ticagrelor and Atrial-Fibrillation

The optimal antithrombotic strategy for patients with a long-term indication for anticoagulation and acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI) remains controversial. This meta-analysis aims to compare randomised trials' outcomes of these patients, focussing on dual versus triple antithrombotic and non vitamin K oral anticoagulants (NOACs) versus vitamin K oral anticoagulants regimens.. Medline, Embase and Cochrane databases were searched from January 1980 to March 2019 yielding 309 articles, and after careful screening, five randomized trials totalling 10 643 patients were included for analysis.. Dual antithrombotic regimens were associated with significantly less thrombolysis in myocardial infarction (TIMI) major and minor bleeding [odds ratio (OR) 0.53, 95% confidence interval (CI) 0.40-0.71], with no significant difference in major adverse cardiovascular events (OR 0.93, 95% CI 0.72-1.22) or all-cause mortality (OR 0.89, 95% CI 0.61-1.19). NOAC regimens had significantly lower TIMI major and minor bleeding (OR 0.58, 95% CI 0.43-0.78) and intracranial bleeding (OR 0.33, 95% CI 0.16-0.66), with similar rates of major adverse cardiovascular events (OR 1.00, 95% CI 0.86-1.16) and all-cause mortality (OR 1.01, 95% CI 0.81-1.26).. Dual antithrombotic and NOAC regimens have reduced bleeding without compromising the risk of cardiovascular events or mortality, and should be preferred for patients with ACS or PCI also needing long-term anticoagulation.

Topics: Acute Coronary Syndrome; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Dabigatran; Drug Therapy, Combination; Dual Anti-Platelet Therapy; Factor Xa Inhibitors; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Stroke; Ticagrelor; Warfarin

Topics: Acute Coronary Syndrome; Adenosine; Administration, Oral; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Hemorrhage; Humans; Morpholines; Percutaneous Coronary Intervention; Piperazines; Platelet Aggregation Inhibitors; Postoperative Complications; Prasugrel Hydrochloride; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Thrombosis; Ticagrelor

About 5%-15% of acute coronary syndrome (ACS) patients undergoing stent implantation have concomitant atrial fibrillation and need both antiplatelet and anticoagulant therapies. The optimal antithrombotic regimen remains uncertain in this scenario.. A multicenter randomized controlled trial (OPtimal management of anTIthroMbotic Agents [OPTIMA]-4) is designed to test the hypothesis that, for ACS patients with concomitant nonvalvular atrial fibrillation (NVAF) and having low-to-moderate risk of bleeding, clopidogrel is comparable in efficacy but superior in safety compared to ticagrelor while being used in combination with dabigatran after new-generation drug-eluting stent (DES) implantation.. ACS patients who have low-to-moderate risk of bleeding (e.g., HAS-BLED score ≤ 2) and require anticoagulation therapy (CHA. The first enrollment occurred on March 12, 2018. The recruitment is anticipated to be completed before December 31, 2024.. The OPTIMA-4 trial offers an opportunity to assess the optimal dual antithrombotic regimen in ACS patients with concomitant NVAF after the implantation of new-generation DES.

Topics: Acute Coronary Syndrome; Aspirin; Atrial Fibrillation; Clopidogrel; Dabigatran; Drug Therapy, Combination; Drug-Eluting Stents; Fibrinolytic Agents; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Ticagrelor

