3054Efficacy and safety of non-vitamin K oral anticoagulants in patients with atrial fibrillation and cancer

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
I Cavallari ◽  
G Verolino ◽  
G Patti

Abstract Background Anticoagulation in patients with cancer and atrial fibrillation (AF) is particularly challenging given the higher risk of both thrombotic and bleeding complications in this setting. Data regarding the efficacy and safety of non-vitamin K oral anticoagulants (NOACs) in AF patients with malignancy remain unclear. Purpose In the present meta-analysis we further investigate the efficacy and safety of NOACs compared to warfarin in patients with AF and cancer assuming that available studies may be individually underpowered for endpoints at low incidence, i.e. stroke, major and intracranial bleeding. Methods We performed a systematic review and meta-analysis of studies comparing the use of NOACs vs. warfarin in AF patients with cancer. Efficacy outcome measures included stroke or systemic embolism, venous thromboembolism and mortality. Safety outcome measures were major bleeding and intracranial hemorrhage. Results We pooled data from 6 identified studies enrolling a total of 31,756 AF patients with cancer. Mean follow-up was 1.7 years. Patients with cancer had significantly increased annualized rates of venous thromboembolism (1.38% vs. 0.74%), major bleeding (9.01% vs. 5.13%), in particular major gastrointestinal bleeding (2.38% vs. 1.60%), and all-cause mortality (17.73% vs. 8.50%) vs. those without (all P values <0.001), whereas the incidence of stroke or systemic embolism and intracranial hemorrhage did not differ. Compared with warfarin, treatment with NOACs nominally decreased the risk of stroke or systemic embolism (5.41% vs. 2.70%; odds ratio, OR; 95% confidence intervals, CI 0.51, 0.26–1.01; P=0.05; Figure), mainly of ischemic stroke (OR 0.56; 95% CI 0.35–0.89; P=0.01), and the risk of venous thromboembolism (OR 0.51; 95% CI 0.42–0.61; P<0.001). In cancer patients receiving NOACs there was a significant reduction of major bleeding (3.95% vs. 4.66%; OR 0.66, 95% CI 0.46–0.94; P=0.02; Figure) and intracranial hemorrhage (0.26% vs. 0.66%; OR 0.25, 95% CI 0.08–0.82; P=0.02) vs. warfarin, with no difference in gastrointestinal major bleeding rates. Conclusion AF patients on oral anticoagulation and concomitant cancer are at higher risk of venous thromboembolism, major bleeding and all-cause mortality. NOACs may represent a safer and more effective alternative to warfarin also in this setting of patients.

2019 ◽  
Vol 120 (02) ◽  
pp. 314-321 ◽  
Author(s):  
Ilaria Cavallari ◽  
Giuseppe Verolino ◽  
Silvio Romano ◽  
Giuseppe Patti

Abstract Objectives In this study-level meta-analysis, we evaluated the clinical outcome with nonvitamin K antagonist oral anticoagulants (NOACs) versus vitamin K antagonists (VKAs) in atrial fibrillation (AF) patients with cancer. Background Anticoagulation in AF patients with cancer is challenging given the coexistence of elevated thrombotic and bleeding risk. The efficacy and safety of NOACs in this setting remain unclear. Methods We included three randomized trials in our primary analysis (N = 2,661 patients) and three observational studies in our secondary, confirmatory analysis (N = 21,112 patients). Outcome measures were: the composite of any stroke or systemic embolism, ischemic stroke, venous thromboembolism, major bleeding, intracranial bleeding; and all-cause death. Mean follow-up duration was 2.2 years. Results In the primary analysis, the use of NOACs was associated with similar incidence of stroke/systemic embolism (odds ratio [OR] 0.70, 95% confidence interval 0.45–1.09; p = 0.11), ischemic stroke (OR 0.71, 0.31–1.64; p = 0.42), venous thromboembolism (OR 0.91, 0.33–2.53; p = 0.86), all-cause death (OR 1.02, 0.72–1.42; p = 0.93), and major bleeding (OR 0.81, 0.61–1.06; p = 0.13) compared with VKAs. The occurrence of intracranial bleeding was significantly lower in the NOACs versus VKAs group (OR 0.11, 0.02–0.63; p = 0.01). These results were overall confirmed in the secondary analysis, where there was additionally a significant reduction of stroke/systemic embolism, ischemic stroke, and venous thromboembolism with NOACs. Conclusion In AF patients with malignancy, NOACs appear at least as effective as VKAs in preventing thrombotic events and reduce intracranial bleeding. NOACs may represent a valid and more practical alternative to VKAs in this setting of high-risk patients.


