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1.
Double or triple antithrombotic therapy after coronary stenting and atrial fibrillation: A systematic review and meta-analysis of randomized clinical trials.
Andò, G, Costa, F
International journal of cardiology. 2020;:95-102
Abstract
AIMS: Double or triple antithrombotic therapy (DAT/TAT) including or excluding aspirin in association with oral anticoagulant and P2Y12 inhibitor are currently two available options in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI). We evaluated efficacy and safety outcomes for DAT vs. TAT. METHODS AND RESULTS Four non-vitamin K oral anticoagulants (NOAC)-based randomized controlled trials comparing DAT vs. TAT with a total of 10,938 patients were pooled. Bleeding events occurred more frequently than ischemic events. DAT as compared to TAT was associated to an increased risk of stent thrombosis (RR 1.54, 95% CI 1.10-2.14; p = 0.03), myocardial infarction (RR 1.23, 95% CI 1.04-1.46; p = 0.03) and cardiovascular mortality (RR 1.09, 95% CI 1.01-1.19; p = 0.04) and to a reduced risk of ISTH major or clinically relevant non-major bleeding (RR 0.59, 95% CI 0.62-0.93; p = 0.03). A consistent effect was observed in all safety endpoints. Intracranial haemorrhage was numerically reduced by DAT. No difference for all-cause death was observed. CONCLUSION Antithrombotic treatment in patients with AF undergoing PCI represents a trade-off between ischemia and bleeding. A careful patient selection based on baseline ischemic and bleeding risk may optimize the net clinical balance in this population.
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2.
Meta-analysis Comparing Direct Oral Anticoagulants Versus Vitamin K Antagonists After Transcatheter Aortic Valve Implantation.
Ueyama, H, Kuno, T, Ando, T, Briasoulis, A, Fox, J, Hayashida, K, Takagi, H
The American journal of cardiology. 2020;(7):1102-1107
Abstract
Atrial fibrillation (AF) is a common co-morbidity in patients undergoing transcatheter aortic valve implantation (TAVI), but whether direct oral anticoagulants (DOACs) confer similar safety and efficacy compared with vitamin K antagonist (VKA) remains unclear in this population. The aim of our study was to investigate the safety and efficacy of DOACs compared with VKA in patients undergoing TAVI with concomitant indication of oral anticoagulation. PUBMED and EMBASE were searched through October 2019 for studies comparing DOACs versus VKA in patients undergoing TAVI with indication of oral anticoagulation. The main efficacy outcomes were all-cause mortality and stroke whereas the main safety outcome was major and/or life-threatening bleeding. Our search identified 5 eligible studies including 2,569 patients. Majority of patients had atrial fibrillation as indication of anticoagulation. There were no significant differences in all-cause mortality, major and/or life-threatening bleeding, and stroke in patients treated with DOACs versus VKA (odds ratio [OR] 1.07, 95% confidence interval [CI] [0.73 to 1.57], p = 0.72, OR = 0.85, 95% CI [0.64 to 1.12], p = 0.24, OR 1.52, 95% CI [0.93 to 2.48], p = 0.09, respectively). In conclusion, in patients undergoing TAVI with concomitant indication for oral anticoagulation, all-cause mortality, major and/or life-threatening bleeding, and stroke were similar between DOACs and VKA. Further large scale randomized controlled trials are needed to search the optimal oral anticoagulation regimen in this population.
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3.
Meta-analysis of Antithrombotic Therapy in Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention.
Kuno, T, Ueyama, H, Takagi, H, Ando, T, Numasawa, Y, Briasoulis, A, Fox, J, Bangalore, S
The American journal of cardiology. 2020;(4):521-527
Abstract
For patients with atrial fibrillation (AF) who undergo percutaneous coronary intervention (PCI), antithrombotic therapy including oral anticoagulants and antiplatelets are indicated. The optimal combination is not known. We investigated the efficacy and safety of different antithrombotic strategies in patients with AF undergoing PCI. PUBMED and EMBASE were searched through September 2019 for randomized trials investigating the efficacy and safety of different antithrombotic strategies in patients with AF who underwent PCI and/or acute coronary syndrome. Nine antithrombotic strategies were compared including combinations of vitamin K antagonist (VKA) with dual antiplatelet therapy (DAPT) or P2Y12 inhibitor, combinations of direct oral anticoagulants (DOAC) (apixaban, dabigatran, rivaroxaban, and edoxaban) with DAPT or P2Y12 inhibitor (clopidogrel, prasugrel, and ticagrelor). The primary safety outcome was trial defined primary bleeding outcome. The primary efficacy outcome was trial defined major adverse cardiovascular events. Our search identified 5 eligible trials that enrolled a total of 11,532 patients and compared 9 treatment strategies. VKA + DAPT significantly increased bleeding when compared with most combinations (for example, vs VKA + P2Y12 inhibitor: odds ratio 2.11; 95% confidence interval [1.76 to 2.52], p <0.001). Of all the combinations, apixaban + P2Y12 inhibitor showed the lowest bleeding risk (for example, vs VKA + P2Y12 inhibitor: odds ratio 0.63; 95% confidence interval [0.51 to 0.78], p <0.001) and was ranked the best treatment. There were no significant differences in ischemic outcome of major adverse cardiovascular events between various antithrombotic regimens. In conclusion, in patients with AF undergoing PCI, apixaban + P2Y12 inhibitors were associated with lowest bleeding compared with other regimens including other DOACs + P2Y12 inhibitors with no increase in ischemic outcomes.