To compare the efficacy and safety of a dual therapy (rivaroxaban and ticagrelor) with a triple therapy (aspirin, clopidogrel and warfarin) in Chinese elderly patients with nonvalvular atrial fibrillation (NVAF) undergoing percutaneous coronary intervention (PCI).. A total of 106 elderly Chinese patients with NAVF after PCI were randomly divided into a dual therapy group treated with ticagrelor 90 mg twice daily and rivaroxaban 15 mg once daily after PCI, and a triple therapy group treated with aspirin 100 mg and clopidogrel 75 mg once daily combined with the dose-adjusted vitamin K antagonist warfarin once daily. The mean follow-up time was 1 year. The primary endpoint was the composite death rate from cardiovascular causes, myocardial infarction, stroke or stent thrombosis. The safety endpoint was clinically significant bleeding (a composite value of major, minor and minimal bleeding).. There were no significant differences between the 2 groups regarding the basic characteristics of the patients. The primary composite endpoint of the dual therapy group after 1 year was not significantly different from the triple therapy group (16.7% vs 15.2%, P = 0.86; HR 1.02; 95% CI: 0.82-1.24), but there was a significant difference in the incidence of hemorrhage (7.4% vs 26.9% P = 0.01; HR 0.71; 95% CI: 0.62-0.83) between the 2 groups.. In elderly Chinese patients with NVAF undergoing PCI, the efficacy of dual (ticagrelor plus rivaroxaban) treatments was comparable to the triple antithrombotic regime (warfarin plus dual antiplatelet therapy). The overall incidence of bleeding was significantly reduced with dual treatment compared to the triple treatment regime.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Coronary Artery Disease; Dabigatran; Drug Therapy, Combination; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Rivaroxaban; Ticagrelor; Treatment Outcome

The REDUAL PCI trial (Evaluation of Dual Therapy With Dabigatran vs Triple Therapy With Warfarin in Patients With AF That Undergo a PCI With Stenting) demonstrated that, in patients with atrial fibrillation following percutaneous coronary intervention, bleeding risk was lower with dabigatran plus clopidogrel or ticagrelor (dual therapy) than warfarin plus clopidogrel or ticagrelor and aspirin (triple therapy). Dual therapy was noninferior for risk of thromboembolic events. Whether these results apply equally to patients at higher risk of ischemic events due to lesion complexity or clinical risk factors is unclear.. The primary end point was time to first major or clinically relevant nonmajor bleeding event. The composite efficacy end point was death, thromboembolic event, or unplanned revascularization. Our prespecified subgroup analysis categorized patients by presence of procedural complexity and/or clinical complexity factors at baseline. A modified dual antiplatelet therapy score categorized patients according to degree of clinical risk.. Of 2725 patients, 43.1% had clinical complexity factors alone, 9.9% procedural factors alone, 10.0% both, and 37.0% neither. Risk of the primary bleeding end point was lower in both dabigatran dual therapy groups than warfarin triple therapy groups, regardless of procedural and/or clinical lesion complexity (interaction. In patients with atrial fibrillation undergoing percutaneous coronary intervention, dabigatran 110 and 150 mg dual therapy reduced bleeding risk compared with warfarin triple therapy, with a similar risk of thromboembolic outcomes, irrespective of procedural and/or clinical complexity and modified dual antiplatelet therapy score. Registration: URL: https://clinicaltrials.gov/; Unique identifier: NCT02164864.

Topics: Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Aspirin; Atrial Fibrillation; Clopidogrel; Coronary Artery Disease; Dabigatran; Dual Anti-Platelet Therapy; Female; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prospective Studies; Risk Assessment; Risk Factors; Stents; Thromboembolism; Ticagrelor; Time Factors; Treatment Outcome; Warfarin

