Outcomes in anticoagulated patients with atrial fibrillation and with mitral or aortic valve disease

ObjectiveTo assess stroke/systemic embolism, major bleeding and other outcomes, and treatment effect of apixaban versus warfarin, in patients with atrial fibrillation (AF) and different types of valvular heart disease (VHD), using data from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial.MethodsThere were 14 793 patients with known VHD status, categorised as having moderate or severe mitral regurgitation (MR) (n=3382), aortic regurgitation (AR) (n=842) or aortic stenosis (AS) (n=324); patients with moderate or severe mitral stenosis were excluded from the trial. Baseline characteristics, efficacy and safety outcomes were compared between each type and no significant VHD. Treatment effect was assessed using an adjusted model.ResultsPatients with MR or AR had similar rates of stroke/systemic embolism and bleeding compared with patients without MR or AR, respectively. Patients with AS had significantly higher event rates (presented as rate per 100 patient-years of follow-up) of stroke/systemic embolism (3.47 vs 1.36; adjusted HR (adjHR) 2.21, 95% CI 1.35 to 3.63), death (8.30 vs 3.53; adjHR 1.92, 95% CI 1.41 to 2.61), major bleeding (5.31 vs 2.53; adjHR 1.80, 95% CI 1.19 to 2.75) and intracranial bleeding (1.29 vs 0.51; adjHR 2.54, 95% CI 1.08 to 5.96) than patients without AS. The superiority of apixaban over warfarin on stroke/systemic embolism was similar in patients with versus without MR (HR 0.69, 95% CI 0.46 to 1.04 vs HR 0.79, 95% CI 0.63 to 1.00; interaction P value 0.52), with versus without AR (HR 0.57, 95% CI 0.27 to 1.20 vs HR 0.78, 95% CI 0.63 to 0.96; interaction P value 0.52), and with versus without AS (HR 0.44, 95% CI 0.17 to 1.13 vs HR 0.79, 95% CI 0.64 to 0.97; interaction P value 0.19). For each of the primary and secondary efficacy and safety outcomes, there was no evidence of a different effect of apixaban over warfarin in patients with any VHD subcategory.ConclusionsIn anticoagulated patients with AF, AS is associated with a higher risk of stroke/systemic embolism, bleeding and death. The efficacy and safety benefits of apixaban compared with warfarin were consistent, regardless of presence of MR, AR or AS.Clinical trial registrationARISTOTLE clinical trial number NCT00412984.

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6072Risk of stroke in hypertensive patients with atrial fibrillation treated with oral anticoagulants

European Heart Journal ◽

10.1093/eurheartj/ehz746.0121 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

R E Harskamp ◽

W A M Lucassen ◽

R D Lopes ◽

H C Van Weert

Keyword(s):

