scholarly journals Bleeding risks with novel oral anticoagulants especially rivaroxaban versus aspirin: a meta-analysis

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Xiehui Chen ◽  
Weichao Huang ◽  
Aimei Sun ◽  
Lili Wang ◽  
Fanrui Mo ◽  
...  

Abstract Background This pairwise meta-analysis determines the difference in bleeding risks associated with the use of novel oral anticoagulants (NOACs) and aspirin. Methods PubMed, the Cochrane Library database, clinicaltrial.gov, and related studies were searched for randomized control trials (RCTs) comparing NOAC and aspirin published between January 1, 2000 and May 10, 2021. The primary endpoint was intracranial hemorrhage (ICH). Results Eleven studies involving 57,645 patients were included. Compared to aspirin, rivaroxaban (5 mg/day) had a similar risk of ICH, major bleeding, and fatal bleeding; rivaroxaban (10 mg/day) had higher risks of gastrointestinal hemorrhage (OR: 1.41; 95% CI: 1.03–1.94; P = 0.032; I2 = 0%) and a similar risk of ICH, major bleeding, and fatal bleeding; and rivaroxaban (15–20 mg/day) had higher risks of ICH (OR: 3.21; 95% CI: 1.36–7.60; P = 0.008; I2 = 0%), major bleeding (OR: 2.64; 95% CI: 1.68–4.16; P < 0.001; I2 = 0%), and fatal bleeding (OR: 2.26; 95% CI: 1.25–4.08; P = 0.007; I2 = 0%) and a similar risk of gastrointestinal hemorrhage. Bleeding outcomes between other NOACs (apixaban and dabigatran etexilate) and aspirin were not different. Conclusions The bleeding risks associated with NOACs depend on drug type and dosage. For ≥15 mg/day of rivaroxaban, the risk of ICH was significantly higher than that with aspirin. However, further studies comparing dabigatran etexilate and apixaban versus aspirin are warranted to draw a definite conclusion.

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Sunil Upadhaya ◽  
Seetharamprasad Madala ◽  
Sunil Badami

Introduction: Patients with cancer are at high risk for recurrent thromboembolic phenomenon. Use of novel oral anticoagulants (NOAC) for treatment of venous thromboembolism (VTE) in such patients is controversial. We conducted this updated meta-analysis to evaluate the pooled efficacy and safety of NOAC in patients with cancer. Methods: We did systematic search of PubMed and Cochrane library databases for randomized controlled trials comparing NOAC with low molecular weight heparin (LMWH) for VTE treatment in cancer patients till April 2020. The efficacy outcomes were recurrent VTE and all-cause mortality rates, and the primary safety outcome was incidence of major bleeding rate. Results: Four randomized controlled studies comparing NOAC with LMWH (1446 patients in NOAC group and 1448 patients in LMWH group) were included in our study. Use of NOAC lead to significant reduction in recurrent VTE rate (odds ratio (OR): 0.55 [0.36-0.84], I 2 = 45 %, p value = 0.006) (Figure 1). However, we did not find any significant difference in rate of major bleeding (OR: 1.30 [0.76-2.23], I 2 = 35%, p value = 0.34) (Figure 2) and all-cause mortality (OR: 1 [0.80 - 1.26], I 2 = 33%, p value = 0.98). Conclusions: This updated meta-analysis showed comparatively lower pooled recurrent VTE rate in patient being treated with NOAC, whereas similar rates of major bleeding and all-cause death. NOAC are more efficacious and has similar safety profile compared with LMWH.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
R Sakurai

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&lt;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


2019 ◽  
Author(s):  
Mingxia Li ◽  
Hong Lin ◽  
Jiankuan Shi ◽  
Qianru Yang ◽  
Jianjun Li ◽  
...  

