Anticoagulant Monotherapy Research Articles

Oral anticoagulant (OAC) monotherapy vs. dual-antithrombotic therapy (DAT) in patients with atrial fibrillation and coronary artery disease; a meta-analysis of four randomized controlled trials

Background: Dual-antithrombotic therapy (DAT) is recommended for patients with atrial fibrillation (AF) and stable coronary artery disease (CAD) but carries an increased risk of bleeding. Recent trials suggest oral anticoagulant (OAC) monotherapy as a safer alternative, but data remains limited. We conducted a meta-analysis to compare OAC monotherapy with DAT in this population. Methods: A comprehensive literature search was conducted using PubMed, Embase, and Cochrane Central Library to identify randomized controlled trials (RCTs) that compared OAC monotherapy with DAT in patients with AF and stable CAD. A bivariate random-effects model was used to perform meta-analyses. Statistical analyses were conducted using R Software 4.4.1, with a significance level of P < 0.05. Heterogeneity was assessed using I 2 statistics, and the quality of studies was evaluated using the revised Cochrane risk-of-bias tool. Results: Four RCTs with a total of 4123 patients (20.2% females) were included. The mean age of the participants was 74 years. The results showed a significant reduction in major or clinically relevant nonmajor bleeding (risk ratio [RR]: 0.52; 95% confidence interval [CI]: 0.34–0.80; P = 0.003) in the OAC monotherapy group compared to the DAT group. However, net adverse clinical events (NACE) (RR: 0.67; 95% CI: 0.45–1.01; P = 0.054), major ischemic events (RR: 0.98; 95% CI: 0.62–1.53; P = 0.91) and all-cause mortality (RR: 0.94; 95% CI: 0.49–1.83; P = 0.87) were comparable between the two groups. Conclusions: In patients with AF and stable CAD, OAC monotherapy reduced the risk of major bleeding, with no significant differences in NACE, major ischemic events, or all-cause mortality as compared to DAT.

Comparative Analysis of Anticoagulation Versus Combination Anticoagulation and Antiplatelet Therapy in Atrial Fibrillation Patients Presenting With Gastrointestinal Bleeding.

Patients with atrial fibrillation (AF) taking antithrombotic (AT) therapy are at an increased risk of gastrointestinal bleeding (GIB). The comparative effect of a combination of anticoagulant (AC) and antiplatelet (AP) versus AC monotherapy on clinical outcomes in patients with AF presenting with GIB is not well characterized. This study compares outcomes in AF patients with GIB on AC alone with those on combination AP and AC therapy, as part of a larger prospective study from 2013 to 2023. One hundred and thirty-seven patients diagnosed with AF who presented with overt GIB were evaluated during their hospitalization, at 1 month and 1 year postdischarge and then annually. The median follow-up of patients was 57 months. Patients in the combination AP + AC therapy group had a higher prevalence of coronary artery disease, myocardial infarction, and coronary/vascular stent placement compared with the AC monotherapy group. No statistically significant differences were noted between the 2 groups in terms of end-of-follow-up mortality, in-hospital mortality, major bleeding, rebleeding, and length of hospital stay. Cox regression analysis revealed chronic kidney disease [hazard ratio (HR) 2.05, 95% confidence interval (1.04-4.05) ( P = 0.038)] and warfarin use [HR 4.94, 95% confidence interval (1.11-22.09) ( P = 0.037)] to be independent predictors of mortality at 12 months. Antithrombotic therapy in patients with AF who experience GIB should be mainly directed by their cardiovascular needs. Health care providers may explore non-vitamin K antagonist oral anticoagulants as alternatives to warfarin for AF patients at risk of GIB, and efforts must be maximized to prevent bleeding in patients with chronic kidney disease.

Anticoagulant monotherapy versus anticoagulant therapy in combination with single antiplatelet agent in patients after coronary artery bypass grafting - analysis of real-world data