Atrial Fibrillation ◽

Blood Pressure ◽

Vitamin K ◽

Major Bleeding ◽

Oral Anticoagulants ◽

Haemorrhagic Stroke ◽

Uncontrolled Hypertension ◽

P Value ◽

Systemic Embolism ◽

History Of

Abstract Background Hypertension is common in patients with atrial fibrillation (AF) and carries an additional risk for complications, most notably stroke and bleeding. We assessed the history of hypertension, level of blood pressure control, and an interaction with the choice of oral anticoagulants on clinical outcomes. Purpose To gain insights into the risks of hypertension in the setting of AF and explore possible interactions with the safety and efficacy of non-vitamin K oral anticoagulants (NOACs) versus vitamin K antagonists (VKAs). Methods We performed a systematic review and meta-analysis of studies that randomised patients to NOACs or VKAs and reported outcomes stratified by presence of hypertension. Collected outcomes included: ischaemic stroke or systemic embolism (SE), death from any cause, hemorrhagic stroke, major bleeding, and intracranial hemorrhage. Log adjusted hazard ratios (HR) and corresponding standard error were calculated, and HRs were compared using Mantel-Haenszel random effects. Quality of the evidence was assessed with Cochrane risk of bias tool. Results Five high-quality studies were eligible, including 71,602 participants who received NOACs (apixaban, dabigatran, edoxaban, rivaroxaban) or VKAs, with median follow-up of 1.8–2.8 years. 89.2% of participants had a history of hypertension. Compared with patients without hypertension, those with controlled and uncontrolled hypertension had higher risk for stroke/SE (HR: 1.21 [1.04–1.41] and HR: 1.50 [1.12–2.01], respectively) and haemorrhagic stroke (HR: 1.78 [1.06, 3.00] and HR: 1.66 [0.99–4.01], respectively). On a continuous scale, the risk of stroke increased 7% per 10mmHg increase in systolic blood pressure. As shown in the Table, no interactions were found between hypertension status and the efficacy or safety of NOACs versus VKAs. Table 1. Interaction of presence of hypertension on the comparative efficacy and safety of NOAC versus VKA Hypertension (n=63,869) No hypertension (n=7,733) P-value (int) Adjusted HR, 95% CI Adjusted HR, 95% CI Stroke or systemic embolism 080, 0.72–0.89 0.79, 0.53–1.19 0.98 Haemorrhagic stroke 0.55, 0.41–0.74 0.24, 0.04–1.37 0.36 Death from any cause 0.91, 0.84–0.98 0.89, 0.76–1.04 0.82 Major bleeding 0.90, 0.76–1.07 0.84, 0.69–1.01 0.57 Intracranial haemorrhage 0.41, 0.24-.068 0.48, 0.14–1.69 0.81 Major or clinically relevant non-major bleed 0.90, 0.68–1.18 0.91, 0.55–1.53 0.96 Conclusions Adequate blood pressure management is vital to optimally reduce the risk of stroke in patients with atrial fibrillation. The benefits of NOACs over VKAs, also apply to patients with elevated blood pressure.

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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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Long-Term Treatment with Apixaban in Patients with Atrial Fibrillation: Outcomes during the Open-Label Extension following AVERROES

Thrombosis and Haemostasis ◽

10.1055/s-0040-1717115 ◽

2020 ◽

Author(s):

Alexander P. Benz ◽

John W. Eikelboom ◽

Salim Yusuf ◽

Stefan H. Hohnloser ◽

Anja Kahl ◽

...

Keyword(s):

Atrial Fibrillation ◽

Major Bleeding ◽

Hemorrhagic Stroke ◽

Efficacy And Safety ◽

Systemic Embolism ◽

Open Label ◽

Long Term Treatment ◽

Open Label Extension ◽

Event Rates

Abstract Background AVERROES, a randomized controlled trial in high-risk patients with atrial fibrillation, unsuitable for vitamin K antagonist therapy, demonstrated efficacy and safety of apixaban compared with aspirin. At the conclusion of the double-blind phase, an open-label extension was initiated to allow study participants to receive apixaban until it became locally available. This study reports outcomes of patients on apixaban during the open-label extension. Methods Rates of stroke or systemic embolism, hemorrhagic stroke, major bleeding, and other outcomes during the open-label extension are reported. Results Of the 5,599 participants enrolled in AVERROES, 3,275 (58.5%) received apixaban during the open-label extension. Median (interquartile range) follow-up in the open-label extension was 3.0 (2.5–3.5) years. The rate of stroke or systemic embolism during the open-label extension was 1.0% per year, and the annual rates of hemorrhagic stroke and major bleeding were 0.3 and 1.2%, respectively. After adjustment for imbalances in patient variables, event rates in patients on apixaban during the open-label extension were similar to those of patients receiving apixaban during AVERROES. Additional analyses in all patients who received apixaban, at any time from the start of AVERROES to the end of the open-label extension, were performed. This cohort (n = 4,414) showed annual event rates of 1.1% for stroke or systemic embolism, 0.3% for hemorrhagic stroke, and 1.2% for major bleeding. Conclusion During the open-label extension, annual rates of stroke or systemic embolism, hemorrhagic stroke, and major bleeding remained as low as those observed during apixaban treatment in AVERROES. These data support the long-term efficacy and safety of apixaban in patients with atrial fibrillation.

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Thromboembolic risks associated with paroxysmal and persistent atrial fibrillation in Asian patients: a report from the Chinese atrial fibrillation registry

BMC Cardiovascular Disorders ◽

10.1186/s12872-019-1260-7 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 5

Author(s):

Ying Wang ◽

Chang-Sheng Ma ◽

Xin Du ◽

Liu He ◽

Jie Li ◽

...