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.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e23156-e23156
Author(s):  
Harry E Fuentes ◽  
Robert McBane ◽  
Waldemar Wysokinski ◽  
Alfonso Javier Tafur ◽  
Charles L. Loprinzi ◽  
...  

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.


Blood ◽  
2020 ◽  
Vol 136 (12) ◽  
pp. 1433-1441 ◽  
Author(s):  
Frits I. Mulder ◽  
Floris T. M. Bosch ◽  
Annie M. Young ◽  
Andrea Marshall ◽  
Robert D. McBane ◽  
...  

Abstract Direct oral anticoagulants (DOACs) are an emerging treatment option for patients with cancer and acute venous thromboembolism (VTE), but studies have reported inconsistent results. This systematic review and meta-analysis compared the efficacy and safety of DOACs and low-molecular-weight heparins (LMWHs) in these patients. MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and conference proceedings were searched to identify relevant randomized controlled trials. Additional data were obtained from the original authors to homogenize definitions for all study outcomes. The primary efficacy and safety outcomes were recurrent VTE and major bleeding, respectively. Other outcomes included the composite of recurrent VTE and major bleeding, clinically relevant nonmajor bleeding (CRNMB), and all-cause mortality. Summary relative risks (RRs) were calculated in a random effects meta-analysis. In the primary analysis comprising 2607 patients, the risk of recurrent VTE was nonsignificantly lower with DOACs than with LMWHs (RR, 0.68; 95% CI, 0.39-1.17). Conversely, the risks of major bleeding (RR, 1.36; 95% CI, 0.55-3.35) and CRNMB (RR, 1.63; 95% CI, 0.73-3.64) were nonsignificantly higher. The risk of the composite of recurrent VTE or major bleeding was nonsignificantly lower with DOACs than with LMWHs (RR, 0.86; 95% CI, 0.60-1.23). Mortality was comparable in both groups (RR, 0.96; 95% CI, 0.68-1.36). Findings were consistent during the on-treatment period and in those with incidental VTE. In conclusion, DOACs are an effective treatment option for patients with cancer and acute VTE, although caution is needed in patients at high risk of bleeding.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Norah S. Alsubaie ◽  
Shahad M. Al Rammah ◽  
Reema A. Alshouimi ◽  
Mohammed Y. Alzahrani ◽  
Majed S. Al Yami ◽  
...  

Abstract Background Venous thromboembolism (VTE) is a common complication among patients with cancer and is one of the most common causes of increased morbidity and mortality. The use of direct oral anticoagulants (DOACs) for thromboprophylaxis and treatment of cancer-associated venous thromboembolism (CA-VTE) has been evaluated in several randomized clinical trials (RCTs). The aim of this meta-analysis was to assess efficacy and safety of using DOACs for thromboprophylaxis and treatment of CA-VTE and provide a summary for available guidelines’ recommendations. Methods MEDLINE was searched to identify studies evaluating the use of DOACs for thromboprophylaxis or treatment in patients with cancer. Search was limited to peer-reviewed studies published in English. Studies were excluded if they were not RCTs or subgroup analyses of data derived from RCTs, if they did not report efficacy and safety data on patients with active cancer, or if they were published as an abstract. New VTE or VTE recurrence, and major or clinically relevant non-major bleeding (CRNMB) were used to assess the efficacy and safety, respectively. The Mantel-Haenszel random-effects model risk ratios (RRs) and the corresponding 95% confidence intervals (CIs) were calculated to estimate the pooled treatment effects of DOACs. Results Four studies evaluating DOACs use for thromboprophylaxis and four – for treatment of CA-VTE were included. Thromboprophylaxis with DOACs was associated with a significant reduction in the risk of symptomatic VTE (RR = 0.58; 95%CI 0.37,0.91) but with an incremental risk of major bleeding or CRNMB (RR = 1.57; 95%CI 1.10,2.26). CA-VTE treatment with DOACs was linked with a significant reduction in VTE recurrence (RR = 0.62; 95%CI 0.44,0.87) but with an incremental risk of CRNMB (RR = 1.58; 95%CI 1.11,2.24). Conclusions The DOACs are associated with a lower risk of symptomatic VTE and VTE recurrence, but the risk of bleeding remains a considerable concern. Clinical decisions should be made by assessing individual patient’s risk of VTE and bleeding.


2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
M Mhanna ◽  
A Beran ◽  
A Al-Abdouh ◽  
O Srour ◽  
W Abdulsattar ◽  
...  