The aim of this study was to assess if prior oral anticoagulant agent (OAC) use modifies the lower bleeding risk observed with dabigatran dual therapy (dabigatran twice daily plus a P2Y. In the RE-DUAL PCI (Randomized Evaluation of Dual Antithrombotic Therapy With Dabigatran Versus Triple Therapy With Warfarin in Patients With Nonvalvular Atrial Fibrillation Undergoing Percutaneous Coronary Intervention) trial, the primary outcome of major bleeding or clinically relevant nonmajor bleeding was lower with dabigatran dual therapy versus warfarin triple therapy in patients with atrial fibrillation who underwent PCI.. A total of 2,725 patients were randomized to dual therapy with dabigatran (110 or 150 mg twice daily) plus clopidogrel or ticagrelor or triple therapy with warfarin plus aspirin and clopidogrel or ticagrelor. Subgroup analysis compared risk for major bleeding or clinically relevant nonmajor bleeding and a composite thromboembolic endpoint in patients with prior OAC use and in those who were OAC treatment naive.. Risk for major bleeding or clinically relevant nonmajor bleeding was reduced with both dabigatran dual therapies compared with warfarin triple therapy in both the prior OAC use group (hazard ratios: 0.58 [95% confidence interval (CI): 0.42 to 0.81] and 0.61 [95% CI: 0.41 to 0.92] with 110 and 150 mg dabigatran, respectively) and the OAC-naive group (hazard ratios: 0.49 [95% CI: 0.38 to 0.63] and 0.76 [95% CI: 0.59 to 0.97] with 110 and 150 mg dabigatran) (p for interaction = 0.42 and 0.37, 110 and 150 mg dabigatran, respectively). The risk for thromboembolic events seemed similar with dabigatran dual therapy (both doses) and warfarin triple therapy across subgroups.. Bleeding risk was reduced with dabigatran dual therapy versus warfarin triple therapy in patients with atrial fibrillation after PCI, regardless of whether they were prior OAC users or OAC treatment naive. These results suggest that it is also safe to switch patients on OAC pre-PCI to dabigatran dual therapy post-PCI.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Coronary Artery Disease; Dabigatran; Drug Substitution; Drug Therapy, Combination; Female; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Risk Factors; Ticagrelor; Time Factors; Treatment Outcome; Warfarin

The aim of this study was to evaluate dabigatran dual therapy versus warfarin triple therapy in patients with or without diabetes mellitus in the RE-DUAL PCI (Randomized Evaluation of Dual Antithrombotic Therapy With Dabigatran Versus Triple Therapy With Warfarin in Patients With Nonvalvular Atrial Fibrillation Undergoing Percutaneous Coronary Intervention) trial.. It is unclear whether dual therapy is as safe and efficacious as triple therapy in patients with atrial fibrillation with diabetes following percutaneous coronary intervention.. In RE-DUAL PCI, 2,725 patients with atrial fibrillation (993 with diabetes) who had undergone PCI were assigned to warfarin triple therapy (warfarin, clopidogrel or ticagrelor, and aspirin) or dabigatran dual therapy (dabigatran 110 mg or 150 mg twice daily and clopidogrel or ticagrelor). Median follow-up was 13 months. The primary outcome was the composite of major bleeding or clinically relevant nonmajor bleeding, and the main efficacy outcome was the composite of death, thromboembolic events, or unplanned revascularization.. Among patients with diabetes, the incidence of major bleeding or clinically relevant nonmajor bleeding was 15.2% in the dabigatran 110 mg dual therapy group versus 27.5% in the warfarin triple therapy group (hazard ratio [HR]: 0.48; 95% confidence interval [CI] 0.35 to 0.67) and 23.8% in the dabigatran 150 mg dual therapy group versus 25.1% in the warfarin triple therapy group (HR: 0.87; 95% CI: 0.62 to 1.22). Risk for major bleeding or clinically relevant nonmajor bleeding was also reduced with both dabigatran doses among patients without diabetes (dabigatran 110 mg dual therapy: HR: 0.54; 95% CI: 0.42 to 0.70; dabigatran 150 mg dual therapy: HR: 0.63; 95% CI: 0.48 to 0.83). Risk for the efficacy endpoint was comparable between treatment groups for both patients with and those without diabetes. No interaction between treatment and diabetes subgroup could be observed, either for bleeding or for composite efficacy endpoints.. In this subgroup analysis, dabigatran dual therapy had a lower risk for bleeding and a comparable rate of the efficacy endpoint compared with warfarin triple therapy in patients with atrial fibrillation with or without diabetes following percutaneous coronary intervention.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Coronary Artery Disease; Dabigatran; Diabetes Mellitus; Drug Substitution; Drug Therapy, Combination; Female; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Risk Factors; Ticagrelor; Time Factors; Treatment Outcome; Warfarin

