scholarly journals Reappraisal of Non-vitamin K Antagonist Oral Anticoagulants in Atrial Fibrillation Patients: A Systematic Review and Meta-Analysis

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.

Stroke ◽  
2021 ◽  
Author(s):  
Wengen Zhu ◽  
Zi Ye ◽  
Shilan Chen ◽  
Dexi Wu ◽  
Jiangui He ◽  
...  

Background and Purpose: Several observational studies have compared the effect of the non–vitamin K antagonist oral anticoagulants to each other in patients with atrial fibrillation. However, confounding by indication is a major problem when comparing non–vitamin K antagonist oral anticoagulant treatments in some of these studies. This meta-analysis was conducted to compare the effectiveness and safety between non–vitamin K antagonist oral anticoagulant and non–vitamin K antagonist oral anticoagulant by only including the propensity score matching studies. Methods: We systematically searched the PubMed and Ovid databases until May 2020 to identify relevant observational studies. Hazard ratios (HRs) and 95% CIs of the reported outcomes were collected and then pooled by a random-effects model complemented with an inverse variance heterogeneity or quality effects model. Results: A total of 17 retrospective cohort studies were included in this meta-analysis. Compared with dabigatran use, the use of rivaroxaban was significantly associated with increased risks of stroke or systemic embolism (HR, 1.16 [95% CI, 1.05–1.29]) and major bleeding (HR, 1.32 [95% CI, 1.24–1.41]), whereas the use of apixaban was associated with a reduced risk of major bleeding (HR, 0.78 [95% CI, 0.67–0.90]) but not stroke or systemic embolism (HR, 0.84 [95% CI, 0.56–1.28]). Compared with rivaroxaban use, the use of apixaban was associated with a decreased risk of major bleeding (HR, 0.63 [95% CI, 0.54–0.73]) but not stroke or systemic embolism (HR, 0.83 [95% CI, 0.67–1.04]). Reanalyses with the inverse variance heterogeneity or quality effects model produced similar results as the random-effects model. Conclusions: Current observational comparisons with propensity score matching methods suggest that apixaban might be a better choice compared with dabigatran or rivaroxaban for stroke prevention in atrial fibrillation patients.


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.


Stroke ◽  
2019 ◽  
Vol 50 (10) ◽  
pp. 2819-2828 ◽  
Author(s):  
Zhengbiao Xue ◽  
Hao Zhang

Background and Purpose— Several randomized trials and real-world studies have reported the efficacy and safety of non–vitamin K antagonist oral anticoagulants (NOACs) in Asian patients with atrial fibrillation; and therefore, this meta-analysis was aimed to compare the effects of NOACs with warfarin for atrial fibrillation stroke prevention in Asians. Methods— The PubMed and Embase databases were searched from January 2009 to February 2019 for studies on comparisons of NOACs versus warfarin in Asians. Risk ratios (RRs) with 95% CIs were pooled using a random-effects model. Results— Five NOAC trials and 21 observational cohorts were included. For the NOAC trials, compared with warfarin, NOACs was associated with reduced risks of stroke or systemic embolism (RR, 0.73; 95% CI, 0.59–0.90), all-cause death (RR, 0.83; 95% CI, 0.73–0.95), major bleeding (RR, 0.59; 95% CI, 0.48–0.72), and intracranial bleeding (RR, 0.36; 95% CI, 0.26–0.49). For the real-world data, compared with warfarin, NOACs was associated with decreased rates of stroke or systemic embolism (RR, 0.75; 95% CI, 0.68–0.82), ischemic stroke (RR, 0.70; 95% CI, 0.59–0.83), myocardial infarction (RR, 0.74; 95% CI, 0.58–0.93), all-cause death (RR, 0.67; 95% CI, 0.59–0.77), major bleeding (RR, 0.63; 95% CI, 0.55–0.73), intracranial bleeding (RR, 0.50; 95% CI, 0.43–0.59), and gastrointestinal bleeding (RR, 0.65; 95% CI, 0.51–0.84). The results did not change in the subgroup analyses based on the type and dose of NOACs. Conclusions— Based on published NOAC trials and real-world studies, the use of NOACs is noninferior to warfarin in Asians with atrial fibrillation irrespective of the NOAC type and dose.


Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1162-1162
Author(s):  
Desirée Campoy ◽  
Gonzalo Artaza ◽  
César A Velasquez ◽  
Tania Canals ◽  
Erik A Johansson ◽  
...  

BACKGROUND Direct oral anticoagulants (DOAC) are increasingly used in patients with Non Valvular Atrial Fibrillation (NVAF) for stroke prevention. However, Follow-Up (FU) and dosing these agents in the elderly can be challenging due to different factors, such as chronic kidney disease, frailty, falls, multifactorial anemia and concomitant polypharmacy. These factors in elderly patients predisposes to both thromboembolic and bleeding events once atrial fibrillation occurs. Therefore, balancing risks and benefits of antithrombotic strategies in older populations is crucial. Despite recent increases in DOAC use in NVAF, there are still limited data regarding DOACs effectiveness and safety in frail elderly patients. AIM To assess the effectiveness and safety according to DOAC or Vitamin K Antagonist (VKA) in a cohort of elderly patients with NVAF. METHODS From April 2016 to April 2019, we consecutively included NVAF elderly patients (≥80 years-old) treated with DOAC or VKA in a prospective multicenter registry. Demographic, laboratory, frailty risk stratification and antithrombotic therapy data were collected. Patients had a minimum FU of 6 months. VKA patients had a standard FU through digital international normalized ratio (INR) control and the efficacy of therapy was determined by the time in therapeutic range (TTR) values from the preceding 6 months of treatment using Rosendaal's method. FU in DOAC patients was performed through structured and integral assessment following the Tromboc@t Working Group recommendations for management in patients receiving DOAC (Olivera et al, Med Clin 2018). Key practical management aspects are listed in the flow chart (Figure 1). Clinical Frailty Scale (CFS score) was assigned to each patient at the beginning and during the FU; patients were classified into three categories: non-frail (CFS 1-4), mild-to-moderately frail (CFS 5-6), and severely frail (CFS 7-9). RESULTS From a total of 1040 NVAF patients, 690 (63.5%) were treated with DOAC (61 dabigatran, 95 rivaroxaban, 254 edoxaban and 280 apixaban) and 350 with VKA. In the VKA group, the mean TTR was 52.8%. Demographic characteristics and CFS score are summarized in table 1. Kaplan-Meier analysis (median FU: 16.5 months) showed a significantly high incidence of stroke/systemic embolism among VKA patients vs DOAC patients (4.2 vs 0.5 events per 100 patient-years, p<0.001). Major bleeding in the DOAC group was significantly infrequent compared with VKA group (2.2 vs 8.9 events, p=0.001). In the DOAC group, 90% (n=20/22) of the major bleedings were gastrointestinal [16 rivaroxaban and 4 edoxaban]. However, in the VKA group 64% (n = 20/31) were gastrointestinal, 25.8% (n= 8/31) intracranial and 9.7% (n = 3/31) urogenital bleedings. We identified 365 very elderly patients (aged ≥ 90 years) of which 270 (39.1%) were DOAC patients and 95 (27.1%) VKA patients. In this subgroup of patients, after a multivariate regression analysis, the stroke/systemic embolism incidence was similar in both treatment groups regardless of the age, but major bleeding decreased significantly in DOAC group (adjusted HR 0.247, 95% CI 0.091-0.664). CONCLUSIONS Our data indicate that DOACs can be a good therapeutic option for stroke/systemic embolism prevention in frail elderly patients, showing low rates of stroke as well as bleeding events when a structured and integral FU is applied to anticoagulated patients. Further investigations are necessary to analyze the impact in the quality of life and net clinical benefit of anticoagulant therapy when a FU program is applied in elderly patients. Disclosures Sierra: Novartis: Honoraria, Research Funding, Speakers Bureau; Astellas: Honoraria; Pfizer: Honoraria; Daiichi-Sankyo: Honoraria, Speakers Bureau; Abbvie: Honoraria, Speakers Bureau; Roche: Honoraria; Jazz Pharmaceuticals: Honoraria.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Mahmoud El Iskandarani ◽  
Islam Shatla ◽  
Muhammad Khalid ◽  
Bara El Kurdi ◽  
Timir Paul ◽  
...  