Abstract Introduction Atrial fibrillation (AF) is the most common arrhythmia, with an estimated prevalence between 1–4%. On the other hand, obesity continued to be a prevalent health issue worldwide. Direct oral anticoagulants (DOACs) have been increasingly preferred over warfarin; however, The International Society of Thrombosis and Hemostasis (ISTH) recommended avoiding the use of DOACs in patients with a BMI &gt;40 or weight &gt;120 kg because of limited clinical data in these patients. In this meta-analysis, we aimed to evaluate the efficacy and safety of DOACs in morbidly obese patients with non-valvular AF. Method We performed a comprehensive literature search using multiple databases from database inception through January 2021, for all the studies that evaluated the efficacy and safety of DOACs in morbidly obese patients with non-valvular AF. The primary outcome of interest was stroke or systemic embolism (SSE) rate. The secondary outcome was major bleeding (MB). All meta-analyses were conducted using a random-effect model. Results A total of 10 studies including 89,494 morbidly obese patients (BMI &gt;40 or weight &gt;120 kg) with non-valvular AF on oral anticoagulation therapy (45427 on DOACs vs. 44067 on warfarin) were included in the final analysis. One included study was a randomized controlled trial (RCT), another study was a post hoc analysis of an RCT and the rest were retrospective cohort studies. The mean follow-up period was 1.8 years (range 8 months to 3.1 years). The SSE rate was significantly lower in DOACs group compared to warfarin group (odds ratio (OR): 0.71; 95% confidence interval (CI): 0.62, 0.81; p&lt;0.0001; I2=0%). MB rate was also significantly lower in DOACs group compared to the warfarin group (OR 0.60, 95% CI 0.46–0.78, P&lt;0.0001, I2=86%). Subgroup analysis in the rivaroxaban and apixaban AF cohort showed a statistically significant difference in SSE and MB event rates favoring both over warfarin therapy. Dabigatran showed non-inferiority to warfarin in SSE rate but superiority in the safety outcome. Conclusions Our meta-analysis demonstrated that DOACs are effective and safe when compared to warfarin in morbidly obese patients. However, more large scale randomized clinical trials are needed to further evaluate the efficacy and safety of DOACs compared to warfarin in this cohort of patients. FUNDunding Acknowledgement Type of funding sources: None. Stroke and systemic embolism events Major bleeding events


Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Mayumi Fukuda ◽  
Daniel E Singer ◽  
Paul A Bain ◽  
Shoichiro Sato ◽  
Daiki Kobayashi ◽  
...  

Background and purpose: Asians have higher risk of intracranial hemorrhage (ICH) compared to non-Asians. Although recent clinical trials have shown non-vitamin K antagonist oral anticoagulants (NOACs) were favorable in preventing ICH as well as thrombotic events among patients with non-valvular atrial fibrillation (NVAF), it is unclear whether the efficacy and safety of NOACs are consistent among Asians. The purpose of this study is to assess the efficacy and safety of NOACs in Asians with NVAF. Methods: PubMed, Embase, Cochrane Central, Web of Science, the Western Pacific Index Medicus, Clinicaltrials.Gov and supplemented with conference abstracts were searched up to June 2014. Phase III randomized control trials that reported efficacy and safety of NOACs vs. warfarin in Asians and non-Asians with NVAF were identified. Each study was reviewed by two reviewers and differences were resolved by consensus. The end points analyzed were all stroke or systemic embolism, ischemic and hemorrhagic stroke, major or clinically relevant non major bleeding events (CRNM), and ICH. The hazard ratio (HR) with 95% confidence interval (CI) of each endpoint in NOACs compared to warfarin was extracted separately among Asians and non-Asians. Random-effects models were used to calculate pooled HR and 95% CI. Results: 5 eligible studies were identified. Total of 8928 Asians and 64023 non-Asians were included. All stroke or systemic embolism were significantly reduced with NOACs in Asians (HR: 0.72 [95% CI: 0.59-0.88], p=0.002) but not in non-Asians (HR: 0.82 [0.66-1.01], p=0.097). The risk of ischemic stroke was not decreased in Asians (HR: 0.88 [0.64-1.21], p=0.43) or non-Asians (HR: 0.98 [0.80-1.12], p=0.73), whereas the risk of hemorrhagic stroke was significantly decreased in both groups (HR: 0.28 [0.17-0.47], p<0.001 for Asians, HR: 0.37 [0.24-0.55], p<0.001, respectively). The risk of major bleeding or CRNM was significantly reduced in Asians (HR: 0.68 [0.56-0.83], p<0.001) but not in non-Asians (HR: 0.78 [0.60-1.0], p=0.21). The risk of ICH was significantly decreased in both groups (HR: 0.30 [0.21-0.42], p<0.001, HR: 0.41 [0.34-0.48], p<0.001, respectively). Conclusions: The efficacy and safety of NOACs in Asians with NVAF is consistent with the overall results.