After percutaneous coronary intervention (PCI) in patients with atrial fibrillation, safety and efficacy with dabigatran dual therapy were evaluated in pre-specified subgroups of patients undergoing PCI due to acute coronary syndrome (ACS) or elective PCI, and those receiving ticagrelor or clopidogrel treatment.. In the RE-DUAL PCI trial, 2725 patients were randomized to dabigatran 110 mg or 150 mg with P2Y12 inhibitor, or warfarin with P2Y12 inhibitor and aspirin. Mean follow-up was 14 months, 50.5% had ACS, and 12% received ticagrelor. The risk of the primary endpoint, major or clinically relevant non-major bleeding event, was reduced with both dabigatran dual therapies vs. warfarin triple therapy in patients with ACS [hazard ratio (95% confidence interval), 0.47 (0.35-0.63) for 110 mg and 0.67 (0.50-0.90) for 150 mg]; elective PCI [0.57 (0.43-0.76) for 110 mg and 0.76 (0.56-1.03) for 150 mg]; receiving ticagrelor [0.46 (0.28-0.76) for 110 mg and 0.59 (0.34-1.04) for 150 mg]; or clopidogrel [0.51 (0.41-0.64) for 110 mg and 0.73 (0.58-0.91) for 150 mg], all interaction P-values >0.10. Overall, dabigatran dual therapy was comparable to warfarin triple therapy for the composite endpoint of death, myocardial infarction, stroke, systemic embolism, or unplanned revascularization, with minor variations across the subgroups, all interaction P-values >0.10.. The benefits of both dabigatran 110 mg and 150 mg dual therapy compared with warfarin triple therapy in reducing bleeding risks were consistent across subgroups of patients with or without ACS, and patients treated with ticagrelor or clopidogrel.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Aspirin; Atrial Fibrillation; Case-Control Studies; Clopidogrel; Coronary Artery Disease; Dabigatran; Drug Therapy, Combination; Dual Anti-Platelet Therapy; Elective Surgical Procedures; Female; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Proportional Hazards Models; Stroke; Ticagrelor; Warfarin

In the RE-DUAL PCI trial of patients with atrial fibrillation (AF) who underwent percutaneous coronary intervention (PCI), dabigatran dual therapy (110 or 150 mg bid, plus clopidogrel or ticagrelor) reduced International Society on Thrombosis and Haemostasis bleeding events compared with warfarin triple therapy, with noninferiority in overall thromboembolic events. This analysis assessed outcomes in relation to patient bleeding and stroke risk profiles, based on the modified HAS-BLED and CHA. The primary endpoint, major bleeding event (MBE) or clinically relevant nonmajor bleeding event (CRNMBE), was compared across study arms in patients categorized by modified HAS-BLED score 0-2 or ≥3. The composite endpoint of death, thromboembolic event, and unplanned revascularization rates was compared in patients categorized by CHA. Risk of MBE or CRNMBE was lower with dabigatran dual therapy (both doses) versus warfarin triple therapy, irrespective of modified HAS-BLED category (treatment-by-subgroup interaction P-value 0.584 and 0.273 for dabigatran 110 and 150 mg dual therapy, respectively, vs warfarin). Risk of the composite thromboembolic endpoint was similar across CHA. Dabigatran dual therapy reduced bleeding events irrespective of bleeding risk category and demonstrated similar efficacy regardless of stroke risk category when compared with warfarin triple therapy.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Clopidogrel; Coronary Artery Disease; Dabigatran; Drug Therapy, Combination; Equivalence Trials as Topic; Female; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Risk Assessment; Stroke; Thromboembolism; Ticagrelor; Warfarin

