Oral anticoagulant use in patients with morbid obesity: A systematic review and meta-analysis

Author(s):  
Tzu-Fei Wang ◽  
Marc Carrier ◽  
Karine Fournier ◽  
Deborah M. Siegal ◽  
Grégoire Le Gal ◽  
...  

Objectives: Obesity is associated with increased risks of atrial fibrillation (AF) and venous thromboembolism (VTE) for which anticoagulation is commonly used. However, data on the efficacy and safety of oral anticoagulants in patients with morbid obesity are limited. Methods: We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs) for AF or VTE in patients with morbid obesity. Results: We included 3 randomized controlled trials (5 studies) and 18 observational studies in adult patients with a body weight ≥ 120 kg, body mass index (BMI) ≥ 40 kg/m2 or classified as morbid obesity who received DOACs or VKAs for AF or VTE (N=77,687). The primary efficacy outcome was stroke/systemic embolism or recurrent VTE, and the primary safety outcome was major bleeding. DOACs were associated with a pooled incidence rate of stroke/systemic embolism of 1.16 per 100 person-years, compared to 1.18 with VKAs. The incidence of recurrent VTE on DOACs was 3.83 per 100 person-years, compared to 6.81 on VKAs. In both VTE and AF populations, DOACs were associated with lower risks of major bleeding compared to VKAs. However, all observational studies had moderate to serious risks of bias. Conclusions: Patients with morbid obesity on DOACs had similar risks of stroke/systemic embolism, lower rates of recurrent VTE and major bleeding events compared to those on VKAs. However, the certainty of evidence was low given that studies were mostly observational with high risk of confounding.

2021 ◽  
Author(s):  
Bo Cao ◽  
Xiaobo Hu ◽  
Min Chen ◽  
Mingfeng Shen ◽  
Lan Xu

Abstract BackgroundEvidence on the safety and effectiveness of non-vitamin K antagonist oral anticoagulants (NOACs) in atrial fibrillation (AF) patients with cancer is rather limited, so we performed this meta-analysis to compare the efficacy and safety of NOACs with vitamin K antagonists (VKAs) in real-world patients with AF and cancer. MethodsThe PubMed and Embase databases were searched up to June 2020 for eligible studies. Outputs were presented as risk ratios (RRs) and corresponding 95% confidence intervals (CIs) using a random-effects model. ResultsA total of five observational studies involving 232,234 cancer patients with AF were included. Compared with VKAs, use of NOACs was associated with decreased risks of stroke or systemic embolism (RR, 0.79; 95% CI 0.69-0.90), ischaemic stroke (RR, 0.82; 95% CI, 0.72-0.93), venous thromboembolism (VTE) (RR, 0.28; 95% CI 0.14-0.53), all-cause death (RR, 0.57; 95% CI 0.50-0.64), major bleeding (RR, 0.60; 95% CI 0.51-0.72) and intracranial or gastrointestinal bleeding (RR, 0.61; 95% CI, 0.51-0.73). In subgroup analysis, all NOACs showed similar rates of stroke or systemic embolism, ischaemic stroke but reduced rates of all-cause death, major bleeding and intracranial or gastrointestinal bleeding compared to VKAs. ConclusionsIn this combined analysis of real-world observational studies, NOACs showed lower risks of stroke or systemic embolism, ischaemic stroke, VTE, all-cause death and reduced rates of major bleeding and intracranial or gastrointestinal bleeding compared to VKAs in patients with AF and cancer.


2021 ◽  
Vol 8 ◽  
Author(s):  
Fuwei Liu ◽  
Yunyao Yang ◽  
Winglam Cheng ◽  
Jianyong Ma ◽  
Wengen Zhu

Background: Recent observational studies have compared effectiveness and safety profiles between non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in patients with atrial fibrillation (AF). Nevertheless, the confounders may exist due to the nature of clinical practice-based data, thus potentially influencing the reliability of results. This systematic review and meta-analysis were conducted to compare the effect of NOACs with warfarin based on the propensity score-based observational studies vs. randomized clinical trials (RCTs).Methods: Articles included were systematically searched from the PubMed and EMBASE databases until March 2021 to obtain relevant studies. The primary outcomes were stroke or systemic embolism (SSE) and major bleeding. Hazard ratios (HRs) and 95% confidence intervals (CIs) of the outcomes were extracted and then pooled by the random-effects model.Results: A total of 20 propensity score-based observational studies and 4 RCTs were included. Compared with warfarin, dabigatran (HR, 0.82 [95% CI, 0.71–0.96]), rivaroxaban (HR, 0.80 [95% CI, 0.75–0.85]), apixaban (HR, 0.75 [95% CI, 0.65–0.86]), and edoxaban (HR, 0.71 [95% CI, 0.60–0.83]) were associated with a reduced risk of stroke or systemic embolism, whereas dabigatran (HR, 0.76 [95% CI, 0.65–0.87]), apixaban (HR, 0.61 [95% CI, 0.56–0.67]), and edoxaban (HR, 0.58 [95% CI, 0.45–0.74]) but not rivaroxaban (HR, 0.92 [95% CI, 0.84–1.00]) were significantly associated with a decreased risk of major bleeding based on the observational studies. Furthermore, the risk of major bleeding with dabigatran 150 mg was significantly lower in observational studies than that in the RE-LY trial, whereas the pooled results of observational studies were similar to the data from the corresponding RCTs in other comparisons.Conclusion: Data from propensity score-based observational studies and NOAC trials consistently suggest that the use of four individual NOACs is non-inferior to warfarin for stroke prevention in AF patients.


