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Archontakis Barakakis P, Kokkinidis DG, Li W, Nagraj S, Peppas S, Kladas M, Schizas D, Korantzopoulos P, Ntaios G. Safety of Direct Oral Anticoagulants for Gastrointestinal Hemorrhage in Patients With Nonvalvular Atrial Fibrillation: A Systematic Review and Meta-analysis of Real-world Studies. J Clin Gastroenterol 2023; 57:1045-1053. [PMID: 36730651 DOI: 10.1097/mcg.0000000000001796] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Accepted: 10/07/2022] [Indexed: 02/04/2023]
Abstract
GOALS AND BACKGROUND Since the introduction of Direct Oral Anticoagulants (DOACs), "real-world" studies have investigated their safety profile on gastrointestinal hemorrhage (GIH) when used by patients with Non-Valvular Atrial Fibrillation. We performed a systematic review and meta-analysis to compile and summarize this data after Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. STUDY Medline and Embase were systematically searched until April 2021. Observational studies that met predefined inclusion criteria were included and hazard ratios (HRs) with 95% CI were extracted. Subgroup analyses based on DOAC doses, history of chronic kidney disease, stroke, prior exposure to VKA (vitamin K antagonist), age, gender, geographic location of population samples, as well as Leave-One-Out and Low/Moderate Risk of Bias sensitivity analyses were performed. A random effects model was used. RESULTS A total of 46 studies were included. Apixaban was associated with a reduced risk of GIH compared with Dabigatran (HR: 0.67, 95% CI, 0.56 to 0.81, I2 : 53.28%), Rivaroxaban (HR: 0.56, 95% CI, 0.44 to 0.70, I2 : 79.17%), and VKA (HR: 0.68, 95% CI, 0.60 to 0.78, I2 : 71.93%). Rivaroxaban was associated with increased GIH risk compared with Dabigatran (HR: 1.19, 95% CI, 1.02 to 1.40, I2 : 72.96%) and VKA (HR: 1.16, 95% CI, 1.05 to 1.27, I2 : 81.95%). Dabigatran was associated with similar GIH risk compared with VKA (HR: 1.11, 95% CI, 0.98 to 1.26, I2 : 87.28%). CONCLUSIONS Our study shows that Apixaban was associated with a reduction in GIH risk compared with Dabigatran, Rivaroxaban and VKA, whereas Rivaroxaban was associated with an increase in GIH risk compared with both Dabigatran and VKA.
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Affiliation(s)
| | - Damianos G Kokkinidis
- Section of Cardiovascular Medicine, Yale University School of Medicine, Yale New Haven Hospital, New Haven, CT
| | - Weijia Li
- Department of Medicine, New York City Health and Hospitals/Jacobi, Albert Einstein College of Medicine
| | - Sanjana Nagraj
- Department of Medicine, New York City Health and Hospitals/Jacobi, Albert Einstein College of Medicine
| | - Spyros Peppas
- Department of Internal Medicine, Naval and VA Hospital of Athens
| | - Michail Kladas
- Department of Medicine, James J. Peters VA Medical Center, North Central Bronx Hospital, Bronx, NY
| | | | | | - George Ntaios
- Department of Internal Medicine, University of Thessaly, Larissa, Greece
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Abrignani MG, Lombardo A, Braschi A, Renda N, Abrignani V, Lombardo RM. Time trends in antithrombotic therapy prescription patterns: Real-world monocentric study in hospitalized patients with atrial fibrillation. World J Cardiol 2022; 14:576-598. [PMID: 36483763 PMCID: PMC9724000 DOI: 10.4330/wjc.v14.i11.576] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2022] [Revised: 07/04/2022] [Accepted: 10/28/2022] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND Since 2010, the European Society of Cardiology has extended prescription criteria for oral antithrombotic therapy (OAT) in atrial fibrillation (AF). Direct oral anticoagulants (DOACs) were upgraded from an IIAa recommendation in 2012 to an IA in 2016. In real-world scenarios, however, OAC prescription is still suboptimal, mainly for DOACs.
AIM To evaluate OAT temporal prescription patterns in a cohort of patients hospitalized with AF in a Cardiology Department.
METHODS A retrospective observational study was conducted on a cohort of hospitalized patients in a secondary setting (Trapani, Italy) from 2010 to 2021 with AF as the main or secondary diagnosis. For 4089 consecutive patients, the variables extracted from the Cardiology department database were: Sex, age, time of hospitalization, antithrombotic therapy (warfarin, acenocoumarol, apixaban, dabigatran, edoxaban, rivaroxaban, aspirin, clopidogrel, other antiplatelet agents, low molecular weight heparin, and fondaparinux), diagnosis at discharge and used resources. Basal features are presented as percentage values for categorized variables and as mean +/- SD for categorized once.
