Direct Acting Oral Anticoagulant vs. Warfarin in the Prevention of Thromboembolism in Patients With Non-valvular Atrial Fibrillation With Valvular Heart Disease—A Systematic Review and Meta-Analysis

Purpose: There is uncertainty as to which anticoagulant should be used in non-valvular atrial fibrillation (AF) with valvular heart disease. This systematic review and meta-analysis aimed to assess the efficacy and safety of direct-acting oral anticoagulants (DOACs) compared with warfarin in patients with non-valvular AF with valvular heart disease.Methods: We performed a comprehensive literature search using PubMed, Scopus, Embase, and Clinicaltrials.gov from the inception of databases up until August 2, 2021, and the search was updated and finalized on October 17, 2021. The intervention group was DOACs and the control group was warfarin. The primary outcome was systemic embolism and stroke (SSE), and the secondary outcome was major bleeding and intracranial hemorrhage. The pooled effect estimate was reported as the hazard ratio (HR) and odds ratio (OR).Results: There were 21,185 patients from seven studies included in this systematic review and meta-analysis. Stroke and systemic embolism were lower in patients receiving DOACs [HR 0.76 (95% CI 0.67, 0.87), p < 0.001; I2: 5%] compared with warfarin. The subgroup analysis on RCTs showed the significant reduction of SSE in the DOACs group [HR 0.73 (95% CI 0.60, 0.89), p = 0.002; I2: 16%]. There was no significant difference in terms of major bleeding [HR 0.89 (95% CI 0.75, 1.05), p = 0.18; I2: 69%]. Intracranial hemorrhage [HR 0.42 (95% CI 0.22, 0.80), p = 0.008; I2: 73%] were lower in the DOAC group.Conclusion: This meta-analysis indicates that DOACs were associated with a lower risk of SSE and intracranial hemorrhage compared with patients receiving warfarin. There was no significant difference between the two groups in terms of major bleeding.

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Comparison of the Direct Oral Anticoagulants and Warfarin in Patients With Atrial Fibrillation and Valvular Heart Disease: Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.712585 ◽

2021 ◽

Vol 8 ◽

Author(s):

Yasmin de Souza Lima Bitar ◽

Andre Rodrigues Duraes ◽

Leonardo Roever ◽

Mansueto Gomes Neto ◽

Liliane Lins-Kusterer ◽

...

Keyword(s):

Atrial Fibrillation ◽

Systematic Review ◽

Heart Disease ◽

Major Bleeding ◽

Valvular Heart Disease ◽

Meta Analysis ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Risk Of Bias ◽

Efficacy And Safety

Background: Direct oral anticoagulants (DOACS) are approved for use in non-valvular atrial fibrillation (AF). This systematic review and meta-analysis aimed to evaluate the efficacy and safety of DOACs vs. warfarin and update the evidence for treatment of AF and valvular heart disease (VHD).Methods: We identified randomized clinical trials (RCTs) and post-hoc analyses comparing the use of DOACS and Warfarin in AF and VHD, including biological and mechanical heart valves (MHV), updating from 2010 to 2020. Through systematic review and meta-analysis, by using the “Rev Man” program 5.3, the primary effectiveness endpoints were stroke and systemic embolism (SE). The primary safety outcome was major bleeding, while the secondary outcome included intracranial hemorrhage. We performed prespecified subgroup analyses. Data were analyzed by risk ratio (RR) and 95% confidence interval (CI) and the I-square (I2) statistic as a quantitative measure of inconsistency. Risk of bias and methodological quality assessment of included trials was evaluated with the modified Cochrane risk-of-bias tool.Results: We screened 326 articles and included 8 RCTs (n = 14.902). DOACs significantly reduced the risk of stroke/SE (RR 0.80, 95% CI: 0.68–0.94; P = 0.008; moderate quality evidence; I2 = 2%) and intracranial hemorrhage (RR 0.40, 95% CI: 0.24–0.66; P = 0.0004; I2 = 49%) with a similar risk of major bleeding (RR 0.83, 95% CI: 0.56–1.24; P = 0.36; I2 = 88%) compared to Warfarin.Conclusions: In this update, DOACs remained with similar efficacy and safety compared to warfarin in thromboprophylaxis for AF and VHD.

