Anticoagulant and Antiplatelet therapy for the prevention of stroke in AF with arterial origin stroke: a meta-analysis.

2019 ◽  
Author(s):  
Mingxia Li ◽  
Hong Lin ◽  
Jiankuan Shi ◽  
Qianru Yang ◽  
Jianjun Li ◽  
...  
Keyword(s):  
Antiplatelet Therapy ◽  
Major Bleeding ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Cochrane Library ◽  
Stroke Recurrence ◽  
Efficacy And Safety ◽  
Systemic Embolism ◽  
Risk Of Bleeding

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.

Comparative Efficacy and Safety of Duration of Dual Antiplatelet Therapy in Patients with CAD Undergoing Drug-eluting Stent Implantation: A Systematic Review and Network Meta-analysis

2020 ◽  
Vol 26 (44) ◽  
pp. 5739-5745
Author(s):  
Jieqiong Guan ◽  
Wenjing Song ◽  
Pan He ◽  
Siyu Fan ◽  
Hong Zhi ◽  
...  
Keyword(s):  
Antiplatelet Therapy ◽  
Major Bleeding ◽  
Dual Antiplatelet Therapy ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Drug Eluting Stent ◽  
Efficacy And Safety ◽  
Risk Of Bleeding ◽  
Increased Risk ◽  
Drug Eluting

Objective: The aim was to evaluate the efficacy and safety of duration of dual antiplatelet therapy (DAPT) for patients who received percutaneous coronary intervention (PCI) with a drug-eluting stent. Background: The optimal duration of DAPT to balance the risk of ischemia and bleeding in CAD patients undergoing drug-eluting stent (DES) implantation remains controversial. Methods: PubMed, Cochrane Library, Web of Science, Clinicaltrials.gov, CNKI and Wanfang Databases were searched for randomized controlled trials of comparing different durations of DAPT after DES implantation. Primary outcomes were major adverse cardiac and cerebrovascular events (MACCE), and major bleeding, and were pooled by Bayes network meta-analysis. Net adverse clinical and cerebral events were used to estimate the surface under the cumulative ranking (SUCRA) curves. The subgroup analysis based on clinical status, follow-up and area was conducted using traditional pairwise meta-analysis. Results: A total of nineteen trials (n=51,035) were included, involving six duration strategies. The network metaanalysis showed that T2 (<6-month DAPT followed by aspirin, HR:1.51, 95%CI:1.02-2.22), T3 (standard 6-month DAPT, HR:1.47, 95%CI:1.14-1.91), T4 (standard 12-month DAPT, HR:1.41, 95%CI:1.15-1.75) and T5 (18-24 months DAPT, HR:1.47, 95%CI:1.09-1.97) was associated with significantly increased risk of MACCE compared to T6 (>24-month DAPT). However, no significant difference was found in MACCE risk between T1 (<6-month DAPT followed by P2Y12 monotherapy) and T6. Moreover, T5 was associated with significantly increased risk of bleeding compared to T1(RR:3.94, 95%CI:1.66-10.60), T2(RR:3.65, 95%CI:1.32-9.97), T3(RR:1.93, 95%CI:1.21-3.50) and T4(RR:1.89, 95%CI:1.15-3.30). The cumulative probabilities showed that T6(85.0%), T1(78.3%) and T4(44.5%) were the most efficacious treatment compared to the other durations. In the ACS (<50%) subgroup, T1 was observed to significantly reduce the risk of major bleeding compared to T4, but not in the ACS (≥50%) subgroup. Conclusions: Compared with other durations, short DAPT followed by P2Y12 inhibitor monotherapy showed non-inferiority, with a lower risk of bleeding and not associated with an increased MACCE. In addition, the risk of major bleeding increased significantly, starting with DAPT for 18-month. Compared with the short-term treatment, patients with ACS with the standard 12-month treatment have a better prognosis, including lower bleeding rate and the decreased risk of MACCE. Due to study's limitations, the results should be verified in different risk populations.