Abstract Introduction Among patients undergoing coronary artery bypass grafting (CABG), in a significant group chronic anticoagulant treatment is indicated. Current recommendations from scientific societies do not clearly indicate the optimal antithrombotic treatment strategy in this group of patients. Addition of antiplatelet therapy recommended after CABG to chronic anticoagulant therapy increases the risk of bleeding complications, however, efficacy of antithrombotic treatment strategies has not been compared in large prospective studies. Purpose The aim of the study was to compare the efficacy and safety of post-CABG antithrombotic treatment strategies in patients after CABG with coexisting indications for chronic anticoagulant treatment, based on the analysis of the real-world database. Methods Real-world data from the THIN database were analyzed. The population included adult patients from France and Great Britain undergoing CABG between 2010 and 2022 who were treated with anticoagulants within a year after CABG and who were followed for at least one year after CABG or until death. The endpoints were compared between groups of patients treated with anticoagulants in monotherapy (VKA or NOAC) (MT) and patients treated with anticoagulants (VKA or NOAC) in combination with antiplatelet agent (ASA or oral P2Y12 inhibitor) (CT). The primary efficacy endpoint was the occurrence of major adverse cardiac events (MACE), the primary safety endpoint was major bleeding and the secondary safety endpoint was death from any cause. Results A database query obtained records of 3500 patients meeting the inclusion criteria, but due to missing data, 710 patients were included in the analysis. In this group, 193 (27.2%) patients were in MT group, and 517 (72.8%) in CT group. The majority (87.0%) were men, the mean age was 72.8 (9.4) years. The MACE occurred in 19.2% patients in the MT and in 19.3% in the CT. There was no significant effect of antithrombotic treatment strategy on time to event (log-rank test p=0.553) and on risk of MACE occurrence (HR 0.89 (95% CI 0.61 - 1.31) for CT vs. MT). The major bleeding occurred in 6.2% patients in the MT and in 10.3% in the CT and no significant effect of group was observed (log-rank test p=0.170, HR 1.55 [95% CI 0.83 - 2.90] for CT vs. MT). The death from any cause occurred in 10.9% patients in the MT and in 10.1% in the CT and no significant effect of group was observed (log-rank test p=0.174, HR 0.70 [95% CI 0.42 - 1.17] for CT vs. MT). Conclusions The results indicate the comparable efficacy and safety of both antithrombotic treatment strategies: anticoagulants in monotherapy versus anticoagulants in combination with antiplatelet agent in the group of patients after CABG with coexisting indications for chronic anticoagulation.

Optimal antithrombotic therapy in ischemic stroke patients with non-valvular atrial fibrillation and atherothrombosis: study protocol for a randomized controlled trial.

The addition of antiplatelet therapy to anticoagulant therapy in patients with stroke with non-valvular atrial fibrillation (NVAF) and atherothrombotic disease may increase bleeding risk without reducing recurrent stroke risk. To evaluate the clinical benefits of anticoagulant monotherapy compared to combination therapy with anticoagulants and antiplatelet agents. This is an investigator-initiated prospective multicenter, randomized, open-label, parallel-group clinical trial. Patients with NVAF and atherothrombotic disease who have had a recent ischemic stroke or transient ischemic attack will be eligible to participate in this trial. The primary outcome is a composite of ischemic cardiovascular events, including cardiovascular death, ischemic stroke, myocardial infarction, systemic embolism, ischemic events requiring urgent revascularization, and major bleeding events within 2 years after randomization. This study will enroll 400 patients, 200 receiving anticoagulant monotherapy and 200 receiving combination therapy. This sample size will provide 90% power (one-sided p = 0.025) to detect a risk reduction in outcome events within 2 years, assuming event rates of 13 and 27% for each group, respectively, and a 10% loss to follow-up at a 2.5% significance level with one-sided log-rank tests at an interim analysis and a final analysis. This will be the first study to assess the net clinical benefit of oral anticoagulant monotherapy in ischemic stroke patients with NVAF and atherothrombosis. https://clinicaltrials.gov/study/NCT03062319, NCT03062319; https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000029222, UMIN000025392; https://jrct.niph.go.jp/latest-detail/jRCTs051180202, jRCTs051180202.

Evaluation of Long-term Antithrombotic Management for Atrial Fibrillation Patients with a History of Coronary Stent Implantation

Purpose: American expert consensus publications recommend discontinuation of antiplatelet agents 6 to 12 months after Percutaneous Coronary Intervention (PCI) in patients with Atrial Fibrillation (AF) who require chronic anticoagulation, and use of oral anticoagulant monotherapy thereafter. This study aimed to assess real-world long-term antithrombotic therapy management practices and factors associated with the continuation of antiplatelet agents past 12 months post-PCI in patients with AF requiring chronic anticoagulation. Methods: Patients with AF and a history of PCI greater than 12 months before their most recent encounter with physicians at an outpatient electrophysiology clinic were identified by chart review. Patient demographics, clinical characteristics, and current antithrombotic regimen were collected from encounters that occurred between July 2019 and June 2022. The independent predictive factors associated with the continuation of antiplatelet agents were identified using univariate and regression analyses. Results: Out of 66 patients, 67% continued antiplatelet therapy for greater than 12 months post-PCI. Patients on antiplatelets were significantly less likely to have bare metal stents (p = 0.006), be greater than five years post-PCI (p = 0.002), and have a HASBLED score of two or less (p = 0.028) when compared to patients on oral anticoagulant monotherapy. Bare metal stent history (p = 0.045) and HASBLED score of two or less (p = 0.016) were also significant in regression analysis. Conclusion: This study found that most patients with AF and a history of PCI continued antiplatelet therapy longer than 12 months post-PCI, often despite the high bleeding risk.