Triple antithrombotic therapy with warfarin plus two antiplatelet agents is the standard of care after percutaneous coronary intervention (PCI) for patients with atrial fibrillation, but this therapy is associated with a high risk of bleeding.. In this multicenter trial, we randomly assigned 2725 patients with atrial fibrillation who had undergone PCI to triple therapy with warfarin plus a P2Y. The incidence of the primary end point was 15.4% in the 110-mg dual-therapy group as compared with 26.9% in the triple-therapy group (hazard ratio, 0.52; 95% confidence interval [CI], 0.42 to 0.63; P<0.001 for noninferiority; P<0.001 for superiority) and 20.2% in the 150-mg dual-therapy group as compared with 25.7% in the corresponding triple-therapy group, which did not include elderly patients outside the United States (hazard ratio, 0.72; 95% CI, 0.58 to 0.88; P<0.001 for noninferiority). The incidence of the composite efficacy end point was 13.7% in the two dual-therapy groups combined as compared with 13.4% in the triple-therapy group (hazard ratio, 1.04; 95% CI, 0.84 to 1.29; P=0.005 for noninferiority). The rate of serious adverse events did not differ significantly among the groups.. Among patients with atrial fibrillation who had undergone PCI, the risk of bleeding was lower among those who received dual therapy with dabigatran and a P2Y

Topics: Adenosine; Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Dabigatran; Drug Therapy, Combination; Female; Hemorrhage; Humans; Incidence; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Risk; Ticagrelor; Ticlopidine; Warfarin

Long-term oral anticoagulant treatment is obligatory in patients with atrial fibrillation (AF, score of CHA₂DS₂VASc≥2). When these patients undergo percutaneous coronary intervention with a drug-eluting stent (PCI-eS), there is also an indication for aspirin and clopidogrel treatment, according to the ESC Guidelines. However, triple therapy has been known to increase the risk of bleeding complications. Unfortunately, there is little prospective data available to resolve this issue. Therefore, it is imperative that an optimal therapy for AF patients with indications of both anticoagulation and antiplatelet intervention to prevent thrombotic complications without increasing the risk of bleeding is found.. This prospective, randomized, multicenter study is going to assess the hypothesis that in persistent or permanent AF patients (score of CHA₂DS₂VASc≥2) after PCI-eS, the combination therapy of oral anticoagulation (warfarin) and ticagrelor (90 mg/bid) could reduce the risk of bleeding events.. A multicenter, active-controlled, open-label, randomized trial is to be performed to evaluate dual antithrombotic therapy (ticagrelor+warfarin) in persistent or permanent AF patients (score of CHA₂DS₂VASc≥2) after PCI-eS versus the combination of triple antithrombosis (clopidogrel+aspirin+warfarin). The primary endpoint is the overall bleeding up to 6 months, according to TIMI criteria and classifications. The secondary endpoints are the major bleeding events up to 6 months, according to TIMI criteria. The sample size is estimated at 296.. This study is intended to provide information about the safety characteristics of warfarin and ticagrelor in persistent or permanent AF patients after PCI-eS. No prospective randomized study has been conducted on the issue of antithrombotic therapy using warfarin and ticagrelor in these patients. Therefore, the MANJUSRI trial will help to explore and determine a new potential therapeutic regimen for AF patients after PCI-eS.. Clinical Trials.gov # NCT02206815, registered July 30, 2014.

Topics: Adenosine; Adolescent; Adult; Aged; Aspirin; Atrial Fibrillation; Clopidogrel; Drug Therapy, Combination; Drug-Eluting Stents; Female; Fibrinolytic Agents; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Prospective Studies; Research Design; Ticagrelor; Ticlopidine; Warfarin; Young Adult

Optimal antithrombotic strategy for patients with concomitant coronary artery disease and atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) is still controversial, and the role of novel antithrombotic agents has nerve been tested. Therefore, the aim of this study is to evaluate and overall safety and efficacy profile of the combination of rivaroxaban and ticagrelor in this particular population.. The RT-AF study is an open-label, randomized, active-controlled, multicenter clinical trial with up to 420 subjects enrolled in 5 centers. Eligible patients, who have a history or new onset paroxysmal, persistent, or permanent non-valvular AF, referred to the study centers with indications for PCI will be randomly assigned to receive triple therapy (including warfarin, clopidogrel and aspirin) or dual therapy (rivaroxaban and ticagrelor). All subjects will have clinical follow-up at discharge, at 30 days, 6 months and 12 months. The primary end point is major or clinically relevant non-major bleeding events at 12 months. The major secondary end point is the composite efficacy outcome of death, myocardial infarction, stent thrombosis and ischemic stroke.. The study will be sufficiently powered to provide data primarily regarding the safety of dual therapy with rivaroxaban and ticagrelor over the traditional triple therapy in patients with AF undergoing PCI at 12 months. It will also provide important information regarding the efficacy of the two different antithrombotic regimens. (ClinicalTrials.gov identifier: NCT02334254).