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Oral anticoagulants in atrial fibrillation with valvular heart disease and bioprosthetic heart valves

Heart ◽

10.1136/heartjnl-2019-314767 ◽

2019 ◽

Vol 105 (18) ◽

pp. 1432-1436 ◽

Cited By ~ 7

Author(s):

Aaqib H Malik ◽

Srikanth Yandrapalli ◽

Wilbert S Aronow ◽

Julio A Panza ◽

Howard A Cooper

Keyword(s):

Atrial Fibrillation ◽

Heart Disease ◽

Major Bleeding ◽

Valvular Heart Disease ◽

Heart Valves ◽

Meta Analysis ◽

Oral Anticoagulants ◽

Cardiac Events ◽

Increased Risk ◽

Randomised Controlled

ObjectiveCurrent guidelines endorse the use of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation (AF). However, little is known about their safety and efficacy in valvular heart disease (VHD). Similarly, there is a paucity of data regarding NOACs use in patients with a bioprosthetic heart valve (BPHV). We, therefore, performed a network meta-analysis in the subgroups of VHD and meta-analysis in patients with a BPHV.MethodsPubMed, Cochrane and Embase were searched for randomised controlled trials. Summary effects were estimated by the random-effects model. The outcomes of interest were a stroke or systemic embolisation (SSE), myocardial infarction (MI), all-cause mortality, major adverse cardiac events, major bleeding and intracranial haemorrhage (ICH).ResultsIn patients with VHD, rivaroxaban was associated with more ICH and major bleeding than other NOACs, while edoxaban 30 mg was associated with least major bleeding. Data combining all NOACs showed a significant reduction in SSE, MI and ICH (0.70, [0.57 to 0.85; p<0.001]; 0.70 [0.50 to 0.99; p<0.002]; and 0.46 [0.24 to 0.86; p<0.01], respectively). Analysis of 280 patients with AF and a BPHV showed similar outcomes with NOACs and warfarin.ConclusionsNOACs performed better than warfarin for a reduction in SSE, MI and ICH in patients with VHD. Individually NOACs performed similarly to each other except for an increased risk of ICH and major bleeding with rivaroxaban and a reduced risk of major bleeding with edoxaban 30 mg. In patients with a BPHV, results with NOACs seem similar to those with warfarin and this needs to be further explored in larger studies.

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

European Heart Journal ◽

10.1093/eurheartj/ehz745.0021 ◽

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.

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Abstract 12465: Dabigatran in Real World of Atrial Fibrillation: Systematic Review and Meta-analysis of Comparison Studies With Vitamin K Antagonists

Circulation ◽

10.1161/circ.132.suppl_3.12465 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

João Carmo ◽

Francisco M Costa ◽

Jorge Ferreira ◽

Miguel Mendes

Keyword(s):

Myocardial Infarction ◽

Atrial Fibrillation ◽

Systematic Review ◽

Intracranial Hemorrhage ◽

Vitamin K ◽

Major Bleeding ◽

Real World ◽

Observational Studies ◽

Meta Analysis ◽

Vitamin K Antagonists

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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Non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation and valvular heart disease: systematic review and meta-analysis

European Heart Journal - Cardiovascular Pharmacotherapy ◽

10.1093/ehjcvp/pvx028 ◽

2017 ◽

Vol 4 (2) ◽

pp. 111-118 ◽

Cited By ~ 15

Author(s):

Daniel Caldeira ◽

Cláudio David ◽

João Costa ◽

Joaquim J Ferreira ◽

Fausto J Pinto

Keyword(s):