Risk Factors for Treatment Transition in Patients with Low-Risk Atrial Fibrillation Patients Undergoing Anticoagulation Monotherapy: A Large Claims Database Study in Japan

The global prevalence of atrial fibrillation (AF) is rising, paralleling increased life expectancy. Early rhythm control benefits AF management. However, in low-risk, often asymptomatic, AF patients, anticoagulant monotherapy is the selected treatment, aligning with current guidelines. However, early AF progression in these low-risk individuals is not well-understood. Thus, this study aims to: 1) determine the proportion of low-risk AF patients who worsen within a year of initial AF diagnosis and 2) identify risk factors such treatment transitions. We analyzed data from 18623 AF patients, spanning January 2005 to June 2017. Low-risk patients were those on anticoagulant monotherapy ± rate control, following the JCS/JHRS 2020 Guideline on Pharmacotherapy of Cardiac Arrhythmias. We defined 2 patterns of treatment transition for 1) initiating ablation or antiarrhythmic drug therapy and 2) solely using antiarrhythmic drugs. This retrospective cohort study was employed a 12-month study, following a 6-month screening period. We included 1874 patients for all rhythm control (analysis 1) and 1503 for only medication-based control (analysis 2). The primary endpoint, treatment transition of AF under monotherapy, occurred in 28.4% of patients in analysis 1 and 10.8% in analysis 2. Risk factors common to both scenarios were male gender, baseline rate control drug use, and rivaroxaban selection, as identified by multiple logistic regression. These findings suggest a higher AF treatment transition trend in patients starting rivaroxaban, calling for further research. The study highlights the importance of informed early rhythm control initiation decisions in clinical settings.

Dual Antithrombotic Therapy versus Anticoagulant Monotherapy for Major Adverse Limb Events in Patients with Concomitant Lower Extremity Arterial Disease and Atrial Fibrillation: A Propensity Score Weighted Analysis

Patients with symptomatic lower extremity arterial disease (LEAD) are recommended to receive antiplatelet therapy, while direct oral anticoagulants (DOACs) are standard for stroke prevention in patients with atrial fibrillation (AF). For patients with concomitant LEAD and AF, data comparing dual antithrombotic therapy (an antiplatelet agent used in conjunction with a DOAC) vs. DOAC monotherapy are scarce. This retrospective cohort study, based on data from the Taiwan National Health Insurance Research Database, aimed to compare the efficacy and safety of these antithrombotic strategies. Patients with AF who underwent revascularisation for LEAD between 2012 - 2020 and received any DOAC within 30 days of discharge were included. Patients were grouped by antiplatelet agent exposure into the dual antithrombotic therapy and DOAC monotherapy groups. Inverse probability of treatment weighting was used to mitigate selection bias. Major adverse limb events (MALEs), ischaemic stroke or systemic embolism, and bleeding outcomes were compared. Patients were followed until the occurrence of any study outcome, death, or up to two years. A total of 1 470 patients were identified, with 736 in the dual antithrombotic therapy group and 734 in the DOAC monotherapy group. Among them, 1 346 patients received endovascular therapy as the index revascularisation procedure and 124 underwent bypass surgery. At two years, dual antithrombotic therapy was associated with a higher risk of MALEs than DOAC monotherapy (subdistribution hazard ratio [SHR] 1.34, 95% confidence interval [CI] 1.15 - 1.56), primarily driven by increased repeat revascularisation. Dual antithrombotic therapy was also associated with a higher risk of major bleeding (SHR 1.43, 95% CI 1.05 - 1.94) and gastrointestinal bleeding (SHR 2.17, 95% CI 1.42 - 3.33) than DOAC monotherapy. In patients with concomitant LEAD and AF who underwent peripheral revascularisation, DOAC monotherapy was associated with a lower risk of MALEs and bleeding events than dual antithrombotic therapy.

Real-World Bleeding Risk of Anticoagulant and Nonsteroidal Anti-inflammatory Drugs Combotherapy versus Anticoagulant Monotherapy.

The incidence of acute gastrointestinal bleeding (GIB) increases with the utilization of anticoagulant and nonsteroidal anti-inflammatory drugs (NSAIDs). This study aimed to compare the risk of GIB between anticoagulant and NSAIDs combotherapy and anticoagulant monotherapy in real-world practice. We investigated the relative risk of GIB in individuals newly prescribed anticoagulant and NSAIDs combination therapy and that in individuals newly prescribed anticoagulant monotherapy at three hospitals using "common data model." Cox proportional hazard models and Kaplan-Meier estimation were employed for risk comparison after propensity score matching. A comprehensive analysis of 2,951 matched pairs showed that patients who received anticoagulant and NSAIDs combousers exhibited a significantly higher risk of GIB than those who received anticoagulant monousers (hazard ratio [HR], 1.66; 95% confidence interval [CI], 1.30 to 2.12; p<0.001). The risk of GIB associated with anticoagulant and NSAIDs combination therapy was also significantly higher than that associated with anticoagulant monotherapy in patients aged >65 years (HR, 1.53; 95% CI, 1.15 to 2.03; p=0.003) and >75 years (HR, 1.89; 95% CI, 1.23 to 2.90; p=0.003). We also found that the risk of GIB was significantly higher in the patients who received anticoagulant and NSAIDs combousers than that in patients who received anticoagulant monousers in both male (p=0.016) and female cohorts (p=0.010). The risk of GIB is significantly higher in patients who receive anticoagulant and NSAIDs combotherapy than that in patients who receive anticoagulant monotherapy. In addition, the risk of GIB associated with anticoagulant and NSAIDs combotherapy was much higher in individuals aged >75 years. Therefore, physicians should be more aware of pay more attention to the risk of GIB when they prescribe anticoagulant and NSAIDs.

