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Network meta-analysis and trial sequential analysis for atrial fibrillation patients receiving PCI or with ACS.
Yang, SM, Huang, CJ, Chen, CH, Yu, WC, Sung, SH, Guo, CY, Chuang, SY, Cheng, HM, Chiang, CE
Journal of the Chinese Medical Association : JCMA. 2022;(1):59-66
Abstract
BACKGROUND In patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI), choosing the most appropriate antithrombotic treatment remains a dilemma. We aimed to compare the relative efficacy and safety outcomes of antithrombotic drugs in patients with AF after undergoing PCI or ACS. METHODS Randomized controlled trials were systematically searched on PubMed, EMBASE, and the Cochrane Library. Five studies (11,532 patients) were included in the network meta-analysis. Trial sequential analysis (TSA) was performed to assess the reliability and conclusiveness of the meta-analysis comparing the dual antithrombotic therapy strategies with the triple antithrombotic therapy strategy. RESULTS Compared with vitamin K antagonist + dual antiplatelet therapy, novel oral anticoagulant (NOAC) + P2Y12 inhibitor was associated with a significantly better trial-defined primary safety outcome (odds ratio: 0.53; 95% CI, 0.31-0.90) and the lowest probability of thrombolysis in myocardial infarction major bleeding and intracranial hemorrhage using the cumulative ranking technique. In patients omitting aspirin, TSA demonstrated conclusive evidence with significant decreases in all safety outcomes and inconclusive evidence with a nonsignificant increase in in-stent thrombosis (risk ratio: 1.32; TSA-adjusted 95% CI, 0.54-3.24) and myocardial infarction (risk ratio: 1.19; TSA-adjusted 95% CI, 0.84-1.68). CONCLUSIONS In patients with AF receiving PCI or with ACS, NOAC + P2Y12 inhibitor was associated with the lowest bleeding risk but resulted in a statistically nonsignificant, numerically greater risk for stent thrombosis and myocardial infarction, suggesting that triple antithrombotic therapy should still be an option for certain patients at a high risk of stent thrombosis or myocardial infarction.
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Non-Vitamin K Antagonists Versus Warfarin in Patients with Atrial Fibrillation and Bioprosthetic Valves: A Systematic Review and Meta-Analysis.
Cardoso, R, Ternes, CMP, Justino, GB, Fernandes, A, Rocha, AV, Knijnik, L, d'Avila, A, Lopes, RD
The American journal of medicine. 2022;(2):228-234.e1
Abstract
BACKGROUND Patients with atrial fibrillation and bioprosthetic valves are at high risk for thromboembolic events. The pooled efficacy and safety of non-vitamin K oral anticoagulants (NOACs), as a class, relative to warfarin in this population is not well-known. We aimed to compare the efficacy and safety of NOACs relative to warfarin in patients with bioprosthetic valves or valve repair. METHODS We systematically searched EMBASE, PubMed, and Cochrane databases for randomized controlled trials comparing NOACs to warfarin in patients with atrial fibrillation and bioprosthetic valves or valve repair. We pooled outcomes for stroke or systemic embolism, ischemic stroke, hemorrhagic stroke, and major bleeding. RESULTS We included 4 trials with 1379 patients, of whom 723 (52.4%) received a NOAC. Mean follow-up ranged from 90 days to 2.8 years. In the pooled analysis, stroke or systemic embolism was significantly lower in patients treated with NOACs (1.9%) compared with warfarin (3.7%) (odds ratio [OR] 0.43; 95% confidence interval [CI] 0.22-0.85; P = .02). Ischemic stroke (OR 0.72; 95% CI 0.18-2.93), hemorrhagic stroke (OR 0.18; 95% CI 0.03-1.05), cardiovascular death (OR 0.78; 95% CI 0.38-1.62), and all-cause mortality (OR 0.94; 95% CI 0.55-1.62) were not significantly different among groups. Major bleeding was significantly lower in patients treated with NOAC (2.8%) compared with warfarin (4.7%) (OR 0.49; 95% CI 0.28-0.88; P = .02). CONCLUSIONS In patients with atrial fibrillation and bioprosthetic valves or valve repair, NOACs are associated with a reduced incidence of thromboembolic events and major bleeding as compared with warfarin. Thus, NOACs may be considered a preferred option for this patient population.