RESULTS From January 1st, 2010 to October 6th, 2021, 25132 patients were hospitalized in our department; 4089 (16.27%, mean age 75.59+/-10.82) were discharged with AF diagnosis; of them, 2245 were males (54.81%, mean age 73.56+/-11.45) and 1851 females (45.19%, mean age 78.06+/-9.47). Average length of stay was 5.76+/-4.88 days; 154 patients died and 88 were moved to other Departments/Structures. AF was the main diagnosis in 899 patients (21.94%). The most frequent main diagnosis in patients with AF was acute myocardial infarction (1973 discharges, 48.19%). The most frequent secondary cardiac diagnosis was chronic coronary syndrome (1864 discharges, 45.51%), and the most frequent secondary associated condition was arterial hypertension (1010 discharges, 24.66%). For the analysis of antithrombotic treatments, the final sample included 3067 patients, after excluding in-hospital deaths, transferred out or self-discharged patients, as well as discharges lacking indications for prescribed treatments. OAC treatment increased significantly (35.63% in 2010-2012 vs 61.18% in 2019-2021, +25.55%, P < 0.0001), in spite of any antiplatelet agent use. This rise was due to increasing use of DOACs, with or without antiplatelet agents, from 3.04% in 2013-2015 to 50.06% in 2019-2021 (+47.02%, P < 0.0001) and was greater for factor Xa inhibitors, especially apixaban. In addition, treatment with a vitamin K antagonist, in spite of any antiplatelet agent use, decreased from 35.63% in 2010-2012 to 11.12% in 2019-2021 (-24.48%, P < 0.0001), as well as any antiplatelet therapy, alone or in double combination, (49.18% in 2010-2012 vs 34.18% in 2019-2021, -15.00%, P < 0.0001); and patients not receiving antithrombotic therapy declined with time (14.58% in 2010-2012 vs 1.97% in 2021, P < 0.0001).
CONCLUSION Real-world patients with AF are elderly and affected by cardiovascular and non-cardiovascular diseases. The percentage of patients on OAT and DOACs increased. These data suggest a slow, gradual guidelines implementation process.
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Affiliation(s)
- Maurizio Giuseppe Abrignani
- Operative Unit of Cardiology, Department of Medicine, S. Antonio Abate Hospital of Trapani, ASP Trapani, Trapani 91100, Trapani, Italy
| | - Alberto Lombardo
- Operative Unit of Cardiology, Department of Medicine, S. Antonio Abate Hospital of Trapani, ASP Trapani, Trapani 91100, Trapani, Italy
| | - Annabella Braschi
- Department of Psychology, Educational Science and Human Movement, University of Palermo, Palermo 90100, Palermo, Italy
| | - Nicolò Renda
- Department of Medicine and Surgery, University of Parma, Parma 43100, Parma, Italy
| | - Vincenzo Abrignani
- Operative Unit of Internal Medicine with Stroke Care, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (ProMISE) "G. D'Alessandro", University of Palermo, Palermo 90100, Palermo, Italy
| | - Renzo M Lombardo
- Department of Cardiology, Operative Unit of Cardiology, Department of Medicine, S. Antonio Abate Hospital of Trapani, Trapani 91100, Trapani, Italy
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Archontakis-Barakakis P, Kokkinidis DG, Nagraj S, Gidwani V, Mavridis T, Ntaios G. Major Hemorrhage Risk Associated with Direct Oral Anticoagulants in Non-Valvular Atrial Fibrillation: A Systematic Review and Meta-Analysis. Rev Cardiovasc Med 2022; 23:334. [PMID: 39077138 PMCID: PMC11267317 DOI: 10.31083/j.rcm2310334] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Revised: 09/15/2022] [Accepted: 09/19/2022] [Indexed: 07/31/2024] Open
Abstract
Background Real-world, observational studies have investigated the safety profile of Direct Oral Anticoagulants (DOACs) on Major Hemorrhage (MH) used for stroke prevention in Non-Valvular Atrial Fibrillation (NVAF). We performed a systematic review and meta-analysis to investigate the comparative safety of DOACs versus other DOACs and versus Vitamin K Antagonists (VKAs) adhering to PRISMA guidelines. We defined MH according to the International Society on Thrombosis and Haemostasis statement or as the composite outcome of intracranial, gastrointestinal, genitourinary, respiratory, cavitary and musculoskeletal bleeding in case of studies using International Statistical Classification of Diseases codes for patient selection. Methods We systematically investigated two databases (Medline, Embase) until April of 2021, gathered observational studies and extracted hazard ratios (HRs) with 95% confidence intervals (CI) on our outcome of interest. Additional subgroup analyses according to DOAC dosing, prior diagnosis of chronic kidney disease, prior diagnosis of stroke, history of previous use of VKA, the users' age, the users' gender and study population geographic region were conducted. All analyses were performed with a random-effects model. Results From this search, 55 studies were included and 76 comparisons were performed. The MH risk associated with Rivaroxaban use was higher than the risk with Dabigatran use (HR: 1.32, 95% CI: 1.21-1.45, I 2 : 12.39%) but similar to VKA use (HR: 0.94, 95% CI: 0.87-1.02, I 2 : 76.57%). The MH risk associated with Dabigatran use was lower than the risk with VKA use (HR: 0.75, 95% CI: 0.64-0.90, I 2 : 87.57%). The MH risk associated with Apixaban use was lower than the risk with Dabigatran use (HR: 0.75, 95% CI: 0.64-0.88, I 2 : 58.66%), with Rivaroxaban use (HR: 0.58, 95% CI: 0.50-0.68, I 2 : 74.16%) and with VKA use (HR: 0.60, 95% CI: 0.55-0.65, I 2 : 58.83%). Our aforementioned subgroup analyses revealed similar results. Conclusions All in all, Apixaban was associated with a reduced MH risk compared to Dabigatran, Rivaroxaban and VKA. Dabigatran was associated with a reduced MH risk compared to both Rivaroxaban and VKA.