Abstract Background Anticoagulation and antiplatelet therapy were adopted respectively for the prevention ofcardio-embolic stroke or arterial origin stroke. while it’s difficult to make decisions for individual with Atrial fibrillation(AF)and arterial origin stroke as comorbidities, so we attempted to evaluate the efficacy and safety ofanticoagulants and antiplatelet forthe prevention of stroke in AF with arterial origin stroke and make an optimal treatment for these comorbidities. Methods Databases included PubMed, Cochrane Library and ClinicalTrials.gov were searched up to 31 Aug 2019. Eight RCTs with 77048 participants were enrolled. Results Direct oral anticoagulants(DOACs) reduced the relative risk of stroke and systemic embolism by 15% (95%CI 0.75-0.97, I2=65.6%) and the major bleeding by 23%(95%CI 0.63-0.95, I2=92.3%,). DOACs or warfarin plus aspirin compared with DOACs or warfarin alone did not show the benefit on stroke and systemic embolism prevent in AF patients, but increase the risk of major bleeding with RR 1.40 (95%CI 1.13-1.75,) and 1.33(95%CI 1.09-1.63)respectively. No differences in preventionof ischemic stroke were detected between OACs versus aspirin in arterial origin stroke. The major bleeding was significantly higher in the OACs group (RR,2.40,1.46-3.94, I2=62.2%). However, compared with aspirin, rivaroxabandid not increase the risk of major bleeding in Branch atheromatous stroke (RR,1.54,95%CI 0.26-9.12). Conclusions We speculatedthat DOACs alone may be enough to prevent stroke recurrence and not to increase the risk of bleeding in AF patients with arterial origin stroke. The well designed RCTs with the direct comparison would be needed in future.


2018 ◽  
Vol 13 (3) ◽  
pp. 273
Author(s):  
Maodi Xu ◽  
Qingquan Xue ◽  
Zhichen Pu ◽  
Zijing Wu ◽  
Haitang Xie

<p>The aim of this meta-analysis was to systematically evaluate the efficacy and safety of novel oral anticoagulants and vitamin K antagonists in the treatment of venous thromboembolism. A total of 6 studies met the inclusion criteria and a total of 19,350 patients with venous thromboembolism were included. Among them, rivaroxaban (3 RCTs, n=90/3,449/4,832); dabigatran (2 RCTs, n=200/2,539); edoxaban (1 RCT, n=8,240). The results of meta-analysis showed that the total bleeding rate after treatment with the vitamin K antagonist group was higher than with the new oral anticoagulant group (OR=0.82, 95% confidence interval 0.75-0.90, p&lt;0.0001), and the difference was highly statistically significant. Overall, new oral anticoagulants are compara-ble to vitamin K antagonists, but new oral anticoagulants can reduce the occurrence of bleeding events and the safety was superior to vitamin K antagonists.</p>


Vascular ◽  
2021 ◽  
pp. 170853812110027
Author(s):  
Gustavo Muçouçah Sampaio Brandão ◽  
Rafael D Malgor ◽  
Tarsila Vieceli ◽  
Raissa Carolina Fonseca Cândido ◽  
José Francisco Secorun Inácio ◽  
...  

Introduction Treatment of cancer-associated venous thromboembolism (CAVTE) remains challenging. The aim of this study was to assess the outcomes of direct acting oral anticoagulants (DOAs) for the treatment of CAVTE. Materials and methods A network meta-analysis of randomized clinical trials comparing DOAs (Apixaban, Rivaroxaban, and Edoxaban) versus Dalteparin for the treatment of CAVTE was performed. Outcomes of interest included, VTE recurrence, all-cause mortality, event-free survival, major bleeding, and clinically relevant non-major bleeding (CRNMB). Analysis was based on a random effects model and Bayesian Markov-chain Monte Carlo method was used for indirect comparisons. Results Four RCTs involving 2894 patients were included. Overall certainty of evidence was moderate regarding all outcomes. DOAs exhibited lower risk of VTE (RR 0.62; 95% CI 0.44, 0.87; P = 0.007), similar risk of major bleeding (RR 1.33; 95% CI 0.84, 2.11; P = 0.23), and higher risk of CRNMB (RR 1.66, 95% CI 1.08, 2.56; P = 0.02), compared with Dalteparin. Risk of all-cause mortality and event-free survival were similar between groups with RR 0.99 (95% CI 0.84, 1.16) and RR 1.03 (95% CI 0.94, 1.13), respectively. Apixaban ranked first for recurrent VTE (42.4%) and major bleeding (62.3%) and Dalteparin ranked first for CRNMB (54.7%). Rivaroxaban ranked best considering all-cause mortality (58.7%); Apixaban ranked best for event-free survival (83.6%). Conclusions DOAs presented a reduced risk of recurrent VTE with similar risk of major bleeding compared to Dalteparin. However, a higher risk of CRNMB is expected when this cohort of patients are treated with DOAs instead of Dalteparin.