The optimal antithrombotic strategy for post-stroke patients with atrial fibrillation and extracranial artery stenosis—a nationwide cohort study

BackgroundIn post-stroke atrial fibrillation (AF) patients who have indications for both oral anticoagulant (OAC) and antiplatelet agent (AP), e.g., those with carotid artery stenosis, there is debate over the best antithrombotic strategy. We aimed to compare the risks of ischemic stroke, composite of ischemic stroke/major bleeding and composite of ischemic stroke/intracranial hemorrhage (ICH) between different antithrombotic strategies.MethodsThis study included post-stroke AF patients with and without extracranial artery stenosis (ECAS) (n = 6390 and 28,093, respectively) identified from the Taiwan National Health Insurance Research Database. Risks of clinical outcomes and net clinical benefit (NCB) with different antithrombotic strategies were compared to AP alone.ResultsThe risk of recurrent ischemic stroke was higher for patients with ECAS than those without (12.72%/yr versus 10.60/yr; adjusted hazard ratio [aHR] 1.104, 95% confidence interval [CI] 1.052–1.158, p < 0.001). For patients with ECAS, when compared to AP only, non-vitamin K antagonist oral anticoagulant (NOAC) monotherapy was associated with lower risks for ischaemic stroke (aHR 0.551, 95% CI 0.454—0.669), the composite of ischaemic stroke/major bleeding (aHR 0.626, 95% CI 0.529—0.741) and the composite of ischaemic stroke/ICH (aHR 0.577, 95% CI 0.478—0.697), with non-significant difference for major bleeding and ICH. When compared to AP only, warfarin monotherapy was associated with higher risks of major bleeding (aHR 1.521, 95% CI 1.231—1.880), ICH (aHR 2.045, 95% CI 1.329—3.148), and the composite of ischaemic stroke and major bleeding. With combination of AP plus warfarin, there was an increase in ischaemic stroke, major bleeding, and the composite outcomes, when compared to AP only. NOAC monotherapy was the only approach associated with a positive NCB, while all other options (warfarin, combination of AP-OAC) were associated with negative NCB.ConclusionsFor post-stroke AF patients with ECAS, NOAC monotherapy was associated with lower risks of adverse outcomes and a positive NCB. Combination of AP with NOAC or warfarin did not offer any benefit, but more bleeding especially with AP-warfarin combination therapy.

Optimal antithrombotic strategy in patients with atrial fibrillation beyond 1 year after drug-eluting stent implantation: Design and rationale of the randomized ADAPT AF-DES trial

BackgroundBoth anticoagulation and antiplatelet therapies are recommended after percutaneous coronary intervention (PCI) in patients with atrial fibrillation (AF). Although contemporary guidelines recommend discontinuation of antiplatelet therapy 1 year after drug-eluting stent (DES) implantation due to excessive bleeding risk, supporting randomized trials are still lacking. MethodsThe ADAPT AF-DES trial is a multicenter, prospective, open-label, randomized, non-inferiority trial, enrolling 960 patients with AF with a CHA2DS2-VASc score > 1, who underwent PCI with DES implantation at least 12 months before enrollment. Eligible patients are randomly assigned to receive either non-vitamin K antagonist oral anticoagulant (NOAC) monotherapy or NOAC plus clopidogrel combination therapy. The primary outcome is net adverse clinical event (NACE) at 1 year after randomization, defined as a composite of all-cause death, myocardial infarction, stent thrombosis, stroke, systemic embolism, and major or clinically relevant non-major bleeding, as defined by the International Society on Thrombosis and Hemostasis criteria. We hypothesize that NOAC monotherapy would be non-inferior to NOAC plus clopidogrel combination therapy for NACE in patients with AF beyond 12 months after DES implantation. ConclusionsThe ADAPT AF-DES trial will evaluate the efficacy and safety of NOAC monotherapy versus NOAC plus clopidogrel combination therapy in patients with AF beyond 12 months after PCI with DES implantation. The ADAPT AF-DES trial will provide robust evidence for an optimal antithrombotic strategy in patients with AF after DES implantation. Clinical trial registrationhttps://www.clinicaltrials.gov. Unique identifier: NCT04250116.