Topics: Adenosine; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Coronary Artery Disease; Drug Therapy, Combination; Hemorrhage; Humans; Percutaneous Coronary Intervention; Research Design; Rivaroxaban; Ticagrelor; Ticlopidine; Warfarin

Platelet function testing (PFT) could be a useful clinical tool to guide individualized antithrombotic treatment in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI). We aimed to investigate platelet reactivity (PR) in the context of a contemporary registry. "Real-world" data were retrieved from a nationwide, multicenter, observational study of AF patients on oral anticoagulants (OAC) undergoing PCI. Patients treated with a P2Y

Topics: Anticoagulants; Atrial Fibrillation; Clopidogrel; Fibrinolytic Agents; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Ticagrelor; Treatment Outcome

Patients with atrial fibrillation undergoing coronary intervention are at higher bleeding risk due to the concomitant need for oral anticoagulation and antiplatelet therapy. The RE-DUAL PCI trial demonstrated better safety with dual antithrombotic therapy (DAT: dabigatran 110 or 150 mg b.i.d., clopidogrel or ticagrelor) compared to triple antithrombotic therapy (TAT: warfarin, clopidogrel or ticagrelor, and aspirin). We explored the impact of baseline bleeding risk based on the PRECISE-DAPT score for decision-making regarding DAT vs. TAT.. A score ≥25 points qualified high bleeding risk (HBR). Comparisons were made for the primary safety endpoint International Society of Thrombosis and Haemostasis major or clinically relevant non-major bleeding, and the composite efficacy endpoint of death, thrombo-embolic events, or unplanned revascularization, analysed by time-to-event analysis. PRECISE-DAPT was available in 2336/2725 patients, and 37.9% were HBR. Compared to TAT, DAT with dabigatran 110 mg reduced bleeding risk both in non-HBR [hazard ratio (HR) 0.42, 95% confidence interval (CI) 0.31-0.57] and HBR (HR 0.70, 95% CI 0.52-0.94), with a greater magnitude of benefit among non-HBR (Pint = 0.02). Dual antithrombotic therapy with dabigatran 150 mg vs. TAT reduced bleeding in non-HBR (HR 0.60, 95% CI 0.45-0.80), with a trend toward less benefit in HBR patients (HR 0.92, 95% CI 0.63-1.34; Pint = 0.08). The risk of ischaemic events was similar on DAT with dabigatran (both 110 and 150 mg) vs. TAT in non-HBR and HBR patients (Pint = 0.45 and Pint = 0.56, respectively).. PRECISE-DAPT score appeared useful to identify AF patients undergoing PCI at further increased risk of bleeding complications and may help clinicians identifying the antithrombotic regimen intensity with the best benefit-risk ratio in an individual patient.

Topics: Anticoagulants; Atrial Fibrillation; Clopidogrel; Coronary Artery Disease; Dabigatran; Drug Therapy, Combination; Fibrinolytic Agents; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Ticagrelor