Keyword(s):

Atrial Fibrillation ◽

Clinical Trial ◽

Cardiac Death ◽

Persistent Atrial Fibrillation ◽

Clinical Trial Registry ◽

Clinical Trial Registration ◽

Asian Patients ◽

Significant Difference ◽

Chinese Cohort ◽

Anticoagulated Patients

Abstract Background Several studies have reported on atrial fibrillation (AF) outcomes, including thromboembolism in patients with paroxysmal and non-paroxysmal AF; however the findings still remain controversial on whether risks differ between these clinical subtypes and limited data are available in Asian cohorts. Methods We compared the risk of thromboembolism between paroxysmal and persistent AF patients, in a large contemporary Chinese cohort study. A total of 8529 non-valvular atrial fibrillation (NVAF) patients from the Chinese Atrial Fibrillation Registry (CAFR) study were enrolled. The study subjects were divided into two groups: paroxysmal AF (PaAF, defined as AF lasting within 7 days, n = 4642) and persistent AF (PeAF, lasting over 7 days, n = 3887) groups. Results In non-anticoagulated patients, PeAF group demonstrated a higher risk of stroke, all-cause death, cardiac/ non-cardiac death and composition of stroke/ transient ischemic attack (TIA)/peripheral thromboembolism (PT)/all-cause death, compared to the PaAF group. No significant difference was found in anticoagulated subjects. On multivariate analysis in non-anticoagulated patients, age ≥ 75 years (P = 0.046) and prior stroke/TIA/PT (P = 0.018) but not AF type (P = 0.63) were significantly associated with the risk of stroke/TIA/PT events. Conclusions Stroke, all-cause death and cardiac/non-cardiac death in Chinese NVAF population was increased in non-anticoagulated PeAF patients compared with PaAF group, but same between anticoagulated PeAF and PaAF patients. After adjustment, AF type was not an independent predictor of thromboembolism in NVAF patients. Clinical trial registration Chinese Clinical Trial Registry ChiCTR-OCH-13003729. Registered 22 October 2013.

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Efficacy and Safety of Non-Vitamin K Anticoagulants for Atrial Fibrillation in Relation to Different Renal Function Levels: A Network Meta-Analysis

Cardiovascular Therapeutics ◽

10.1155/2020/2683740 ◽

2020 ◽

Vol 2020 ◽

pp. 1-26

Author(s):

Hao Jin ◽

Kongbo Zhu ◽

Lina Wang ◽

Yifan Li ◽

Jingjun Meng ◽

...

Keyword(s):

Atrial Fibrillation ◽

Renal Function ◽

Renal Impairment ◽

Major Bleeding ◽

Normal Renal Function ◽

Meta Analysis ◽

Effective Drug ◽

Efficacy And Safety ◽

Systemic Embolism ◽

Mild Renal Impairment

Background. We performed a network meta-analysis (NMA) comparing the efficacy (stroke or systemic embolism) and safety (major bleeding) among different non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) and renal impairment, with the aim of recommending the proper drug and the dose based on renal function. Methods. We searched PubMed, EMBASE, Web of Science, and Cochrane Library with the items “dabigatran, edoxaban, apixaban, rivaroxaban, warfarin, and atrial fibrillation” through August 2019. NMA was analyzed with R (version 3.5.1, R Foundation for Statistical Computing) with the packages gemtc recalling JAGS (version 4.3.0) for the efficacy and safety of each drug with regard to different levels of renal function. NetMetaXL (version 1.6.1) and winBUGS (version 1.4.3) were used to obtain the cumulative ranking curve (SUCRA) of each drug. Result. In patients with normal renal function, dabigatran150 was ranked as the most effective drug (SUCRA 0.90), followed by dabigatran110 (SUCRA 0.68), apixaban (SUCRA 0.66), and rivaroxaban (SUCRA 0.59). With regard to the safety for preventing major bleeding, there was high probability that edoxaban30 (SUCRA 0.99) ranked first, compared to dabigatran110 (SUCRA 0.78) and edoxaban60 (SUCRA 0.66). For patients with mild renal impairment, with respect to the most effective drug for preventing stroke or systemic embolism, edoxaban60 ranked first (SUCRA 0.98), in comparison with dabigatran150 (SUCRA 0.74) and apixaban (SUCRA 0.64). Possibility of ranking first for the safest drug was edoxaban30 (SUCRA 0.99), followed by dabigatran110 (SUCRA 0.70) and apixaban (SUCRA 0.69). In patients with moderate renal function, dabigatran150 (SUCRA 0.95) ranked as the most effective drug in comparison with apixaban (SUCRA 0.66). Dabigatran110 (SUCRA 0.53), rivaroxaban (SUCRA 0.51), and edoxaban60 (SUCRA 0.50) had the similar probability of ranking third. When referred to the safest drug, probability of ranking first for preventing major bleeding was edoxaban30 (SUCRA 0.98), followed by apixaban (SUCRA 0.85) and edoxaban60 (SUCRA 0.64). Conclusion. In patients with AF and renal impairment and for patients with normal renal function, dabigatran 110 mg (bid) might have a better effect on the clinical results. And it does not coincide with patients taking dabigatran 110 mg with dose reduction for other factors including aged ≥75 years, renal impairment (CrCL 30–50 mL/min), gastritis, esophagitis, or gastroesophageal reflux, receiving concomitant verapamil, and so on. For patients with mild renal impairment, apixaban 5 mg (bid) would be a better choice for preventing stroke or systemic embolism and major bleeding, while apixaban 5 mg (bid) and edoxaban 60 mg (qd) were recommended for patients with moderate renal impairment. However, considering the fact of no RCTs for the head-to-head comparison, caution should be exercised over selecting each of NOACs for patients.