Comparison of direct oral anticoagulants and warfarin in chronic limb-threatening ischemia

ObjectiveThe role of direct oral anticoagulants (DOACs) in chronic limb-threatening ischemia after revascularization is unknown. Current evidence-based guidelines do not provide clear guidance on the role of anticoagulation or the selection of anticoagulant. Current practice is highly varied and based on provider and patient preference. The purpose of this study was to measure the impact of different anticoagulants on the incidence of major adverse limb events (MALEs) after revascularization for chronic limb-threatening ischemia, major adverse cardiovascular events (MACEs), all-cause mortality, and hospitalization for major bleeding events. MethodsThis was a single-center, observational, retrospective cohort study. Subjects were eligible if they were 18 years or older; underwent endovascular or open revascularization for chronic limb-threatening ischemia, rest pain, or tissue loss; and were subsequently prescribed apixaban, rivaroxaban, or warfarin. The primary end point was the incidence of MALEs, including above-ankle amputation or major index-limb reintervention, within 1 year of index event. Secondary end points included the rate of all-cause mortality, MACEs, and incidence of International Society on Thrombosis and Haemostasis (ISTH) major bleeding. ResultsFrom January 1, 2017, to September 20, 2022, 141 patients met the inclusion and exclusion criteria and were reviewed. The median age was 67 years, with 92 patients prescribed apixaban or rivaroxaban and 49 patients prescribed warfarin. Of these, 42 patients were prescribed triple antithrombotic therapy, 88 dual antithrombotic therapy, and 13 anticoagulant monotherapy. The primary outcome of 1-year MALEs occurred in 36.7% of the warfarin group and 33.7% of the DOAC group (relative risk [RR], 1.09; 95% CI, 0.53-2.25; P = .72). Secondary outcomes of 1-year MACEs (10.2% vs 4.3%; RR, 2.35; 95% CI, 0.60-9.18; P = .18) and 1-year all-cause mortality (26.5% vs 16.3%; RR, 1.63; 95% CI, 0.70-3.78; P = .15) did not differ between the groups. The secondary safety outcome of 1-year ISTH major bleeding occurred in 16.3% of the warfarin group and 4.3% of the DOAC group (RR, 3.76; 95% CI, 1.07-13.19; P = .015). ConclusionsIn patients with chronic limb-threatening ischemia who were revascularized and prescribed anticoagulation with apixaban, rivaroxaban, or warfarin on discharge, no difference in MALEs, MACEs, or all-cause mortality was found. However, 1-year admissions for ISTH major bleeding were significantly higher among patients prescribed warfarin. A randomized trial may confirm these findings.

Spontaneous and stimulated platelet aggregation activity in patients with atrial fibrillation and thrombotic complications

Aim: To study spontaneous and stimulated by adenosine diphosphate (ADP), adrenaline and collagen platelet aggregation activity, CD40-CD40 ligand system in patients with atrial fibrillation (AF) with previous thromboembolic complications (TEC) and newly diagnosed thrombosis.Material and Methods. The study included patients with «non-valvular» AF and anamnesis of TEC and newly identified thrombosis on anticoagulants in the period 01.2020-01.2023: 13 patients had anamnesis of TEC (group 1), in 18 patients were initially diagnosed thrombosis/spontaneous atrial echocontrast of high grade (group 2). The comparison group was the healthy individuals (n = 31) (group 3). The spontaneous aggregation ability of platelets and stimulated with solutions of ADP, adrenaline and collagen, the level of CD40 markers, soluble CD40 ligand (CD40L) were studied.Results. The spontaneous platelet aggregation activity was significantly higher in patients of group 2 compared with healthy individuals with a formation trend of larger aggregates in patients with TEC. When aggregation was induced by collagen, the rate of aggregate formation was significantly lower in the 1st and 2nd groups compared with healthy individuals. When using ADP, a comparable decrease in the degree and speed was noted, and when using adrenaline, only the rate of platelet aggregation was observed in groups 1 and 2. The concentration of soluble CD40L was significantly higher in patients with a history of TEC and newly thrombosis.Conclusion. Spontaneous platelet aggregation activity and the concentration of soluble CD40L are increased both in patients with past of TEC and in patients with newly diagnosed thrombosis due to AF and anticoagulant monotherapy.

Optimal Antithrombotic Therapy Beyond 1-Year After Coronary Revascularization in Patients With Atrial Fibrillation.