The RE-DUAL PCI trial reported that dabigatran dual therapy (110/150 mg twice daily, plus clopidogrel or ticagrelor) reduced bleeding events versus warfarin triple therapy (warfarin plus aspirin and clopidogrel or ticagrelor) in patients with atrial fibrillation who underwent percutaneous coronary intervention, with noninferiority in composite thromboembolic events. In this prespecified analysis, risks of first major or clinically relevant nonmajor bleeding event and composite end point of death, thromboembolic events, or unplanned revascularization were compared between dabigatran dual therapy and warfarin triple therapy in older (≥ 75 years) and younger (< 75 years) patients, using Cox proportional hazard regression. Of 2,725 patients randomized to treatment, 1,026 (37.7%) were categorized into older and 1,699 (62.3%) into younger age groups. Dabigatran 110 mg dual therapy lowered bleeding risk versus warfarin triple therapy in older (hazard ratio [HR] 0.67; 95% confidence interval [CI] 0.51 to 0.89) and younger patients (HR 0.40; 95% CI 0.30 to 0.54); interaction p value: 0.0125. Dabigatran 150 mg dual therapy lowered bleeding risk versus warfarin triple therapy in younger patients (HR 0.57; 95% CI 0.44 to 0.74), whereas no benefit could be observed in older patients (HR 1.21; 95% CI 0.83 to 1.77); interaction p value: 0.0013. For the thromboembolic end point, there was a trend for a higher risk with dabigatran 110 mg dual therapy in older patients, compared with warfarin triple therapy, whereas the risk was similar in younger patients. For dabigatran 150 mg dual therapy, the thromboembolic risk versus warfarin triple therapy was similar in older and younger patients. In conclusion, the benefits of dabigatran dual therapy differed in the 2 age groups, which may help dose selection when using dabigatran dual therapy.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Coronary Artery Disease; Dabigatran; Drug Therapy, Combination; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Revascularization; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Proportional Hazards Models; Stroke; Thromboembolism; Ticagrelor; Treatment Outcome; Warfarin

Ticagrelor is a drug widely used in patients with acute coronary syndromes (ACS) that specifically increases the plasma level of adenosine, which is likely to cause atrial fibrillation (AF). Therefore, in this study we aimed to investigate the electrocardiographic and echocardiographic predictors of AF development after P2Y12 receptor antagonists in ACS patients.. This cross-sectional study included 831 patients with ACS (486 [58.5%] with ST elevated myocardial infarction [STEMI] and 345 [41.5%] with non-ST elevated myocardial infarction [NSTEMI]). Patients were divided into ticagrelor (n = 410) and clopidogrel (n = 421) groups. P wave properties including P wave dispersion and atrial electromechanical conduction properties were measured as AF predictors with surface ECG and tissue Doppler imaging.. Baseline characteristics such as age, sex, heart rate, blood pressure, and laboratory parameters were almost the same in the ticagrelor and clopidogrel groups. The statistical analysis showed no significant difference in P wave dispersion (PWD) between ticagrelor and clopidogrel groups (40.98 ± 12 ms versus 40.06 ± 12 ms, P = 0.304). Subgroups analysis according to ACS types also showed no significant difference in PWD (NSTEMI: 41.16 ± 13.8 ms versus 40.76 ± 13.55 ms, P = 0.799; STEMI: 40.9 ± 12.62 ms versus 39.19 ± 11.18 ms, P = 0.132). In addition, we did not find significant difference in atrial electromechanical delay (EMD) with tissue Doppler imaging (interatrial EMD 24.11 ± 3.06 ms versus 24.46 ± 3.23 ms, P = 0.279).. In conclusion, we did not find any difference in detailed electrocardiographic and echocardiographic parameters as AF predictors between ticagrelor and clopidogrel groups in patients with ACS

Topics: Acute Coronary Syndrome; Atrial Fibrillation; Clopidogrel; Cross-Sectional Studies; Echocardiography, Doppler; Electrocardiography; Female; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Risk Factors; ST Elevation Myocardial Infarction; Ticagrelor

Topics: Acute Coronary Syndrome; Atrial Fibrillation; Clopidogrel; Dabigatran; Humans; Percutaneous Coronary Intervention; Ticagrelor