Author(s):  
Marco Valerio Mariani ◽  
Michele Magnocavallo ◽  
Martina Straito ◽  
Agostino Piro ◽  
Paolo Severino ◽  
...  

Abstract Background Direct oral anticoagulants (DOACs) are recommended as first-line anticoagulants in patients with atrial fibrillation (AF). However, in patients with cancer and AF the efficacy and safety of DOACs are not well established. Objective We performed a meta-analysis comparing available data regarding the efficacy and safety of DOACs vs vitamin K antagonists (VKAs) in cancer patients with non-valvular AF. Methods An online search of Pubmed and EMBASE libraries (from inception to May, 1 2020) was performed, in addition to manual screening. Nine studies were considered eligible for the meta-analysis involving 46,424 DOACs users and 182,797 VKA users. Results The use of DOACs was associated with reduced risks of systemic embolism or any stroke (RR 0.65; 95% CI 0.52–0.81; p 0.001), ischemic stroke (RR 0.84; 95% CI 0.74–0.95; p 0.007) and hemorrhagic stroke (RR 0.61; 95% CI 0.52–0.71; p 0.00001) as compared to VKA group. DOAC use was associated with significantly reduced risks of major bleeding (RR 0.68; 95% CI 0.50–0.92; p 0.01) and intracranial or gastrointestinal bleeding (RR 0.64; 95% CI 0.47–0.88; p 0.006). Compared to VKA, DOACs provided a non-statistically significant risk reduction of the outcomes major bleeding or non-major clinically relevant bleeding (RR 0.94; 95% CI 0.78–1.13; p 0.50) and any bleeding (RR 0.91; 95% CI 0.78–1.06; p 0.24). Conclusions In comparison to VKA, DOACs were associated with a significant reduction of the rates of thromboembolic events and major bleeding complications in patients with AF and cancer. Further studies are needed to confirm our results.


2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
A Wartanian ◽  
C Lewinter ◽  
R Edfors

Abstract Introduction Patients with atrial fibrillation (AF) and severe chronic kidney disease (CKD) were excluded from most phase III randomized controlled trials (RCTs) of direct oral anticoagulants (DOACs). Evidence of warfarin versus DOAC in the AF population with stage IV-V CKD is therefore limited. Aim To evaluate the effectiveness and safety of DOAC compared with warfarin on this population including dialysis patients. Methods A systematic review and meta-analysis of RCTs and observational studies involving AF patients with stage IV-V CKD treated with warfarin versus DOACs were conducted to evaluate the following outcomes: stroke (ischemic and hemorrhagic) or systemic embolism (SE), all-cause mortality, major bleeding, gastrointestinal (GI) bleeding, and intracranial bleeding. If the heterogeneity between studies was moderate to high calculated as the I2 ≥50%, a meta regression was undertaken between baseline characteristics and the study outcomes. We conducted a literature search using key words related to AF, severe CKD, DOAC and warfarin in PubMed, Embase and Cochrane Library. Results Nine studies were included in the meta-analysis. Compared to warfarin, DOAC was significantly associated with a reduced risk of stroke or systemic embolism (SE) (risk ratio [RR] = 0.69; 95% confidence interval [CI] 0.50–0.95) (Figure 1), intracranial bleeding (RR=0.54; 95% CI 0.35–0.84) and hemorrhagic stroke (RR=0.39; 95% CI 0.16–0.95). There was no significant difference between DOACs and warfarin in the risk of all-cause mortality (RR=0.80; 95% CI 0.57–1.13), major bleeding (RR = 0.70; 95% CI 0.44–1.11) (Figure 2) and GI bleeding (RR=0.76; 95% CI 0.56–1.02). For the outcome stroke or SE, dabigatran (compared with apixaban) significantly eliminated the net effect of DOAC as compared with warfarin (coefficient, 0.8; P=0.003). Regarding major bleeding, rivaroxaban and dabigatran both eliminated the DOAC effect from the meta-analysis as compared to apixaban (P=0.01 & P&lt;0.0001). Dabigatran significantly increased the risk of GI bleeding in comparison to apixaban (coefficient, 0.48; P=0.002) in comparison with the overall similar effect of warfarin in the meta-analysis. Conclusion Among patients with AF and stage IV or V CKD including dialysis patients, DOAC appears to have similar or better effectiveness and safety compared to warfarin. FUNDunding Acknowledgement Type of funding sources: None. Stroke or systemic embolism


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.


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