Currently, non-vitamin K-antagonist oral anticoagulant (NOAC) monotherapy has been suggested as the optimal antithrombotic therapy for atrial fibrillation (AF) beyond one year after coronary revascularization. The aim of this study was to compare the outcomes between NOAC monotherapy and NOAC plus antiplatelet combination therapy using real-world data. Between 2015 and 2020, patients with AF who had received NOACs beyond one year after coronary revascularization were enrolled from Korean national insurance data. We emulated a pragmatic sequence of trials between the NOAC monotherapy and the antiplatelet combination therapy followed by propensity score matching. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCEs), a composite of all-cause death, myocardial infarction, and stroke. Among 206,407 person-trials from 4,465 individuals, we compared 3,275 pairs of the monotherapy and the matched combination therapy. During a median follow-up of 1.24 years, the incidence rate of MACCE was 19.4% and 20.0% per patient-year in the monotherapy group and the antiplatelet combination group, respectively (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.88-1.05; P = 0.422). Compared with the antiplatelet combination group, the monotherapy group had a significantly lower incidence rate of major bleeding, defined as intracranial bleeding or gastrointestinal bleeding requiring hospitalization (2.8% vs. 3.6% per patient-year; HR, 0.78; 95% CI, 0.62-0.97; P = 0.024). As an antithrombotic therapy for AF beyond one year after coronary revascularization, NOAC monotherapy was associated with a similar risk of MACCE and a lower risk of major bleeding compared to NOAC plus antiplatelet combination therapy.

Effectiveness of Early Direct Oral Anticoagulant Monotherapy within One Year of Coronary Stent Implantation in Patients with Atrial Fibrillation: A Nationwide Population-Based Study

We evaluated the effectiveness of early direct oral anticoagulant (DOAC) monotherapy within one year after percutaneous coronary intervention (PCI) in patients with atrial fibrillation (AF) using Korean National Health Insurance Service data. AF patients who underwent PCI were included and divided into the DOAC monotherapy group and the combination therapy group (DOAC with an antiplatelet agent) based on the medications used at 6 months after PCI. A major adverse cardiovascular event (MACE) was defined as a composite of cardiovascular death, acute myocardial infarction (AMI), stroke, or systemic thromboembolic event between 6 and 12 months after PCI. In the overall study population, the DOAC dose reduction rate was high in both the monotherapy group (70.8%) and the combination therapy group (79.1%). After propensity score matching, the MACE incidence was not significantly different between the two groups (hazard ratio [HR] 1.42 [0.90–2.24]). The numerical trend for higher MACE in the monotherapy group was mainly driven by the difference in stroke incidence (HR 1.84 [0.97–3.46]). All-cause death (HR 1.29 [0.61–2.74] or the incidence of major bleeding (HR 1.07 [0.49–2.35]) results were similar in the two groups. In conclusion, early DOAC monotherapy was not significantly associated with MACE risk between 6 and 12 months after PCI.

Effects of the factor Xa inhibitor rivaroxaban on the differentiation of endothelial progenitor cells

BackgroundWe evaluated the efficacy of the factor Xa inhibitor rivaroxaban on the differentiation ability of vascular endothelial progenitor cells (EPCs), which play roles in vascular injury repair and atherogenesis. Antithrombotic treatment in patients with atrial fibrillation undergoing percutaneous coronary intervention (PCI) is challenging, and current guidelines recommend oral anticoagulant monotherapy 1 year or more after PCI. However, biological evidence of the pharmacological effects of anticoagulants is insufficient.MethodsEPC colony-forming assays were performed using peripheral blood-derived CD34-positive cells from healthy volunteers. Adhesion and tube formation of cultured EPCs were assessed in human umbilical cord-derived CD34-positive cells. Endothelial cell surface markers were assessed using flow cytometry, and Akt and endothelial nitric oxide synthase (eNOS) phosphorylation were examined using western blot analysis of EPCs. Adhesion, tube formation and endothelial cell surface marker expression was observed in EPCs transfected with small interfering RNA (siRNA) against protease-activated receptor (PAR)-2. Finally, EPC behaviors were assessed in patients with atrial fibrillation undergoing PCI in whom warfarin was changed to rivaroxaban.ResultsRivaroxaban increased the number of large EPC colonies and increased the bioactivities of EPCs, including adhesion and tube formation. Rivaroxaban also increased vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, Tie-2, and E-selectin expression as well as Akt and eNOS phosphorylation. PAR-2 knockdown increased the bioactivities of EPCs and endothelial cell surface marker expression. Patients in whom the number of large colonies increased after switching to rivaroxaban showed better vascular repair.ConclusionsRivaroxaban increased the differentiation ability of EPCs, leading to potential advantages in the treatment of coronary artery disease.

Edoxaban Monotherapy in Nonvalvular Atrial Fibrillation Patients with Coronary Artery Disease.