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&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

scholarly journals Efficacy and safety of direct oral anticoagulants in morbidly obese patients with non-valvular atrial fibrillation: a systematic review and meta-analysis

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
M Mhanna ◽  
A Beran ◽  
A Al-Abdouh ◽  
O Srour ◽  
W Abdulsattar ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Major Bleeding ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Morbidly Obese ◽  
Obese Patients ◽  
Efficacy And Safety ◽  
Systemic Embolism ◽  
Warfarin Group

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

scholarly journals Bleeding Risk in Non-Valvular Atrial Fibrillation Patients Receiving Direct Oral Anticoagulants and Warfarin: A Systematic Review and Meta-Analysis of Observational Studies

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3672-3672 ◽  
Author(s):  
Yimin Pearl Wang ◽  
Rohan Kehar ◽  
Alla Iansavitchene ◽  
Alejandro Lazo-Langner
Keyword(s):  
Major Bleeding ◽  
Lower Risk ◽  
Observational Studies ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Bleeding Risk ◽  
Risk Of Bleeding ◽  
Significant Difference

Introduction: The standard oral anticoagulant therapy administered to non-valvular AF patients has typically been Vitamin K Antagonists (VKA) particularly warfarin. In recent years, Direct Oral Anticoagulants (DOACs) including Direct Thrombin Inhibitors (DTI) and Direct Factor Xa inhibitors (FXa inhibitors) have become an alternative to warfarin. Randomized trials comparing warfarin and DOACs showed comparable effectiveness without significant additional major bleeding risk. However, bleeding events in RCTs may differ from those in daily use due to the routine exclusion of patients with a higher risk of bleeding from many studies. We aimed to assess bleeding risk between DOACs and warfarin in AF patients in observational studies and we also sought to determine differences between patients that were experienced or naïve to oral anticoagulants. Methods: A systematic literature search was conducted in the OVID MEDLINE® and EMBASE® electronic databases. Observational studies and randomized control trials (RCT) from 1990 to January 2019 were retrieved and examined by two independent reviewers. A pooled effect hazard ratio (HR) was calculated using a random effects model using the generic inverse variance method. Subgroup analyses according to previous exposure to anticoagulants, study type, funding type and DOAC type were conducted. The primary outcome was major bleeding risk. The secondary outcome was clinically relevant non-major bleeding. All studies must have used an established or validated definition of major bleeding. Results: The initial literature search identified 3359 potentially eligible citations. After primary screening, 150 articles were eligible for full text review and there were 35 studies including 2,356,201 patients that met the inclusion criteria. Overall, patients on DOACs were less likely to experience a bleeding event compared to warfarin (HR 0.78, 95%CI 0.71, 0.85, P&lt;0.001). The results were consistent when analyzing patients receiving DTIs or FXa inhibitors (DTI: HR 0.76, 95% CI 0.67,0.87; FXa inhibitors: HR 0.79, 95% CI 0.69,0.89). However, among patients receiving factor Xa inhibitors, there was a significant difference in the risk of bleeding according to individual drug. Among patients receiving rivaroxaban the risk of bleeding was similar to warfarin (HR 0.98, 95%CI 0.91,1.06, p=0.60) whereas in those receiving apixaban there was a 40% reduction in the risk of bleeding compared to warfarin (HR 0.60, 95%CI 0.50,0.71, p&lt;0.001) (Figure 1). Three studies reported information according to previous anticoagulant exposure. The overall pooled hazard ratio was 0.68 (95% CI 0.55, 0.82 p&lt;0.001) in favor of patients on DOACs. In the subgroup analysis of previous anticoagulant use, the risk of bleeding was lower for DOACs compared to warfarin in both the experienced population (HR 0.70, 95%CI 0.51, 0.96) and the naïve population (HR 0.64, 95% CI 0.47,0.87). However, heterogeneity was moderate to high among both subgroups. Conclusion: This review and meta-analysis of observational studies including over 2.3 million patients showed that overall DOACs have a lower risk of major bleeding and clinically relevant non-major bleeding compared to warfarin. Most importantly, although the pooled effect estimate did not differ between DTIs and FXa inhibitors, among patients receiving FXa inhibitors there was a significant difference between individual agents. Patients on apixaban had a significantly lower risk of bleeding compared to warfarin in contrast to patients on rivaroxaban who had a similar risk. Disclosures No relevant conflicts of interest to declare.

scholarly journals Direct oral anticoagulants versus vitamin K antagonists in patients with atrial fibrillation and cancer a meta-analysis

2020 ◽  
Author(s):  
Marco Valerio Mariani ◽  
Michele Magnocavallo ◽  
Martina Straito ◽  
Agostino Piro ◽  
Paolo Severino ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Major Bleeding ◽  
Meta Analysis ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Significant Risk ◽  
Bleeding Complications ◽  
Efficacy And Safety

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.

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
Keyword(s):  
Atrial Fibrillation ◽  
Venous Thromboembolism ◽  
Intracranial Hemorrhage ◽  
Major Bleeding ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Efficacy And Safety ◽  
Systemic Embolism ◽  
Patients With Cancer ◽  
All Cause Mortality

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.