Blood ◽  
2014 ◽  
Vol 124 (15) ◽  
pp. 2450-2458 ◽  
Author(s):  
Chatree Chai-Adisaksopha ◽  
Mark Crowther ◽  
Tetsuya Isayama ◽  
Wendy Lim

Key Points TSOACs are associated with less major bleeding, fatal bleeding, clinically relevant nonmajor bleeding, and total bleeding. The meta-analysis does not show increased risk of major gastrointestinal bleeding in patients who received TSOACs compared with warfarin.


2021 ◽  
Vol 12 ◽  
Author(s):  
Nan-Nan Shen ◽  
Chi Zhang ◽  
Na Wang ◽  
Jia-Liang Wang ◽  
Zhi-Chun Gu ◽  
...  

Background: In routine clinical practice, non-standard doses of direct oral anticoagulants (DOACs) are commonly used in patients with atrial fibrillation (AF). However, data on the clinical outcomes of non-standard doses of DOACs are limited.Methods: The MEDLINE, Embase, and Cochrane Library databases were systematically searched from their inception until 30 June 2020 for studies that reported the effectiveness or safety outcomes of non-standard doses of DOACs compared with on-label doses of DOACs in patients with atrial fibrillation. Non-standard doses of DOACs were defined as under or over-dose of DOACs based on the recommended standard doses in drug labels. A random-effects meta-analysis was performed to calculate the pooled hazard ratio and associated 95% confidence interval (95% confidence interval). Subgroup analyses were conducted according to individual DOACs and different geographic regions.Results: Ten articles involving 148,909 patients with AF were included. There were no significant differences between under-dosing and on-label dosing with respect to stroke/systematic embolism (HR: 1.01, 95% CI: 0.93–1.09), major bleeding (HR: 0.98, 95% CI: 0.77–1.19), intracranial haemorrhage (HR: 1.07, 95% CI: 0.74–1.40), gastrointestinal bleeding (HR: 1.10, 95% CI: 0.82–1.39), and myocardial infarction (HR: 1.07, 95% CI: 0.89–1.25), except for an increased risk of death (HR: 1.37, 95% CI: 1.01–1.73). We observed a significant association between over-dosing of DOACs and increased risk of stroke/systematic embolism (HR: 1.18, 95% CI: 1.04–1.32), major bleeding (HR: 1.16, 95% CI: 1.03–1.29), and death (HR: 1.21, 95% CI: 1.03–1.38) compared with on-label dosing. Furthermore, over-dosing of DOACs increased the risk of stroke/systematic embolism (HR: 1.16; 95% CI: 1.00–1.33) and major bleeding events (HR: 1.18; 95% CI: 1.00–1.37) in Asian patients.Conclusion: A reduced dose of DOACs might be safely and effectively used in clinical practice, especially in Asian patients, whereas high-dose DOACs might not be well tolerated by Asian patients.


2020 ◽  
pp. 1-7 ◽  
Author(s):  
Maryam Saleem ◽  
Maryam Saleem ◽  
Mohammed Osman ◽  
Saira Farid ◽  
Christopher M. Bianco ◽  
...  

There is uncertainty about the choice of anticoagulation therapy in patients with malignancy and venous thromboembolism (VTE). While low-molecular weight heparin (LMWH) remains the current standard, direct oral anticoagulants (DOACs) have emerged as an appealing alternative option. The primary objective of this analysis was to compare the efficacy and safety of DOACs versus LMWH in patients with malignancy and VTE. The secondary objective was to compare the safety and efficacy of the different DOACs. An online search of PubMed, EMBASE, the Cochrane Library and ClinicalTrials.gov from inception until April 2020 was conducted. Four RCTs encompassing 2,907 patients, (50.5% men and mean age of 65.7 ± 10.5) were selected. At a mean follow up of 12 months, moderate certainty evidence showed no differences between DOAC and LMWH in VTE recurrence (HR, 0.54 [CI 0.23 to 1.28], I2 = 56%, p=0.23), in major bleeding (HR, 1.38 [CI 0.45 to 4.22], I2 = 33%, p=0.21) or clinically relevant non-major bleeding (CRNMB) (HR, 1.77 [CI 0.49 to 6.40], I2 = 73.9%, p=0.087). There was no difference between the DOACs when compared to each other. In conclusion, DOACs are an acceptable alternative to LMWHs for the treatment of VTE in patients with malignancy.


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