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Risk of Intracranial Hemorrhage Caused by Direct Oral Anticoagulants for Stroke Prevention in Patients With Atrial Fibrillation (from a Network Meta-Analysis of Randomized Controlled Trials).
Lv, M, Wu, T, Jiang, S, Chen, W, Zhang, J
The American journal of cardiology. 2022;:92-99
Abstract
Patients with atrial fibrillation (AF) who take direct oral anticoagulants (DOACs) face the risk of intracranial hemorrhage (ICH), which can be serious and even life threatening, but the risk of ICH of anticoagulants is still controversial. In this meta-analysis, we compared the risk of ICH between vitamin K antagonists (VKAs) and DOACs. Furthermore, we also compared the risk of ICH in different DOACs. PubMed, Embase, Web of Science, and the Cochrane Library were searched for relevant randomized controlled trials. The outcome was ICH, shown as the odds ratio (OR) with a 95% confidence interval (CI). DOACs were ranked by calculating the surface under the cumulative ranking curve (SUCRA). We included a total of 82,404 patients with AF. DOACs reduced the ICH risk by nearly half compared with VKAs (OR 0.47, 95% CI 0.40 to 0.54, p <0.001). VKAs were the least safe among all oral anticoagulants (SUCRA 1.7). Dabigatran 110 mg was the safest DOAC (SUCRA 87.3) for ICH risk, whereas rivaroxaban 20 mg was a relatively unsafe DOAC (SUCRA 27.5). Compared with rivaroxaban 20 mg, dabigatran 110 mg presented 53% (OR 0.47, 95% CI 0.27 to 0.82) lower relative risk for ICH. In conclusion, DOACs present less ICH risk than VKAs in patients with AF. For patients with AF who are at high risk of ICH, dabigatran 110 mg may be the safest choice among the DOACs.
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Association of Vitamin K and Non-Vitamin K Oral Anticoagulant Use and Cancer Incidence in Atrial Fibrillation Patients.
Iftimi, AA, Rodríguez-Bernal, CL, Peiró, S, Bonanad, S, Ferrero-Gregori, A, Hurtado, I, García-Sempere, A, Sanfélix-Gimeno, G
Clinical pharmacology and therapeutics. 2022;(1):200-208
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Abstract
The association between the use of vitamin K antagonists (VKAs) and cancer risk reduction remains unclear. We aimed to assess the association between the use of VKAs or direct oral anticoagulants (DOACs) and the incidence of cancer in a large cohort of patients with atrial fibrillation (AF) by means of a population-based, propensity-weighted cohort study using population-wide databases including patients diagnosed with nonvalvular AF (NVAF) followed for up of 5 years (median 2.94 years). We created two cohorts based on the initiation therapy (VKA or DOAC). Initiation with VKA or DOAC was defined as filling a prescription with no previous exposure in the preceding 12 months. Cancer diagnoses of any type and for specific tumors (lung, colon, prostate, bladder, and breast). We included 39,989 patients, 31,200 (78.0%) in the VKA cohort. Incidence rate for any cancer was 12.45 per 1,000 person-year in the DOAC cohort vs. 14.55 in the VKA cohort (adjusted hazard ratio (HR): 1.16, 95% confidence interval (CI): 1.02-1.32). In secondary outcomes, no differences were found for specific types of cancer, such as lung (HR: 1.28, CI: 0.89-1.83), colon (HR: 0.84, CI: 0.62-1.13), prostate (HR: 1.40, CI: 0.94-2.10), bladder (HR: 1.07, CI: 0.76-1.52), and breast (HR: 1.05, CI: 0.66-1.69). Sensitivity analyses yielded similar results. Subgroup analyses also produced consistent findings, except for men, for whom VKA was associated with a lower risk of colon cancer (HR: 0.68, 95% CI: 0.48-0.96). Our results do not confirm a chemoprotective effect of VKA when compared with DOAC in a large, real-world cohort of patients with NVAF followed for up to 5 years.