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The association between patterns of atrial fibrillation, anticoagulation, and cardiovascular events

EP Europace ◽

10.1093/europace/euz292 ◽

2019 ◽

Vol 22 (2) ◽

pp. 195-204 ◽

Cited By ~ 4

Author(s):

Dan Atar ◽

Eivind Berge ◽

Jean-Yves Le Heuzey ◽

Saverio Virdone ◽

A John Camm ◽

...

Keyword(s):

Atrial Fibrillation ◽

Cardiovascular Events ◽

Cox Regression ◽

Risk Calculator ◽

Systemic Embolism ◽

Unique Identifier ◽

Clinical Trial Registration ◽

Risk Of Death ◽

Anticoagulated Patients

Abstract Aims Guidelines do not recommend to take pattern of atrial fibrillation (AF) into account for the indication of anticoagulation (AC). We assessed AF pattern and the risk of cardiovascular events during 2-years of follow-up. Methods and results We categorized AF as paroxysmal, persistent, or permanent in 29 181 patients enrolled (2010–15) in the Global Anticoagulant Registry In the FIELD of AF (GARFIELD-AF). We used multivariable Cox regression to assess the risks of stroke/systemic embolism (SE) and death across patterns of AF, and whether this changed with AC on outcomes. Atrial fibrillation pattern was paroxysmal in 14 344 (49.2%), persistent in 8064 (27.6%), and permanent 6773 (23.2%) patients. Median CHA2DS2-VASc, GARFIELD-AF, and HAS-BLED scores assessing the risk of stroke/SE and/or bleeding were similar across AF patterns, but the risk of death, as assessed by the GARFIELD-AF risk calculator, was higher in non-paroxysmal than in paroxysmal AF patterns. During 2-year follow-up, after adjustment, non-paroxysmal AF patterns were associated with significantly higher rates of all-cause death, stroke/SE, and new/worsening congestive heart failure (CHF) than paroxysmal AF in non-anticoagulated patients only. In anticoagulated patients, a significantly higher risk of death but not of stroke/SE and new/worsening CHF persisted in non-paroxysmal compared with paroxysmal AF patterns. Conclusion In non-anticoagulated patients, non-paroxysmal AF patterns were associated with higher risks of stroke/SE, new/worsening HF and death than paroxysmal AF. In anticoagulated patients, the risk of stroke/SE and new/worsening HF was similar across all AF patterns. Thus AF pattern is no longer prognostic for stroke/SE when patients are treated with anticoagulants. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362.

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Meta-analysis comparing the efficacy and safety of direct acting oral anticoagulants to warfarin in patients with atrial fibrillation with and without diabetes

European Heart Journal ◽

10.1093/ehjci/ehaa946.3378 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

S Shetty ◽

H Malik

Keyword(s):