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4.
Meta-Analysis of Antithrombotic Strategies in Patients With Heart Failure With Reduced Ejection Fraction and Sinus Rhythm.
Ueyama, H, Takagi, H, Briasoulis, A, Harrington, M, Steinberg, D, Kuno, T
The American journal of cardiology. 2020;:92-98
Abstract
Heart failure with reduced ejection fraction (HFrEF) is associated with an increased risk of thrombotic events. We compared the safety and efficacy of different antithrombotic strategies for HFrEF and sinus rhythm. PubMed and Embase were searched through January 2020 for studies comparing oral anticoagulants versus antiplatelet agents or placebo in HFrEF and sinus rhythm to include in this network meta-analysis. We identified 5 randomized controlled trials with a total of 9,390 patients randomized to low dose rivaroxaban, vitamin K antagonist (VKA), antiplatelets, or placebo. Low dose rivaroxaban and VKA did not show a significant decrease in stroke compared with placebo but were associated with an increased risk of major bleeding (risk ratio [RR] 6.86, 95% confidence interval [CI] 1.16 to 40.7; RR 8.62, 95% CI 1.52 to 48.9, respectively). When compared with antiplatelets, low dose rivaroxaban and VKA were associated with a significantly decreased risk of stroke (RR 0.67, 95% CI 0.47 to 0.96; RR 0.50, 95% CI 0.33 to 0.76, respectively), but with a significantly increased risk of major bleeding (RR 1.65, 95% CI 1.16 to 2.33; RR 2.07, 95% CI 1.51 to 2.84, respectively). There was no significant difference in these outcomes between low dose rivaroxaban versus VKA and antiplatelets versus placebo. There were no significant differences in all-cause mortality, myocardial infarction, or rehospitalization for heart failure among each treatment. In conclusion, in patient with HFrEF and sinus rhythm, use of oral anticoagulation with or without antiplatelet agents increases the risk of bleeding without substantial effects on the risk of ischemic stroke.
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5.
Clinical Outcomes of Antithrombotic Strategies for Patients with Atrial Fibrillation After Percutaneous Coronary Intervention.
Gao, X, Ge, Z, Kong, X, Wang, Z, Zuo, G, Wang, F, Chen, S, Zhang, J
International heart journal. 2019;(3):546-553
Abstract
Antithrombotic strategies for patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) remain challenging. This study aims to explore the best antithrombotic strategy for AF patients after PCI based on a network meta-analysis. This study was registered in PROSPERO (CRD42018093928). The PubMed, Cochrane, and EMBASE databases were searched to identify clinical trials concerning antithrombotic therapy for AF patients with PCI from inception to April 2018. Pairwise and network meta-analysis were conducted to compare clinical outcomes of different antithrombotic therapy. The primary endpoint was major bleeding. Fifteen studies including 16,382 patients were identified with follow-up ranging from 3 to 12 months. Non-vitamin K oral anticoagulants (NOAC) plus P2Y12 inhibitor ranked first with a reduced risk of major bleeding compared with vitamin K antagonist (VKA) plus dual antiplatelet therapy (OR: 0.57, 95% CI: 0.43-0.75) but with no significant difference compared with VKA plus single platelet therapy (OR: 0.85, 95% CI: 0.62-1.16). Similar thrombotic events were evident among these groups. Subgroup analysis showed that VKA plus aspirin exhibited a similar risk of major bleeding compared with VKA plus clopidogrel (OR: 0.94, 95% CI: 0.73-1.23) but was associated with increased risks of ischaemic stroke (OR: 2.10, 95% CI: 1.33-3.32) and all-cause death (OR: 1.77, 95% CI: 1.15-2.74) versus VKA plus clopidogrel. In AF patients undergoing PCI, NOAC plus P2Y12 inhibitor and VKA plus clopidogrel, but not VKA plus aspirin, were associated with reduced risk of major bleeding compared with the recommended VKA-based triple therapy, while thrombotic events were similar among these treatments.