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Direct Current Cardioversion in Atrial Fibrillation Patients on Edoxaban Therapy Versus Vitamin K Antagonists: a Real-world Propensity Score-Matched Study.
Rago, A, Papa, AA, Attena, E, Parisi, V, Golino, P, Nigro, G, Russo, V
Cardiovascular drugs and therapy. 2021;(5):1003-1007
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Abstract
PURPOSE The purpose of the present study was to compare the long-term effectiveness and safety of newly initiated anticoagulation with edoxaban (EDO) versus uninterrupted vitamin K antagonist (VKA) therapy in patients with atrial fibrillation (AF) scheduled for transesophageal echocardiogram (TEE)-guided direct electrical current cardioversion (DCC). METHODS A propensity score-matched cohort observational study was performed comparing the safety and effectiveness of edoxaban versus well-controlled VKA therapy among a cohort of consecutive non-valvular AF patients scheduled for DCC. The primary safety outcome was major bleeding. The primary efficacy outcome was the composite of stroke, transient ischemic attack (TIA), and systemic embolism (SE). FINDINGS A total of 130 AF patients receiving edoxaban 60-mg (EDO) treatment were compared with the same number of VKA recipients. The cumulative incidence of major bleedings was 1.54% in the EDO group and 3.08% in the VKA group (P = 0.4). The cumulative incidence of thromboembolic events was 1.54% in the EDO group and 2.31% in the VKA group (P = 0.9). A non-significant trend in improved adherence was observed between the EDO and VKA groups with a total anticoagulant therapy discontinuation rate of 4.62% (6/130) vs 6.15% (8/130), respectively (P = 0.06). IMPLICATIONS Our study provides the evidence of a safe and effective use of edoxaban in this clinical setting, justified by no significant difference in major bleedings and thromboembolic events between edoxaban and well-controlled VKA treatments.
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Apixaban or Vitamin K Antagonists and Aspirin or Placebo According to Kidney Function in Patients With Atrial Fibrillation After Acute Coronary Syndrome or Percutaneous Coronary Intervention: Insights From the AUGUSTUS Trial.
Hijazi, Z, Alexander, JH, Li, Z, Wojdyla, DM, Mehran, R, Granger, CB, Parkhomenko, A, Bahit, MC, Windecker, S, Aronson, R, et al
Circulation. 2021;(12):1215-1223
Abstract
BACKGROUND In the AUGUSTUS trial (An Open-Label, 2×2 Factorial, Randomized Controlled, Clinical Trial to Evaluate the Safety of Apixaban Versus Vitamin K Antagonist and Aspirin Versus Aspirin Placebo in Patients With Atrial Fibrillation and Acute Coronary Syndrome or Percutaneous Coronary Intervention), apixaban resulted in less bleeding and fewer hospitalizations than vitamin K antagonists, and aspirin caused more bleeding than placebo in patients with atrial fibrillation and acute coronary syndrome or percutaneous coronary intervention treated with a P2Y12 inhibitor. We evaluated the risk-benefit balance of antithrombotic therapy according to kidney function. METHODS In 4456 patients, the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula was used to calculate baseline estimated glomerular filtration rate (eGFR). The effect of apixaban versus vitamin K antagonists and aspirin versus placebo was assessed across kidney function categories by using Cox models. The primary outcome was International Society on Thrombosis and Haemostasis major or clinically relevant nonmajor bleeding. Secondary outcomes included death or hospitalization and ischemic events (death, stroke, myocardial infarction, stent thrombosis [definite or probable], or urgent revascularization). Creatinine clearance <30 mL/min was an exclusion criterion in the AUGUSTUS trial. RESULTS Overall, 30%, 52%, and 19% had an eGFR