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.

scholarly journals Efficacy and safety of Dabigatran vs. Rivaroxaban among Asians with non-valvular atrial fibrillation：Protocol for a systematic review and meta-analysis

2021 ◽  
Author(s):  
Li Jia ◽  
Mingming Zhou ◽  
Li Sun ◽  
Luhai Yu ◽  
Xiangyan He
Keyword(s):  
Systematic Review ◽  
Ischemic Stroke ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Cochrane Library ◽  
Efficacy And Safety ◽  
Systemic Embolism ◽  
China National Knowledge Infrastructure ◽  
Asian Patients ◽  
Meta Analyses

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

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

2021 ◽  
Author(s):  
Tzu-Fei Wang ◽  
Marc Carrier ◽  
Karine Fournier ◽  
Deborah M. Siegal ◽  
Grégoire Le Gal ◽  
...  
Keyword(s):  
Systematic Review ◽  
Morbid Obesity ◽  
Major Bleeding ◽  
Observational Studies ◽  
Meta Analysis ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Efficacy And Safety ◽  
Systemic Embolism ◽  
Recurrent Vte

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.

Direct Oral Anticoagulants versus Warfarin in Patients with Atrial Fibrillation: Patient-Level Network Meta-Analyses of Randomized Clinical Trials with Interaction Testing by Age and Sex

Circulation ◽  
2022 ◽  
Author(s):  
Anthony P. Carnicelli ◽  
Hwanhee Hong ◽  
Stuart J. Connolly ◽  
John Eikelboom ◽  
Robert P. Giugliano ◽  
...  
Keyword(s):  
Major Bleeding ◽  
Individual Patient Data ◽  
Standard Dose ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Efficacy And Safety ◽  
Systemic Embolism ◽  
Continuous Covariate ◽  
Meta Analyses ◽  
Lower Hazard

Background: Direct oral anticoagulants (DOACs) are preferred over warfarin for stroke prevention in atrial fibrillation (AF). Meta-analyses using individual patient data offer significant advantages over study-level data. Methods: We used individual patient data from the COMBINE AF database, which includes all patients randomized in the 4 pivotal trials of DOACs vs warfarin in AF (RE-LY, ROCKET AF, ARISTOTLE, ENGAGE AF-TIMI 48), to perform network meta-analyses using a stratified Cox model with random effects comparing standard-dose DOAC, lower-dose DOAC, and warfarin. Hazard ratios (95% CIs) were calculated for efficacy and safety outcomes. Covariate-by-treatment interaction was estimated for categorical covariates and for age as a continuous covariate, stratified by sex. Results: A total of 71,683 patients were included (29,362 on standard-dose DOAC, 13,049 on lower-dose DOAC, 29,272 on warfarin). Compared with warfarin, standard-dose DOACs were associated with a significantly lower hazard of stroke/systemic embolism (883/29312 [3.01%] vs 1080/29229 [3.69%]; HR 0.81, 95% CI 0.74-0.89), death (2276/29312 [7.76%] vs 2460/29229 [8.42%]; HR 0.92, 95% CI 0.87-0.97) and intracranial bleeding (184/29270 [0.63%] vs 409/29187 [1.40%]; HR 0.45, 95% CI 0.37-0.56), but no statistically different hazard of major bleeding (1479/29270 [5.05%] vs 1733/29187 [5.94%]; HR 0.86, 95% CI 0.74-1.01), whereas lower-dose DOACs were associated with no statistically different hazard of stroke/systemic embolism (531/13049 [3.96%] vs 1080/29229 [3.69%]; HR 1.06, 95% CI 0.95-1.19) but a lower hazard of intracranial bleeding (55/12985 [0.42%] vs 409/29187 [1.40%]; HR 0.28, 95% CI 0.21-0.37), death (1082/13049 [8.29%] vs 2460/29229 [8.42%]; HR 0.90, 95% CI 0.83-0.97), and major bleeding (564/12985 [4.34%] vs 1733/29187 [5.94%]; HR 0.63, 95% CI 0.45-0.88). Treatment effects for standard- and lower-dose DOACs versus warfarin were consistent across age and sex for stroke/systemic embolism and death, whereas standard-dose DOACs were favored in patients with no history of vitamin K antagonist use (p=0.01) and lower creatinine clearance (p=0.09). For major bleeding, standard-dose DOACs were favored in patients with lower body weight (p=0.02). In the continuous covariate analysis, younger patients derived greater benefits from standard-dose (interaction p=0.02) and lower-dose DOACs (interaction p=0.01) versus warfarin. Conclusions: Compared with warfarin, DOACs have more favorable efficacy and safety profiles among patients with AF.

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