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Affiliation(s)
| | - Damianos G. Kokkinidis
- Section of Cardiovascular Medicine, Yale University School of Medicine, Yale New Haven Hospital, New Haven, CT 06510, USA
| | - Sanjana Nagraj
- Department of Medicine, Albert Einstein College of Medicine/Jacobi Medical Center, Bronx, NY 10461, USA
| | - Vipul Gidwani
- Northeast Internal Medicine Associates, LaGrange, IN 46845, USA
| | | | - George Ntaios
- Department of Internal Medicine, University of Thessaly, 38221 Larissa, Greece
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Archontakis-Barakakis P, Li W, Kalaitzoglou D, Tzelves L, Manolopoulos A, Giannopoulos S, Giamouzis G, Giannakoulas G, Batsidis A, Palaiodimos L, Ntaios G, Lip GYH, Kokkinidis DG. Effectiveness and Safety of Intracranial Events associated with the use of Direct Oral Anticoagulants for Atrial Fibrillation: A Systematic Review and Meta-analysis of 92 Studies. Br J Clin Pharmacol 2022; 88:4663-4675. [PMID: 35853612 DOI: 10.1111/bcp.15464] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Revised: 04/17/2022] [Accepted: 07/14/2022] [Indexed: 11/28/2022] Open
Abstract
AIM Observational studies have investigated the effectiveness and safety of Direct Oral Anticoagulants (DOACs) and Vitamin K antagonists (VKA) used in Non-Valvular Atrial Fibrillation. We performed a systematic review and meta-analysis assessing the risk of ischemic stroke, Thromboembolism (TE) and Intracranial Hemorrhage (ICH) associated with the use of DOACs and VKA. METHODS Medline and Embase were systematically searched until April 2021. Observational studies were gathered and hazard ratios (HRs) with 95% confidence intervals (CI) were extracted. Subgroup analyses based on DOAC doses, history of chronic kidney disease, stroke, exposure to VKA, age, and gender were performed. A random-effects model was used. RESULTS We included 92 studies and performed 107 comparisons. Apixaban was associated with lower risk of stroke [HR: 0.82, 95% CI: 0.68-0.99] compared to Dabigatran. Rivaroxaban was associated with lower risk of stroke [HR: 0.90, 95% CI: 0.83-0.98] compared to VKA. Dabigatran [HR: 0.85, 95% CI: 0.80-0.91], Rivaroxaban [HR: 0.83, 95% CI: 0.77-0.89] and Apixaban [HR: 0.75, 95% CI: 0.65-0.86] were associated with lower risk for TE/stroke compared to VKA. Apixaban [HR: 1.32, 95% CI: 1.03-1.68] and Rivaroxaban [HR: 1.58, 95% CI: 1.31-1.89] were associated with higher risk of ICH compared to Dabigatran. Dabigatran [HR: 0.48, 95% CI: 0.44-0.52], Apixaban [HR: 0.60, 95% CI: 0.49-0.73] and Rivaroxaban [HR: 0.73, 95% CI: 0.65-0.81] were associated with lower risk of ICH compared to VKA. CONCLUSIONS Our study demonstrated significant differences in the risk of ischemic stroke, TE/stroke, and ICH associated with individual DOACs compared to both other DOACs and VKA.
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Affiliation(s)
| | - Weijia Li
- Department of Medicine, Albert Einstein College of Medicine/Jacobi Medical Center, Bronx, NY, USA
| | - Dimitrios Kalaitzoglou
- Department of Neurosurgery, King's College Hospital NHS Foundation Trust, Denmark Hill, London, UK
| | - Lazaros Tzelves
- 2nd Department of Urology, National and Kapodistrian University of Athens, Sismanogleion Hospital, Athens, Greece
| | | | - Stefanos Giannopoulos
- Division of Vascular and Endovascular Surgery, Department of Surgery, Stony Brook University Hospital, Stony Brook, NY, USA
| | | | - George Giannakoulas
- Division of Cardiology, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | | | - Leonidas Palaiodimos
- Department of Medicine, Albert Einstein College of Medicine/Jacobi Medical Center, Bronx, NY, USA
| | - George Ntaios
- Department of Internal Medicine, University of Thessaly, Larissa, Greece
| | - Gregory Y H Lip
- Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, UK
| | - Damianos G Kokkinidis
- Section of Cardiovascular Medicine, Yale University School of Medicine, Yale New Haven Hospital, New Haven, CT, USA
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