Background: Current guidelines recommend against the use of direct oral anticoagulation (DOAC) therapy in patients with atrial fibrillation (AF) in the setting of significant liver disease (LD) due to lack of evidence in safety and efficacy studies. However, recently studies have investigated the role of DOAC in comparison to Vitamin K antagonist (VKA) in this category of patients. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of this approach. Hypothesis: DOAC is safe and effective compared to VKA in AF with LD patients. Method: Unrestricted search of the PubMed, EMBASE, and Cochrane databases performed from inception until June 1, 2020 for studies comparing DOAC with VKA including more than 100 AF patients with LD. Relevant data were extracted and analyzed using Revman 5.3 software. Hazard ratio (HR) and 95% Confidence interval (CI) were calculated using the random-effects model. Result: A total of 5 studies (3 retrospective and 2 post hoc analysis) were included examining 39,064 patients with AF and LD (25,398 DOAC vs 13,669 VKA). DOAC is associated with lower risk of major bleeding compared to VKA with a HR of 0.68 (95% CI 0.47-0.98; I 2 =53%), all-cause mortality (HR 0.74;95% CI 0.59-0.94; I 2 =61%), and intracranial bleeding (HR 0.48; 95% CI 0.40-0.58; I 2 =0). There was no significant difference in ischemic stroke risk (HR 0.73; 95% CI 0.47-1.14; I 2 =72%) and gastrointestinal bleeding risk (0.96; 95% CI 0.61-1.51; I 2 =41%) between DOAC and VKA. Conclusion: DOAC is non-inferior to VKA regarding ischemic stroke prevention in AF patients with LD. Moreover, DOAC is associated with a lower risk of major bleeding, intracranial bleeding and all-cause mortality. Further randomized trials are needed to validate our findings.


Stroke ◽  
2019 ◽  
Vol 50 (8) ◽  
pp. 2125-2132
Author(s):  
Leonardo Knijnik ◽  
Manuel Rivera ◽  
Vanessa Blumer ◽  
Rhanderson Cardoso ◽  
Amanda Fernandes ◽  
...  

Background and Purpose— The optimal antithrombotic strategy to balance thromboembolic and bleeding events, especially acute stroke, for patients with atrial fibrillation following coronary stenting remains a matter of debate. We conducted a network meta-analysis to identify the antithrombotic regimen associated with the lowest rate of bleeding and thromboembolic events in atrial fibrillation after coronary stenting. Methods— PubMed, Scopus, and Cochrane Central were searched for randomized controlled trials and observational studies of patients with atrial fibrillation after coronary stenting. The outcomes of interest were stroke, myocardial infarction, major adverse cardiac events, mortality, and major bleeding. A network meta-analysis was performed comparing the available antithrombotic regimens in the literature. Results— Three randomized and 15 observational studies were included, with a total of 23 478 participants. Median follow-up was 2 years. Network meta-analysis demonstrated that vitamin K antagonist plus single antiplatelet therapy or direct-acting oral anticoagulant plus single antiplatelet therapy were the most effective regimens in preventing stroke. Direct-acting oral anticoagulant regimens were associated with lower major bleeding rates than vitamin K antagonist regimens. Regimens with dual antiplatelet therapy were associated with lower rates of myocardial infarction. Vitamin K antagonist plus dual antiplatelet therapy was associated with a lower mortality and low-dose direct-acting oral anticoagulants with decreased major cardiovascular adverse events. Conclusions— Direct-acting oral anticoagulant regimens were associated with less major bleeding and major cardiovascular adverse events, but vitamin K antagonists were associated with decreased mortality and stroke. These results suggest that the decision of antithrombotic therapy in patients with atrial fibrillation after percutaneous coronary intervention needs to be individualized.


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