inhibitors or LMWH, respectively (RR 1.31; 95% CI 0.83–2.08; I 2, 23%). Conclusion In patients with cancer-associated VTE, oral factor Xa inhibitors reduced the risk of recurrent VTE without a significantly higher likelihood of major bleeding at 6 months compared with LMWH.

scholarly journals Efficacy and safety profile of statins in patients with cancer: a systematic review of randomised controlled trials

2020 ◽  
Vol 76 (12) ◽  
pp. 1639-1651
Author(s):  
John P. Thomas ◽  
Yoon K. Loke ◽  
Leo Alexandre
Keyword(s):  
Hepatocellular Carcinoma ◽  
Systematic Review ◽  
Statin Therapy ◽  
Safety Profile ◽  
Randomised Controlled Trials ◽  
Risk Of Bias ◽  
Controlled Trials ◽  
Efficacy And Safety ◽  
Patients With Cancer ◽  
Randomised Controlled

Abstract Purpose A growing body of preclinical and observational research suggests that statins have potential as a therapeutic strategy in patients with cancer. This systematic review of randomised controlled trials (RCTs) in patients with solid tumours aimed to determine the efficacy of statin therapy on mortality outcomes, their safety profile and the risk of bias of included studies. Methods Full-text articles comparing statin therapy versus control in solid tumours and reporting mortality outcomes were identified from Medline and Embase from conception to February 2020. A systematic review with qualitative (primarily) and quantitative synthesis was conducted. This systematic review was prospectively registered (Prospero registration CRD42018116364). Results Eleven trials of 2165 patients were included. Primary tumour sites investigated included lung, colorectal, gastro-oesophageal, pancreatic and liver. Most trials recruited patients with advanced malignancy and used sub-maximal statin doses for relatively short durations. Aside from one trial which demonstrated benefit with allocation to pravastatin 40 mg in hepatocellular carcinoma, the remaining ten trials did not demonstrate efficacy with statins. The pooled hazard ratio for all-cause mortality with allocation to pravastatin in patients with hepatocellular carcinoma in two trials was 0.69 (95% confidence interval CI 0.30–1.61). Study estimates were imprecise. There were no clinically important differences in statin-related adverse events between groups. Overall, included trials were deemed low risk of bias. Conclusion The trial evidence is not sufficiently robust to confirm or refute the efficacy and safety of statins in patients with solid malignant tumours. Study and patient characteristics may explain this uncertainty. The potential role of high-dose statins in adjuvant settings deserves further research.

Direct oral factor Xa inhibitors for the treatment of acute cancer-associated venous thromboembolism: A systematic review and network meta-analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e23156-e23156
Author(s):  
Harry E Fuentes ◽  
Robert McBane ◽  
Waldemar Wysokinski ◽  
Alfonso Javier Tafur ◽  
Charles L. Loprinzi ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Indirect Comparison ◽  
Factor Xa ◽  
Factor Xa Inhibitors ◽  
Efficacy And Safety ◽  
Patients With Cancer

e23156 Background: A direct meta-analysis was performed to explore the efficacy and safety of direct oral factor Xa inhibitors with dalteparin in patients with cancer associated acute venous thromboembolism (VTE). Also, the comparative efficacy and safety of apixaban, rivaroxaban, and edoxaban was assessed with a network meta-analysis. Methods: MEDLINE, CENTRAL, and EMBASE were searched for trials comparing direct oral anticoagulants (DOACs) to dalteparin for the management of cancer associated acute VTE. A network meta-analysis using both frequentist and Bayesian methods was performed to analyze VTE recurrence, major and clinically relevant non-major bleeding (CRNMB). Results: Three randomized control trials, at low risk of bias, enrolled 1,739 patients with cancer associated VTE. Direct comparison showed a lower rate of VTE recurrence in DOAC compared to dalteparin groups (odds Ratio [OR]:0.48, 95% Confidence interval [CI]:0.24-0.96; I2:46%). Indirect comparison suggested that apixaban had greater reduction in VTE recurrence compared to dalteparin (OR: 0.10; 95% CI: 0.01–0.82), but not rivaroxaban or edoxaban. Apixaban also had the highest probability of being ranked most effective. By direct comparisons, there was an increased likelihood of major bleeding in the DOAC group compared to dalteparin (OR: 1.70; 95% CI: 1.04–2.78). CRNMB did not differ. Indirect estimates were imprecise. Subgroup analyses in gastrointestinal cancers suggested that dalteparin may have the lowest risk of bleeding whereas estimates in urothelial cancer were imprecise. Conclusions: DOACs appear to lower the risk of VTE recurrence compared to daltaparin while increasing major bleeding. Apixaban may be associated with the lowest risk of VTE recurrence compared to the other DOACs.

Organ-specific bleeding patterns of anticoagulant therapy: lessons from clinical trials

2014 ◽  
Vol 112 (11) ◽  
pp. 918-923 ◽  
Author(s):  
Thomas Vanassche ◽  
Jack Hirsh ◽  
Jeffrey Ginsberg ◽  
John Eikelboom
Keyword(s):  
Randomised Controlled Trials ◽  
Large Scale ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
Similar Efficacy ◽  
Intestinal Bleeding ◽  
Organ Specific ◽  
Randomised Controlled ◽  
Reduced Risk

SummaryAnticoagulants are effective at preventing and treating thrombosis, but can cause bleeding. For decades, vitamin K antagonists (VKAs) have been the only available oral anticoagulants. The development of non-VKA oral anticoagulants (NOACs), which inhibit either factor Xa or thrombin stoichiometrically, has provided alternatives to VKAs for several indications. The results of recent large-scale randomised controlled trials comparing NOACs with VKAs for the prevention of stroke in patients with non-valvular atrial fibrillation (AF) have produced some unexpected results. As a group, NOACs showed similar efficacy as warfarin, but a reduced risk of major bleeding. The reduction in bleeding with NOACs was greatest with intracranial hemorrhage. In contrast, the relative risk of gastro-intestinal bleeding was increased with some NOACs. In this review, we explore the potential mechanisms as well as the implications of these organ-specific bleeding patterns.

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