Oral anticoagulation is considered standard therapy for stroke prevention in atrial fibrillation (AF). Endocardial activation triggers expression of pro-thrombotic mediators including tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1), and contributes to thrombus formation in the left atrial appendage (LAA) of AF patients. Recently, pleiotropic effects of specific P2Y12 receptor antagonists were demonstrated; however, whether these drugs possess antithrombotic effects on LAA endocardial cells currently remains unknown.. LAA were obtained from 14 patients with known AF undergoing elective cardiac surgery including LAA removal at the University Hospital Zurich. LAA endocardial cells were isolated and pre-incubated with ticagrelor (10-7, 10-6, 10-5M) or clopidogrel active metabolite (CAM) (1.5 × 10-8, 1.5 × 10-7, 1.5 × 10-6 M) before stimulation with tumour necrosis factor-alpha (TNF-α) (10 ng/mL). Finally, TF and PAI-1 expression and activity were analysed. Ticagrelor, unlike CAM, concentration dependently decreased TNF-α-induced TF expression and TF activity in LAA endocardial cells. Further, ticagrelor, but not CAM reduced PAI-1 expression and enzyme activity in TNF-α-stimulated LAA endocardial cells. In contrast, TF pathway inhibitor (TFPI) remained unaffected by both dugs.. Ticagrelor, but not CAM, reduces expression and activity of TF and PAI-1 in LAA endocardial cells isolated from patients with AF, indicating possible local antithrombotic effects. Such pleiotropic properties of ticagrelor may contribute to a reduction in thromboembolic complications in patients with AF.

Topics: Adenosine; Antithrombins; Atrial Appendage; Atrial Fibrillation; Clopidogrel; Endocardium; Heart Atria; Humans; Plasminogen Activator Inhibitor 1; Purinergic P2Y Receptor Antagonists; Thromboplastin; Ticagrelor; Ticlopidine; Tumor Necrosis Factor-alpha

Topics: Adenosine; Aged; Angina, Unstable; Atrial Fibrillation; Clopidogrel; Humans; Male; Ticagrelor; Ticlopidine; Treatment Outcome

Treatment with warfarin in combination with clopidogrel has been shown to reduce the incidence of major bleeding as compared to triple antithrombotic therapy (TT; warfarin, clopidogrel and aspirin). However, there are uncertainties regarding the risk for thrombosis since poor-responsiveness to clopidogrel is common. Ticagrelor is a more potent platelet inhibitor, but data supporting concurrent use of ticagrelor and warfarin (dual antithrombotic therapy, DT) is limited. This study therefore sought to evaluate the risk of bleeding and thrombosis associated with DT after an acute coronary syndrome (ACS).. We identified all ACS patients on DT upon discharge from Helsingborg Hospital and Skåne University Hospital in Malmö and Lund, Sweden, during 2013. Patients on DT were compared with historical controls discharged with TT. Major bleeding was defined in accordance with the HAS-BLED derivation study. Patients were retrospectively followed for three months.. In total, 107 DT patients were identified and compared with 159 controls on TT. Mean HAS-BLED bleeding risk score and duration of treatment were similar between the groups (HAS-BLED 2.2+/-0.8 vs 2.2+/-1.0 units, p=NS; duration 2.7+/-0.8 vs 2.5+/-0.9months, p=NS; DT vs TT). The incidence of spontaneous major bleeding was similar between the groups, as was a composite of all thrombotic events, i.e. peripheral embolism, stroke/TIA and acute coronary syndrome (bleeding 8/106 (7.5%) vs 11/157 (7.0%), p=NS; thrombosis 5/106 (4.7%) vs 5/157 (3.2%), p=NS; DT vs TT).. Rates of thrombotic and bleeding events were similar in patients with TT and patients with ticagrelor and warfarin.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Aged, 80 and over; Aspirin; Atrial Fibrillation; Clopidogrel; Drug Therapy, Combination; Female; Fibrinolytic Agents; Hemorrhage; Humans; Male; Middle Aged; Retrospective Studies; Risk Factors; Thrombosis; Ticagrelor; Ticlopidine; Treatment Outcome; Warfarin

Topics: Adenosine; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Cardiovascular Diseases; Clopidogrel; Dabigatran; Fibrinolytic Agents; Guideline Adherence; Humans; Morpholines; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Thromboembolism; Ticagrelor; Ticlopidine; Treatment Outcome

Topics: Acute Coronary Syndrome; Adenosine; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Female; Humans; Male; Platelet Aggregation Inhibitors; Ticagrelor; Warfarin