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6.
Assessment of Condition and Medication Knowledge Gaps Among Atrial Fibrillation Patients: A Systematic Review and Meta-analysis.
Salmasi, S, De Vera, MA, Barry, A, Bansback, N, Harrison, M, Lynd, LD, Loewen, PS
The Annals of pharmacotherapy. 2019;(8):773-785
Abstract
Background: Patient education facilitates construction of a correct illness representation, improves beliefs about medications, and improves knowledge, factors that have been associated with better adherence. Objective: Our objective was to characterize the published literature about atrial fibrillation (AF) patients' disease and medication knowledge to identify knowledge gaps and misconceptions to inform AF patient education strategies. Methods: Following PRISMA guidelines, we searched PubMed, EMBASE, CINAHL, and PsychINFO from inception to May 2018 for studies that assessed AF patients' knowledge about their condition and medications. For quantitative studies, we extracted the proportion of participants who provided correct answers to the questions asked about their condition, medications, or risk of stroke. We classified data for related questions into knowledge domains. A random-effects meta-analysis was conducted for each knowledge domain. A domain was considered a knowledge gap if the pooled mean proportion of participants who demonstrated knowledge of it was ≤50%, regardless of CI. Qualitative data were summarized narratively. Results: A total of 21 studies were included. AF- and stroke-related knowledge gaps and misconceptions included the following: AF can be asymptomatic, AF can predispose to heart failure, women are at a higher risk of stroke, the definition of ischemic stroke, and patients' awareness of their diagnosis. Medication-related knowledge gaps were antithrombotic-drug interactions, antithrombotic-food interactions, vitamin K content of foods, the term INR (international normalized ratio) and its interpretation, and the required actions in case of a missed dose. Conclusion and Relevance: This systematic review identified several AF patient knowledge gaps about their condition and its treatment that can inform the development of AF patient education programs.
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7.
Triple versus double antithrombotic therapy in patients with atrial fibrillation and stent implantation: a meta‑analysis of randomized trials.
Grajek, S, Olasińska-Wiśniewska, A, Michalak, M, Ritter, SS
Kardiologia polska. 2019;(9):837-845
Abstract
BACKGROUND Appropriate double (DT) and triple (TT) antithrombotic therapy in patients with atrial fibrillation and stent implantation is unclear. AIM: The aim of the study was to perform a meta‑analysis of studies comparing DT and TT in patients with atrial fibrillation and stent implantation. METHODS Of the 450 reports, 5 randomized trials were included in the meta‑analysis: WOEST, ISAR‑REACT, PIONEER AF‑PCI, RE‑DUAL PCI, and AUGUSTUS, with a total of 9931 patients. RESULTS Treatment efficacy, as assessed by the incidence of major adverse cardiac events, did not differ significantly between both therapeutic strategies: 8.98% for DT vs 8.71% for TT (odds ratio [OR], 1.02; 95% CI, 0.86-1.21). The incidence of hemorrhagic complications was significantly lower in patients treated with DT than TT (13.1% and 21.0%, respectively; OR, 0.57; 95% CI, 0.47-0.70). In over 90% of patients, DT included clopidogrel along with an oral anticoagulant (non-vitamin K antagonist oral anticoagulant or vitamin K antagonist). CONCLUSIONS The results of our meta‑analysis are clearly in line with the current trend of the fastest possible reduction in the use of TT in favor of DT. Almost half lower risk of hemorrhagic complications during DT compared with TT, with similar efficacy of the 2 strategies, provides an argument for the wider use of DT in patients with AF and stent implantation.
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8.
Antithrombotic Treatment in Cryptogenic Stroke Patients With Patent Foramen Ovale: Systematic Review and Meta-Analysis.