Atrial Fibrillation ◽

Major Bleeding ◽

Meta Analysis ◽

Oral Anticoagulants ◽

P Value ◽

Efficacy And Safety ◽

Systemic Embolization ◽

Direct Acting ◽

Direct Acting Oral Anticoagulants

Abstract Background Direct-acting oral anticoagulants (DOACs) are now the preferred choice over warfarin in patients with atrial fibrillation (AF). The comparative efficacy and safety of DOACs over warfarin in patients with and without diabetes mellitus (DM) has not been fully evaluated. Purpose To evaluate the efficacy and safety of DOACs compared to warfarin in patients with non-valvular atrial fibrillation with and without DM. Methods A comprehensive review of the literature was performed to identify RCTs with data on DOACs compared to warfarin in the subgroups of DM and nonN-DM. Our outcome of interest were stroke/systemic embolization (SSE) and major bleeding. A random-effects meta-analysis was performed. We further performed a network meta-analysis to assess the most effective of all the therapies for the above mentioned subgroups. Results Our search identified 4 RCTs with 71,683 randomized patients, of which 22,087 were DM and 49,596 were non-DM. The mean duration of follow up was 2.3 years. Our results showed that the DOACS were associated with lower odds for SSE in diabetics (OR 0.80; 95% CI 0.67–0.95; p-value=0.01) and non-diabetics (OR 0.81; 95% CI 0.71–0.92; p-value<0.01). For major bleeding, DOACs were non-inferior to warfarin in DM (OR 0.94; 95% CI 0.80–1.09; p-value=0.42) and non-DM (OR 0.82; 95% CI 0.62–1.07; p-value=0.15). (Fig 1) Network meta-analysis showed that dabigatran was the most effective for the outcome of SSE irrespective of DM status. However, edoxaban and apixaban were the safest of the DOACs for the outcome of major bleeding (Table 1) Conclusion In this meta-analysis of RCT, we found that DOACs are more effective and similarly safe compared to warfarin irrespective of the diabetic status of the patient. Funding Acknowledgement Type of funding source: None

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Apixaban-Calibrated Anti-FXa Activity in Relation to Outcome Events and Clinical Characteristics in Patients with Atrial Fibrillation: Results from the AVERROES Trial

TH Open ◽

10.1055/s-0037-1613679 ◽

2017 ◽

Vol 01 (02) ◽

pp. e139-e145 ◽

Cited By ~ 7

Author(s):

Vinai Bhagirath ◽

John Eikelboom ◽

Jack Hirsh ◽

Michiel Coppens ◽

Jeffrey Ginsberg ◽

...

Keyword(s):

Atrial Fibrillation ◽

Major Bleeding ◽

Clinical Characteristics ◽

Factor Xa ◽

Entire Group ◽

Minor Bleeding ◽

Systemic Embolism ◽

Nonvalvular Atrial Fibrillation ◽

Clinical Trial Registration

Background In patients with nonvalvular atrial fibrillation (AF), apixaban is given in doses of 5 or 2.5 mg twice daily, according to clinical characteristics. The usual on-treatment range of apixaban drug levels, as determined by apixaban-calibrated anti-factor Xa (anti-Xa) activity, has previously been measured in small cohorts; however, the association between anti-Xa activity and clinical outcomes and the predictors of variability in anti-Xa activity have not been well studied in the AF population. Methods and Results Anti-Xa activity was measured before taking the morning dose, 3 months after enrollment in the AVERROES study using a calibrated anti-Xa assay (Rotachrom). Patients with two of the following criteria—age >80; weight <60 kg; or creatinine >133 μg/L—received 2.5 mg twice daily (n = 145), while all others received 5 mg twice daily (n = 2,247). A total of 2,392 patients were included, with median follow-up of 1.1 years. Median apixaban anti-Xa activity was 122 ng/mL (interquartile range [IQR]: 63–198 ng/mL) for the entire group; 99 ng/mL (IQR: 60–146 ng/mL) for the 2.5-mg group; and 125 ng/mL (IQR: 64–202 ng/mL) for the 5-mg group (p = 0.003). A relationship was evident between bleeding and anti-Xa activity (p = 0.01), which was driven by minor bleeding. No relationship was evident between major bleeding or stroke/systemic embolism and anti-Xa activity. In those receiving the 5-mg dose, estimated glomerular filtration rate, sex, and age had the strongest association with anti-Xa activity. Conclusion There is considerable variability in anti-Xa activity among AF patients receiving apixaban. Rates of major bleeding and stroke/systemic embolism were low irrespective of anti-Xa activity. Clinical Trial Registration ClinicalTrials.gov NCT00496769; https://clinicaltrials.gov/ct2/show/NCT00496769.

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

European Heart Journal ◽

10.1093/eurheartj/ehab724.3424 ◽

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 >40 or weight >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 >40 or weight >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<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<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

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