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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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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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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.
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Distribution of Estimated 10-Year Risk of Recurrent Vascular Events and Residual Risk in a Secondary Prevention Population.
Kaasenbrood, L, Boekholdt, SM, van der Graaf, Y, Ray, KK, Peters, RJ, Kastelein, JJ, Amarenco, P, LaRosa, JC, Cramer, MJ, Westerink, J, et al
Circulation. 2016;(19):1419-1429
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BACKGROUND Among patients with clinically manifest vascular disease, the risk of recurrent vascular events is likely to vary. We assessed the distribution of estimated 10-year risk of recurrent vascular events in a secondary prevention population. We also estimated the potential risk reduction and residual risk that can be achieved if patients reach guideline-recommended risk factor targets. METHODS The SMART score (Second Manifestations of Arterial Disease) for 10-year risk of myocardial infarction, stroke, or vascular death was applied to 6904 patients with vascular disease. The risk score was externally validated in 18 436 patients with various manifestations of vascular disease from the TNT (Treating to New Targets), IDEAL (Incremental Decrease in End Points Through Aggressive Lipid Lowering), SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol Levels), and CAPRIE (Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events) trials. The residual risk at guideline-recommended targets was estimated by applying relative risk reductions from meta-analyses to the estimated risk for targets for systolic blood pressure, low-density lipoprotein cholesterol, smoking, physical activity, and use of antithrombotic agents. RESULTS The external performance of the SMART risk score was reasonable, apart from overestimation of risk in patients with 10-year risk >40%. In patients with various manifestations of vascular disease, median 10-year risk of a recurrent major vascular event was 17% (interquartile range, 11%-28%), varying from <10% in 18% to >30% in 22% of the patients. If risk factors were at guideline-recommended targets, the residual 10-year risk would be <10% in 47% and >30% in 9% of the patients (median, 11%; interquartile range, 7%-17%). CONCLUSIONS Among patients with vascular disease, there is very substantial variation in estimated 10-year risk of recurrent vascular events. If all modifiable risk factors were at guideline-recommended targets, half of the patients would have a 10-year risk <10%. These data suggest that even with optimal treatment, many patients with vascular disease will remain at >20% and even >30% 10-year risk, clearly delineating an area of substantial unmet medical need.
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Antioxidant and antithrombotic therapies for diabetic kidney disease.
Yan, W, Zhou, B, Shen, Y, Xu, G
Iranian journal of kidney diseases. 2015;(6):413-20
Abstract
With an increasing incidence, diabetic kidney disease (DKD) has been the leading cause of chronic kidney disease and end-stage renal disease, and conventional therapies did not change this situation. This study intended to review and analyze the antioxidant and antithrombotic treatments of DKD for seeking novel therapeutic strategies. Relevant articles involved with antioxidant and antithrombotic treatments in DKD were retrieved and analyzed via systematic assessment. Meta-analysis showed that pancreatic kallikrein definitely reduced glycated hemoglobin in DKD patients (mean difference, 0.36%; 95% confidence interval, 0.08% to 0.63%; P = .01). Apart from the classic agents such as aspirin, novel drugs such as pancreatic kallikrein, sulodexide, and especially the traditional Chinese medicine including Tripterygium wilfordii and lumbrukinase, exert beneficial effects in DKD patients. Antioxidant and antithrombotic treatments are beneficial for DKD patients and represent promising therapeutic strategies in the future.
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Systematic review and network meta-analysis comparing antithrombotic agents for the prevention of stroke and major bleeding in patients with atrial fibrillation.