of >80, >50 to 80, and 30 to 50 mL·min-1·1.73 m-2, respectively. At the 6-month follow-up, a total of 543 primary outcomes of bleeding, 1125 death or hospitalizations, and 282 ischemic events occurred. Compared with vitamin K antagonists, patients assigned apixaban had lower rates for all 3 outcomes across most eGFR categories without significant interaction. The absolute risk reduction with apixaban was most pronounced in those with an eGFR of 30 to 50 mL·min-1·1.73 m-2 for bleeding events with rates of 13.1% versus 21.3% (hazard ratio, 0.59; 95% CI, 0.41-0.84). Patients assigned aspirin had a higher risk of bleeding in all eGFR categories with an even greater increase among those with eGFR >80 mL·min-1·1.73 m-2: 16.6% versus 5.6% (hazard ratio, 3.22; 95% CI, 2.19-4.74; P for interaction=0.007). The risk of death or hospitalization and ischemic events were comparable to aspirin and placebo across eGFR categories with hazard ratios ranging from 0.97 (95% CI, 0.76-1.23) to 1.28 (95% CI, 1.02-1.59) and from 0.75 (95% CI, 0.48-1.17) to 1.34 (95% CI, 0.81-2.22), respectively. CONCLUSIONS The safety and efficacy of apixaban was consistent irrespective of kidney function, compared with warfarin, and in accordance with the overall trial results. The risk of bleeding with aspirin was consistently higher across all kidney function categories. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02415400.
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Clinical risk predictors in atrial fibrillation patients following successful coronary stenting: ENTRUST-AF PCI sub-analysis.
Goette, A, Eckardt, L, Valgimigli, M, Lewalter, T, Laeis, P, Reimitz, PE, Smolnik, R, Zierhut, W, Tijssen, JG, Vranckx, P
Clinical research in cardiology : official journal of the German Cardiac Society. 2021;(6):831-840
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AIMS: This subgroup analysis of the ENTRUST-AF PCI trial (ClinicalTrials.gov Identifier: NCT02866175; Date of registration: August 2016) evaluated type of AF, and CHA2DS2-VASc score parameters as predictors for clinical outcome. METHODS Patients were randomly assigned after percutaneous coronary intervention (PCI) to either edoxaban (60 mg/30 mg once daily [OD]; n = 751) plus a P2Y12 inhibitor for 12 months or a vitamin K antagonist [VKA] (n = 755) plus a P2Y12 inhibitor and aspirin (100 mg OD, for 1-12 months). The primary outcome was a composite of major/clinically relevant non-major bleeding (CRNM) within 12 months. The composite efficacy endpoint consisted of cardiovascular death, stroke, systemic embolic events, myocardial infarction (MI), and definite stent thrombosis. RESULTS Major/CRNM bleeding event rates were 20.7%/year and 25.6%/year with edoxaban and warfarin, respectively (HR [95% CI]: 0.83 [0.654-1.047]). The event rates of composite outcome were 7.26%/year and 6.86%/year, respectively (HR [95% CI]): 1.06 [0.711-1.587]), and of overall net clinical benefit were 12.48%/year and 12.80%/year, respectively (HR [(95% CI]: 0.99 [(0.730; 1.343]). Increasing CHA2DS2-VASc score was associated with increased rates of all outcomes. CHA2DS2-VASc score ≥ 5 was a marker for stent thrombosis. Paroxysmal AF was associated with a higher occurrence of MI (4.87% versus 2.01%, p = 0.0024). CONCLUSION After PCI in AF patients, increasing CHA2DS2-VASc score was associated with increased bleeding rates and CHA2DS2-VASc score (≥ 5) predicted the occurrence of stent thrombosis. Paroxysmal AF was associated with MI. These findings may have important clinical implications in AF patients.
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Trends of Antithrombotic Treatment in Atrial Fibrillation Patients Undergoing Percutaneous Coronary Intervention: Insights from the GReek-AntiPlatElet Atrial Fibrillation (GRAPE-AF) Registry.