Current guidelines recommend an oral anticoagulant (OAC) monotherapy in patients with nonvalvular atrial fibrillation (NVAF) and stable coronary artery disease (CAD) 1 year postpercutaneous coronary intervention (PCI). It might be possible to shorten the time for de-escalation from a dual therapy to monotherapy, but data regarding de-escalation to an edoxaban monotherapy are lacking. This study aimed to assess the clinical safety of an edoxaban monotherapy in patients with NVAF and stable CAD. A multicenter, prospective, randomized, open-label, and parallel group study was established to investigate the safety of an edoxaban monotherapy in patients with NVAF and stable CAD including over 6 months postimplantation of a third-generation DES and 1 year postimplantation of other stents (PRAEDO AF study). Between March 2018 and June 2020, 147 patients from 8 institutions in Japan were randomized to receive either an edoxaban monotherapy (n = 74) or combination therapy (edoxaban plus clopidogrel, n = 73). The primary study endpoint was the composite incidence of major bleeding and clinically significant bleeding, defined according to the ISTH criteria. Major or clinically significant bleeding occurred in 2 patients in the monotherapy group (1.67% per patient-year) and in 5 patients in the combination therapy group (4.28% per patient-year) (hazard ratio, 0.39; 95% confidence interval, 0.08-2.02). There was no incidence of a myocardial infarction, stent thrombosis, unstable angina requiring revascularization, ischemic stroke, systemic stroke, or hemorrhagic stroke in either of the groups. The edoxaban monotherapy was shown to have acceptable clinical safety in patients with NVAF and stable CAD. The study was registered with the Japan Registry of Clinical Trials (jRCTs031180119).

Bayesian Meta-analysis of Direct Oral Anticoagulation Versus Vitamin K Antagonists With or Without Concomitant Antiplatelet After Transcatheter Aortic Valve Implantation in Patients With Anticoagulation Indication.

Patients undergoing transcatheter aortic valve implantation (TAVI) commonly have co-morbidities requiring anticoagulation. However, the optimal post-procedural anticoagulation regimen is not well-established. This meta-analysis investigates safety and efficacy outcomes of direct oral anticoagulants (DOACs) and Vitamin K Antagonist (VKA), with or without concomitant antiplatelet therapy. We searched EMBASE and MEDLINE for appropriate studies. Subgroup analyses were performed for anticoagulant monotherapy and combined therapy with antiplatelet agents. Eleven studies (6359 patients) were included. Overall, there were no differences between DOACs and VKA for all-cause mortality (Odds Ratio [OR]: .69; Credible Interval [CrI]: .40-1.06), cardiovascular-related mortality (OR: .76; Crl: .13-3.47), bleeding (OR: .95; CrI: .75-1.17), stroke (OR: 1.04; CrI: .65-1.63), myocardial infarction (OR: 1.51; CrI: .55-3.84), and valve thrombosis (OR: .29; CrI: .01-3.54). For DOACs vs VKA monotherapy subgroup, there were no differences in outcomes. For the combined therapy subgroup, there was decreased odds of all-cause mortality in the DOACs group compared with the VKA group (OR: .13; CrI: .02-.65), but no differences for bleeding and stroke. DOACs and VKA have similar safety and efficacy profiles for post-TAVI patients with anticoagulation indication. However, if concomitant antiplatelet therapy is required, DOACs were more favorable than VKA for all-cause mortality.

Antithrombotic treatment beyond 1 year after percutaneous coronary intervention in patients with atrial fibrillation.

Beyond 1 year after percutaneous coronary intervention (PCI), guidelines recommend anticoagulant monotherapy in patients with atrial fibrillation (AF) rather than dual therapy with an anticoagulant and an antiplatelet drug. The risks and benefits of this strategy, however, remain uncertain. We examined hospitalization for bleeding and ischaemic risk beyond 1 year after PCI in patients with AF treated with monotherapy vs. dual therapy. Furthermore, among patients treated with monotherapy, we compared direct oral anticoagulant (DOAC) therapy and vitamin K antagonist (VKA) therapy. We included all patients with AF undergoing first-time PCI between 2003 and 2017 from the Western Denmark Heart Registry and followed them for up to 4 years. Follow-up started 15 months after PCI to enable assessment of medical treatment after 12 months. Using a Cox regression model, we computed weighted hazard ratios (HRw) of hospitalization for bleeding and major adverse cardiac events (MACEs). Analyses comparing monotherapy vs. dual therapy included 3331 patients, and analyses comparing DOAC vs. VKA monotherapy included 1275 patients. Risks of hospitalization for bleeding [HRw 0.90, 95% confidence interval (CI) 0.75-1.09] and MACE (HRw 1.04, 95% CI 0.90-1.19) were similar with monotherapy and dual therapy. Similarly, risks of hospitalization for bleeding (HRw 1.27, 95% CI 0.84-1.92) and MACE (HRw 1.15, 95% CI 0.87-1.50) were equal with DOAC and VKA monotherapy. Our results support long-term OAC monotherapy beyond 1 year after PCI in patients with atrial fibrillation and suggest that DOAC monotherapy is as safe and effective as VKA monotherapy.