Cameron, C, Coyle, D, Richter, T, Kelly, S, Gauthier, K, Steiner, S, Carrier, M, Coyle, K, Bai, A, Moulton, K, et al
BMJ open. 2014;(6):e004301
Abstract
OBJECTIVE To examine the comparative efficacy and safety of antithrombotic treatments (apixaban, dabigatran, edoxaban, rivaroxaban and vitamin K antagonists (VKA) at a standard adjusted dose (target international normalised ratio 2.0-3.0), acetylsalicylic acid (ASA), ASA and clopidogrel) for non-valvular atrial fibrillation and among subpopulations. DESIGN Systematic review and network meta-analysis. DATA SOURCES A systematic literature search strategy was designed and carried out using MEDLINE, EMBASE, the Cochrane Register of Controlled Trials and the grey literature including the websites of regulatory agencies and health technology assessment organisations for trials published in English from 1988 to January 2014. ELIGIBILITY CRITERIA FOR SELECTING STUDIES Randomised controlled trials were selected for inclusion if they were published in English, included at least one antithrombotic treatment and involved patients with non-valvular atrial fibrillation eligible to receive anticoagulant therapy. RESULTS For stroke or systemic embolism, dabigatran 150 mg and apixaban twice daily were associated with reductions relative to standard adjusted dose VKA, whereas low-dose ASA and the combination of clopidogrel plus low-dose ASA were associated with increases. Absolute risk reductions ranged from 6 fewer events per 1000 patients treated for dabigatran 150 mg twice daily to 15 more events for clopidogrel plus ASA. For major bleeding, edoxaban 30 mg daily, apixaban, edoxaban 60 mg daily and dabigatran 110 mg twice daily were associated with reductions compared to standard adjusted dose VKA. Absolute risk reductions with these agents ranged from 18 fewer per 1000 patients treated each year for edoxaban 30 mg daily to 24 more for medium dose ASA. CONCLUSIONS Compared with standard adjusted dose VKA, new oral anticoagulants were associated with modest reductions in the absolute risk of stroke and major bleeding. People on antiplatelet drugs experienced more strokes compared with anticoagulant drugs without any reduction in bleeding risk. To fully elucidate the comparative benefits and harms of antithrombotic agents across the various subpopulations, rigorously conducted comparative studies or network meta-regression analyses of patient-level data are required. SYSTEMATIC REVIEW REGISTRATION NUMBER PROSPERO registry-CRD42012002721.
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Antithrombotic agents for preventing thrombosis after infrainguinal arterial bypass surgery.
Geraghty, AJ, Welch, K
The Cochrane database of systematic reviews. 2011;(6):CD000536
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BACKGROUND Peripheral arterial disease (PAD) is frequently treated by either an infrainguinal autologous (using the patient's own veins) or synthetic graft bypass. The rate of occlusion of the graft after one year is between 12% and 60%. To prevent occlusion, patients are treated with an antiplatelet or antithrombotic drug, or a combination of both. Little is known about which drug is optimal to prevent infrainguinal graft occlusion. This is an update of a Cochrane review first published in 2003. OBJECTIVES To evaluate whether antithrombotic treatment improves graft patency, limb salvage and survival in patients with chronic PAD undergoing infrainguinal bypass surgery. SEARCH STRATEGY The Cochrane Peripheral Vascular Diseases Group searched their Specialised Register (last searched August 2010) and the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 3). SELECTION CRITERIA Randomised, controlled trials; two review authors independently assessed the methodological quality of each trial using a standardised checklist. DATA COLLECTION AND ANALYSIS Data collected included patient details, inclusion and exclusion criteria, type of graft, antithrombotic therapy, outcomes, and side effects. MAIN RESULTS A total of 14 trials were included in this review; 4970 patient results were analysed. Four trials evaluating vitamin K antagonists (VKA) versus no VKA suggested that oral anticoagulation may favour autologous venous, but not artificial, graft patency as well as limb salvage and survival. Two other studies comparing VKA with aspirin (ASA) or aspirin and dipyridamole provided evidence to support a positive effect of VKA on the patency of venous but not artificial grafts. Three trials comparing low molecular weight heparin (LMWH) to unfractionated heparin (UFH) failed to demonstrate a significant difference on patency. One trial comparing LMWH with placebo found no significant improvement in graft patency over the first postoperative year in a population receiving aspirin. One trial showed an advantage for LMWH versus aspirin and dipyridamol at one year for patients undergoing limb salvage procedures. Perioperative administration of ancrod showed no greater benefit when compared to unfractionated heparin. Dextran 70 showed similar graft patency rates to LMWH but a significantly higher proportion of patients developed heart failure with dextran. AUTHORS' CONCLUSIONS Patients undergoing infrainguinal venous graft are more likely to benefit from treatment with VKA than platelet inhibitors. Patients receiving an artificial graft benefit from platelet inhibitors (aspirin). However, the evidence is not conclusive. Randomised controlled trials with larger patient numbers are needed in the future to compare antithrombotic therapies with either placebo or antiplatelet therapies.