Benetou, DR, Varlamos, C, Ktenas, D, Tsiafoutis, I, Koutouzis, M, Bampali, T, Mantis, C, Zarifis, J, Skalidis, E, Aravantinos, D, et al
Cardiovascular drugs and therapy. 2021;(1):11-20
Abstract
PURPOSE Patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) are a high-risk subset of patients, whose optimal antithrombotic treatment strategy, involving a combination of anticoagulant and antiplatelet agents, has not been well defined. Our study aims to investigate contemporary "real-world" trends of antithrombotic treatment strategies in AF patients undergoing PCI, as well as identify factors affecting decision-making at hospital discharge. METHODS "Real-world" data were retrieved from the GReek-AntiPlatElet Atrial Fibrillation (GRAPE-AF) registry, a contemporary, nationwide, multicenter, observational study of AF patients undergoing PCI. Characteristics of patients discharged on triple antithrombotic therapy (TAT) or dual antithrombotic therapy (DAT) were compared in order to identify factors that could influence treatment decisions. RESULTS A total of 654 patients were enrolled (42% with stable coronary artery disease, 58% with acute coronary syndrome). TAT was adopted in 49.9% and DAT in 49.2% of patients at discharge. Regarding anticoagulants, the vast majority of patients (92.9%) received non-vitamin K antagonist oral anticoagulants (NOACs) and only 7.1% received vitamin K antagonists (VKAs). Dyslipidemia, insulin-dependent diabetes mellitus, prior myocardial infarction, acute coronary syndrome at presentation, and regional variations were predictive of TAT adoption, whereas the use of NOACs or ticagrelor was predictive of DAT adoption. CONCLUSION Contemporary "real-world" data concerning antithrombotic treatment in AF patients undergoing PCI indicate a strong shift towards the use of NOACs instead of VKAs, along with a large subset of patients adopting an aspirin-free strategy early after index PCI, with clinical as well as treatment characteristics affecting decision-making. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03362788 (First Posted: December 5, 2017).
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A survey of pathways for mechano-electric coupling in the atria.
Marta Varela, , Roy, A, Lee, J
Progress in biophysics and molecular biology. 2021;:136-145
Abstract
Mechano-electric coupling (MEC) in atrial tissue has received sparse investigation to date, despite the well-known association between chronic atrial dilation and atrial fibrillation (AF). Of note, no fewer than six different mechanisms pertaining to stretch-activated channels, cellular capacitance and geometric effects have been identified in the literature as potential players. In this mini review, we briefly survey each of these pathways to MEC. We then perform computational simulations using single cell and tissue models in presence of various stretch regimes and MEC pathways. This allows us to assess the relative significance of each pathway in determining action potential duration, conduction velocity and rotor stability. For chronic atrial stretch, we find that stretch-induced alterations in membrane capacitance decrease conduction velocity and increase action potential duration, in agreement with experimental findings. In the presence of time-dependent passive atrial stretch, stretch-activated channels play the largest role, leading to after-depolarizations and rotor hypermeandering. These findings suggest that physiological atrial stretches, such as passive stretch during the atrial reservoir phase, may play an important part in the mechanisms of atrial arrhythmogenesis.
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Combination of ablation and left atrial appendage closure as "One-stop" procedure in the treatment of atrial fibrillation: Current status and future perspective.
He, B, Jiang, LS, Hao, ZY, Wang, H, Miao, YT
Pacing and clinical electrophysiology : PACE. 2021;(7):1259-1266
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Atrial fibrillation (AF), the most common arrhythmia, is a major cause of stroke and systemic embolism. Left atrial appendage closure (LAAC) has been proved to be noninferior to traditional Vitamin K antagonists (VKAs) as well as novel oral anticoagulants (NOACs), which is becoming an important alternative to prevent stroke in non-valvular AF. Catheter-based AF ablation (CA) is recommended to be a standard of care in patients with AF refractory to drug therapy due to a better rhythm control and improvement of life quality than antiarrhythmic drugs. Theoretically, the one-stop combination with LAAC and CA tends to bring more benefits in patients with AF, as it not only relieves symptoms, but also reduces the risk of stroke significantly. However, several important questions still need to be considered in the combination procedure although quite a few attempts have already been made in clinical practice. This review provides a comprehensive update on the concept, technique, perioperative management, benefits and other critical issues of the "one-stop" procedure.