Sagris, D, Georgiopoulos, G, Perlepe, K, Pateras, K, Korompoki, E, Makaritsis, K, Vemmos, K, Milionis, H, Ntaios, G
Stroke. 2019;(11):3135-3140
Abstract
Background and Purpose- It is unclear whether treatment with anticoagulants or antiplatelets is the optimal strategy in patients with stroke or transient ischemic attack of undetermined cause and patent foramen ovale that is not percutaneously closed. We aimed to perform a systematic review and meta-analysis of randomized controlled trials to compare anticoagulant or antiplatelet treatment in this population. Methods- We searched PubMed until July 16, 2019 for trials comparing anticoagulants and antiplatelet treatment in patients with stroke/transient ischemic attack and medically treated patent foramen ovale using the terms: "cryptogenic or embolic stroke of undetermined source" and "stroke or cerebrovascular accident or transient ischemic attack" and "patent foramen ovale or patent foramen ovale or paradoxical embolism" and "trial or study" and "antithrombotic or anticoagulant or antiplatelet." The outcomes assessed were stroke recurrence, major bleeding, and the composite end point of stroke recurrence or major bleeding. We used 3 random-effects models: (1) a reference model based on the inverse variance method with the Sidik and Jonkman heterogeneity estimator; (2) a strict model, implementing the Hartung and Knapp method; and (3) a commonly used Bayesian model with a prior that assumes moderate to large between-study variance. Results- Among 112 articles identified in the literature search, 5 randomized controlled trials were included in the meta-analysis (1720 patients, mean follow-up 2.3±0.5 years). Stroke recurrence occurred at a rate of 1.73 per 100 patient-years in anticoagulant-assigned patients and 2.39 in antiplatelet-assigned patients (hazard ratio, 0.68; 95% CI, 0.32-1.48 for the Sidik and Jonkman estimator). Major bleeding occurred at a rate of 1.16 per 100 patient-years in anticoagulant-assigned patients and 0.68 in antiplatelet-assigned patients (hazard ratio, 1.61; 95% CI, 0.72-3.59 for the Sidik and Jonkman estimator). The composite outcome occurred in 52 anticoagulant-assigned and 54 antiplatelet-assigned patients (odds ratio, 1.05; 95% CI, 0.65-1.70 for the Sidik and Jonkman estimator). Conclusions- We cannot exclude a large reduction of stroke recurrence in anticoagulant-assigned patients compared with antiplatelet-assigned, without significant differences in major bleeding. An adequately powered randomized controlled trial of a non-vitamin K antagonist versus aspirin is warranted.
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9.
Prevention of Stroke in Atrial Fibrillation After Coronary Stenting.
Knijnik, L, Rivera, M, Blumer, V, Cardoso, R, Fernandes, A, Fernandes, G, Ferreira, T, Romano, JG, Lambrakos, LK, Cohen, MG
Stroke. 2019;(8):2125-2132
Abstract
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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10.
Long-term antithrombotic treatment in intracranial hemorrhage survivors with atrial fibrillation.
Korompoki, E, Filippidis, FT, Nielsen, PB, Del Giudice, A, Lip, GYH, Kuramatsu, JB, Huttner, HB, Fang, J, Schulman, S, Martí-Fàbregas, J, et al
Neurology. 2017;(7):687-696
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Abstract
OBJECTIVE To perform a systematic review and meta-analysis of studies reporting recurrent intracranial hemorrhage (ICH) and ischemic stroke (IS) in ICH survivors with atrial fibrillation (AF) during long-term follow-up. METHODS A comprehensive literature search including MEDLINE, EMBASE, Cochrane library, clinical trials registry was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We considered studies capturing outcome events (ICH recurrence and IS) for ≥3 months and treatment exposure to vitamin K antagonists (VKAs), antiplatelet agents (APAs), or no antithrombotic medication (no-ATM). Corresponding authors provided aggregate data for IS and ICH recurrence rate between 6 weeks after the event and 1 year of follow-up for each treatment exposure. Meta-analyses of pooled rate ratios (RRs) were conducted with the inverse variance method. RESULTS Seventeen articles met inclusion criteria. Seven observational studies enrolling 2,452 patients were included in the meta-analysis. Pooled RR estimates for IS were lower for VKAs compared to APAs (RR = 0.45, 95% confidence interval [CI] 0.27-0.74, p = 0.002) and no-ATM (RR = 0.47, 95% CI 0.29-0.77, p = 0.002). Pooled RR estimates for ICH recurrence were not significantly increased across treatment groups (VKA vs APA: RR = 1.34, 95% CI 0.79-2.30, p = 0.28; VKA vs no-ATM: RR = 0.93, 95% CI 0.45-1.90, p = 0.84). CONCLUSIONS In observational studies, anticoagulation with VKA is associated with a lower rate of IS than APA or no-ATM without increasing ICH recurrence significantly. A randomized controlled trial is needed to determine the net clinical benefit of anticoagulation in ICH survivors with AF.