Atrial Fibrillation ◽

Systematic Review ◽

Heart Disease ◽

Vitamin K ◽

Valvular Heart Disease ◽

Meta Analysis ◽

Oral Anticoagulants ◽

Vitamin K Antagonist

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

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.757188 ◽

2021 ◽

Vol 8 ◽

Author(s):

Fuwei Liu ◽

Yunyao Yang ◽

Winglam Cheng ◽

Jianyong Ma ◽

Wengen Zhu

Keyword(s):

Atrial Fibrillation ◽

Systematic Review ◽

Propensity Score ◽

Vitamin K ◽

Major Bleeding ◽

Observational Studies ◽

Meta Analysis ◽

Oral Anticoagulants ◽

Vitamin K Antagonist ◽

Systemic Embolism

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.

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Oral anticoagulants for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis, and cost effectiveness analysis

BMJ ◽

10.1136/bmj.j5058 ◽

2017 ◽

pp. j5058 ◽

Cited By ~ 155

Author(s):

José A López-López ◽

Jonathan A C Sterne ◽

Howard H Z Thom ◽

Julian P T Higgins ◽

Aroon D Hingorani ◽

...

Keyword(s):

Atrial Fibrillation ◽

Systematic Review ◽

Cost Effectiveness ◽

Major Bleeding ◽

Meta Analysis ◽

Oral Anticoagulants ◽

Randomised Trials ◽

Systemic Embolism ◽

Once Daily ◽

Effectiveness Analysis

Abstract Objective To compare the efficacy, safety, and cost effectiveness of direct acting oral anticoagulants (DOACs) for patients with atrial fibrillation. Design Systematic review, network meta-analysis, and cost effectiveness analysis. Data sources Medline, PreMedline, Embase, and The Cochrane Library. Eligibility criteria for selecting studies Published randomised trials evaluating the use of a DOAC, vitamin K antagonist, or antiplatelet drug for prevention of stroke in patients with atrial fibrillation. Results 23 randomised trials involving 94 656 patients were analysed: 13 compared a DOAC with warfarin dosed to achieve a target INR of 2.0-3.0. Apixaban 5 mg twice daily (odds ratio 0.79, 95% confidence interval 0.66 to 0.94), dabigatran 150 mg twice daily (0.65, 0.52 to 0.81), edoxaban 60 mg once daily (0.86, 0.74 to 1.01), and rivaroxaban 20 mg once daily (0.88, 0.74 to 1.03) reduced the risk of stroke or systemic embolism compared with warfarin. The risk of stroke or systemic embolism was higher with edoxaban 60 mg once daily (1.33, 1.02 to 1.75) and rivaroxaban 20 mg once daily (1.35, 1.03 to 1.78) than with dabigatran 150 mg twice daily. The risk of all-cause mortality was lower with all DOACs than with warfarin. Apixaban 5 mg twice daily (0.71, 0.61 to 0.81), dabigatran 110 mg twice daily (0.80, 0.69 to 0.93), edoxaban 30 mg once daily (0.46, 0.40 to 0.54), and edoxaban 60 mg once daily (0.78, 0.69 to 0.90) reduced the risk of major bleeding compared with warfarin. The risk of major bleeding was higher with dabigatran 150 mg twice daily than apixaban 5 mg twice daily (1.33, 1.09 to 1.62), rivaroxaban 20 mg twice daily than apixaban 5 mg twice daily (1.45, 1.19 to 1.78), and rivaroxaban 20 mg twice daily than edoxaban 60 mg once daily (1.31, 1.07 to 1.59). The risk of intracranial bleeding was substantially lower for most DOACs compared with warfarin, whereas the risk of gastrointestinal bleeding was higher with some DOACs than warfarin. Apixaban 5 mg twice daily was ranked the highest for most outcomes, and was cost effective compared with warfarin. Conclusions The network meta-analysis informs the choice of DOACs for prevention of stroke in patients with atrial fibrillation. Several DOACs are of net benefit compared with warfarin. A trial directly comparing DOACs would overcome the need for indirect comparisons to be made through network meta-analysis. Systematic review registration PROSPERO CRD 42013005324.

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