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.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ruchi Desai ◽  
Gautam Krishna Koipallil ◽  
Nelson Thomas ◽  
Rahul Mhaskar ◽  
Nathan Visweshwar ◽  
...  

Abstract Direct oral anticoagulants (DOACs) may be good alternatives to low molecular weight heparin (LMWH) or vitamin K antagonists (VKA) for treatment of cancer associated thrombosis (CAT). We conducted a meta-analysis of ten randomized clinical trials to evaluate the efficacy and safety of DOACs in patients with CAT. All had study populations composed in entirety or in part of patients with CAT. The primary outcome (efficacy) was recurrent VTE and the secondary outcomes (safety outcomes) included major bleeding, clinically relevant non-major bleeding (CRNMB), and all bleeding (major bleeding + CRNMB). Participants treated with DOACs had lower risk of recurrent VTE, overall (RR 0.63; 95% CI 0.51–0.79; p < 0.0001), compared to LMWH (RR 0.57; 95% CI 0.40–0.83; p = 0.003), but not compared to VKA (RR 0.69; 95% CI 0.44–1.06; p = 0.09). Compared to LMWH, DOACs showed no difference in major bleeding risk (RR 1.31; 95% CI 0.78–2.18; p = 0.31), though had higher risk of CRNMB (RR 1.60; 95% CI 1.13–2.26; p = 0.008) and all bleeding (RR 1.49; 95% CI 1.10–2.01; p = 0.010). These results indicate that DOACs are more effective than LMWH for prevention of recurrent VTE with CAT though carry an increased risk for non-major bleeding compared to standard of care, LMWH.


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.


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.


2021 ◽  
Author(s):  
Li Jia ◽  
Mingming Zhou ◽  
Li Sun ◽  
Luhai Yu ◽  
Xiangyan He

Abstract Atrial fibrillation(AF) increases the risk of ischemic stroke and systemic embolism in patients. Moreover, Asian patients with AF are more likely to have ischemic stroke than non-Asian patients. Oral anticoagulants could effectively prevent thrombotic events. Dabigatran and Rivaroxaban are two most commonly used novel oral anticoagulants (NOACs) in Asia, but those clinicial studies in relation with them are mostly in American and European countries. Therefore, whether there are differences between Dabigatran and Rivaroxaban among Asian patients with AF in terms of efficacy and safety is still unknown. This systematic review and meta-analysis will mainly assess clinical efficacy and safety of Dabigatran versus Rivaroxaban in Asian patients with AF by a pooled analysis. We will follow the PRISMA (preferred reporting items for systematic reviews and meta-analyses) and the reporting MOOSE (Meta-analyses of Observational Studies in Epidemiology) when performing this study. Then Cochrane Library,Web of Science, PubMed and China national knowledge infrastructure will be searched for eligible retrospective investigation that report the efficacy and safety outcomes of AF patients who utilised Dabigatran or Rivaroxaban for stroke prevention in Asian countries. The abovementioned database will be comprehensively searched from inception to September 30, 2019 to locate all potentially eligible studies. Outcome measures will include safety and efficacy indicators. Safety indicators include intracranial hemorrhage, major bleeding and gastrointestinal bleeding. Efficacy indicators include systemic embolism and stroke. New evidence for clinical profile of Dabigatran versus Rivaroxaban in AF patients will be provided for decision-making of Asian patients.PROSPERO registration number: CRD42020156197


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
João Carmo ◽  
Francisco M Costa ◽  
Jorge Ferreira ◽  
Miguel Mendes

Background: In the clinical trial RE-LY, dabigatran showed a better efficacy/safety profile in comparison with warfarin, but clinical trials are few representative of the real world. We aim to access if dabigatran in real-world patients with atrial fibrillation (AF) showed a better profile in comparison with warfarin, through a systematic review and meta-analysis of observational studies comparing with vitamin K antagonists. Methods: PubMed, Embase and Scopus databases were searched through December 2014. We include observational studies comparing dabigatran to warfarin for non-valvular AF that reported clinical events during a follow-up for dabigatran 75mg, 110 mg or 150 mg, and warfarin. We proceeded to the extraction and analysis of data for clinical thromboembolic events, bleeding and mortality. Data were pooled by meta-analysis using a random-effects model. Results: We selected 9 studies involving a total of 291,703 patients, 85,399 treated with dabigatran and the remaining 206,304 with warfarin. The incidence of stroke was 1.71 / 100 patient-years for dabigatran and 2.44 / 100 patient years for warfarin (relative risk [RR] 0.91, 95% CI 0.66 to 1.27, p=0.58). The major bleeding rate was 3.90 / 100 patient-years for dabigatran and 3.92 / 100 patient years for warfarin (RR 0.90; 0.78 to 1.03, p=0.11). The all-cause mortality (RR 0.81, 0.75-0.88, p<0.001) and intracranial hemorrhage (RR 0.45, from 0.27 to 0.76, p=0.002) were significantly lower in patients treated with dabigatran in comparison to those treated with warfarin. There were no significant differences in risk of myocardial infarction (RR 0.55; 0.29 to 1.07, p=0.08), total hemorrhage (RR 1.00; 0.57 to 1.77, p=0.99), and gastro-intestinal bleeding (RR 1.14; 0.78 to 1.69, p=0.50). Conclusions: In this combined analysis of observational studies of real world, dabigatran compared to warfarin was associated with a similar risk of stroke, myocardial infarction, major bleeding, total bleeding and gastrointestinal bleeding, and a lower risk of intracranial hemorrhage and mortality.


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