Comparison of Efficacy and Safety of Anticoagulant Monotherapy and Combined Therapy of Anticoagulant and Antiplatelets in Patients With Stable Coronary Artery Disease and Atrial Fibrillation: A Meta-Analysis

It is still uncertain whether patients with atrial fibrillation (AF) andstable coronary artery disease (CAD) who require long-term oral anticoagulation (OAC) should also receive antiplatelet treatment (APT). This meta-analysis aims to compare the efficacy and safety of OAC alone with OAC plus APT in individuals with AF and stable CAD. The current meta-analysis was conducted as per the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the Meta-analysis of Observational Studies in Epidemiology (MOOSE).We performed electronic searches using PubMed, EMBASE, and Cochrane Library. The efficacy outcomes assessed in this meta-analysis included cardiovascular death, myocardial infarction, stroke (ischemic and hemorrhagic), and all-cause mortality. The safety outcome included major bleeding events. A total of five studies were included in the current meta-analysis enrolling 9199 patients with stable CAD and AF. Out of these five studies, three were observational and two were randomized controlled trials (RCTs). Our study showed no significant difference between two groups in the incidence of cardiovascular mortality (Hazard ratio {HR}: 0.86, 95% confidence interval {CI}: 0.59-1.25, I-square: 44%), myocardial infarction (HR: 1.21, 95% CI: 0.73-2.01, I-square: 0%), all-cause mortality (HR: 0.95, 95% CI: 0.76-1.19, I-square: 68%) and stroke (HR: 0.83, 95% CI: 0.61-1.12, I-square: 45%). However, lower incidence of major bleeding events in patients who received OAC alone as compared to patients who received a combination of OAC and anti-platelet (HR: 1.37, 95% CI: 1.18-1.580, I-square: 78%) were found. The current meta-analysis showed that OAC monotherapy is associated with a lower incidence of major bleeding events in patients with stable CAD and AF. It is also not associated with an increased risk of all-cause mortality, cardiovascular death, stroke, and myocardial infarction.

Dual therapy with oral anticoagulation and single antiplatelet agent versus monotherapy with oral anticoagulation alone in patients with atrial fibrillation and stable ischemic heart disease: a systematic review and meta-analysis.

In patients with atrial fibrillation (AF) and stable ischemic heart disease, recent guidelines recommend oral anticoagulant (OAC) monotherapy in preference to OAC + single antiplatelet agent (SAPT) dual therapy. However, these data are based on the results of only two randomized controlled trials (RCTs) and a relatively small group of patients. Thus, the safety and efficacy of this approach may be underpowered to detect a significant difference. We hypothesized that OAC monotherapy will have a reduced risk of bleeding, but similar all-cause mortality and ischemic outcomes as compared to dual therapy (OAC + SAPT). A systematic search of PubMed/MEDLINE, EMBASE, and Scopus was conducted. Safety outcomes included total bleeding, major bleeding, and others. Efficacy outcomes included all-cause mortality, cardiovascular mortality, myocardial infarction, stroke, and major adverse cardiovascular events (MACE). RCTs and observational studies were pooled separately (study design stratified meta-analysis). Subgroup analyses were performed for vitamin K antagonists and direct oral anticoagulants (DOACs). Pooled risk ratios (RR) with corresponding 95% confidence intervals (CI) were calculated using the Mantel-Haenszel method. Meta-analysis of 2 RCTs comprising a total of 2905 patients showed that dual therapy (OAC + SAPT) vs. OAC monotherapy was associated with a statistically significant increase in major bleeding (RR 1.51; 95% CI [1.10, 2.06]). There was no significant reduction in MACE (RR 1.10; [0.71, 1.72]), stroke (RR 1.29; [0.85, 1.95]), myocardial infarction (RR 0.57; [0.28, 1.16]), cardiovascular mortality (RR 1.22; [0.63, 2.35]), or all-cause mortality (RR 1.18 [0.52, 2.68]). Meta-analysis of 20 observational studies comprising 47,451 patients showed that dual therapy (OAC + SAPT) vs. OAC monotherapy was associated with a statistically significant higher total bleeding (RR 1.50; [1.20, 1.88]), major bleeding (RR = 1.49; [1.38, 1.61]), gastrointestinal bleeding (RR = 1.62; [1.15, 2.28]), and myocardial infarction (RR = 1.15; [1.05, 1.26]), without significantly lower MACE (RR 1.10; [0.97, 1.24]), stroke (RR 0.93; [0.73, 1.19]), cardiovascular mortality (RR 1.11; [0.95, 1.29]), or all-cause mortality (RR 0.93; [0.78, 1.11]). Subgroup analysis showed similar results for both vitamin K antagonists and DOACs, except a statistically significant higher intracranial bleeding with vitamin K antagonist + SAPT vs. vitamin K antagonist monotherapy (RR 1.89; [1.36-2.63]). In patients with AF and stable ischemic heart disease, OAC + SAPT as compared to OAC monotherapy is associated with a significant increase in bleeding events without a significant reduction in thrombotic events, cardiovascular mortality, and all-cause mortality.