Anticoagulant Monotherapy Research Articles

Antithrombotic therapy for patients with atrial fibrillation and stable coronary artery disease of 1-year and 3-year after percutaneous coronary intervention: a nationwide population-based study

Abstract Background In a recent trial, rivaroxaban monotherapy was noninferior for efficacy and superior for safety to rivaroxaban plus single antiplatelet therapy, as antithrombotic therapy for patients with atrial fibrillation (AF) and stable coronary artery disease (CAD). However, there are limited data regarding the comparative effectiveness and safety of oral anticoagulant (OAC) monotherapy versus OAC plus single antiplatelet therapy (SAPT) in real-world practice, especially after the introduction of direct oral anticoagulants (DOAC). Purpose To compare the effectiveness, safety, and net clinical benefit of OAC monotherapy to OAC plus SAPT in patients with AF and stable CAD of 1-year and 3-year after percutaneous coronary intervention (PCI) in a contemporary real-world observational cohort. Methods Using the Korean nationwide claims database, we included AF patients who underwent PCI from January 1, 2009 to February 28, 2019. Considering dynamic changes of antithrombotic therapy according to the period after receiving PCI, the index antithrombotic treatment was independently defined at the different time after receiving PCI and we conducted two cohort: 1-year and 3-year after PCI. In each cohort, the baseline characteristics of OAC monotherapy and OAC plus SAPT groups were balanced using inverse probability of treatment weighting (IPTW) methods. To assess clinical outcomes, ischemic stroke, myocardial infarction, major bleeding, and composite clinical outcomes of each outcome were analyzed. Results In cohort with 1-year after PCI, 678 patients with OAC monotherapy and 3159 patients with OAC plus SAPT were included. In cohort with 3-year after PCI, 1038 patients with OAC monotherapy and 2128 patients with OAC plus SAPT were enrolled. The baseline characteristics were well-balanced after IPTW between the two groups in both cohorts. Among total population, about 45% of patients prescribed DOAC as OAC treatment. Among patients with 1-year after PCI, OAC monotherapy and OAC plus SAPT showed comparable results for ischemic stroke, myocardial infarction, major bleeding, and composite clinical outcomes (Figure). In cohort with 3-year after PCI, OAC monotherapy and OAC plus SAPT showed comparable results for ischemic stroke and myocardial infarction, but OAC monotherapy was associated with a lower risk of the composite clinical outcome (hazard ratio [HR] 0.762, 95% confidence interval [CI] 0.607–0.950), mainly driven by reduction of major bleeding risk (HR 0.762, 95% CI 0.607–0.950) compared to OAC plus SAPT (Figure). Conclusion OAC monotherapy might be, at least, comparable choice for patients with AF and stable CAD compared to OAC plus SAPT. In patients with stable CAD more than 3-years after index PCI, OAC monotherapy could be better therapeutic choice to achieve less major bleeding and positive net clinical benefit. Funding Acknowledgement Type of funding sources: None.

Monotherapy for nonvalvular A-fib with stable CAD?

A meta-analysis found oral anticoagulant (OAC) monotherapy provided efficacy comparable to OAC plus single antiplatelet therapy-with lower bleeding risk.

Antithrombozytäre Therapie und Antikoagulation bei Patienten mit koronarer Herzerkrankung

Coronary heart disease (CHD) is a dynamic process with acute instable events and chronic periods leading to an increased mortality. Patients with CHD benefit from a differentiated antithrombotic therapy consisting of dual antiplatelet therapy in the acute phase and antiplatelet monotherapy or in combination with low dose anticoagulation (Xa-Inhibition) in the chronic phase. Current ESC-guidelines differentiate the acute coronary syndrome (ACS) and the chronic coronary syndrome (CCS). Depending on thrombotic burden, bleeding risk, comorbidities, such as atrial fibrillation, antiplatelet agents and oral anticoagulants in various combinations and dosages are used. In most scenarios in patients with ACS, the initial therapy will consist out of acetylsalicylic acid and a P2Y12-Inhibitor for 12 months followed by either a continuous monotherapy with acetylsalicylic acid (ASS), a prolonged dual antiplatelet therapy or a continuous dual antithrombotic therapy consisting of ASS and low dose rivaroxaban 2x daily. With atrial fibrillation as an underlying condition, an anticoagulant should be part of the therapy followed by anticoagulant monotherapy in the chronic phase of the disease (CCS). This article provides information about the different drugs and therapeutic algorithms based on the newest ESC-Guidelines and up to date studies.

Oral anticoagulant monotherapy vs oral anticoagulant/antiplatelet therapy for the management of atrial fibrillation and stable coronary artery disease

Abstract Funding Acknowledgements Type of funding sources: None. Background- The efficacy and safety of oral Anticoagulation (OAC)with either Warfarin or Direct oral anticoagulants (DOACs) as compared with combination therapy of oral anticoagulant and antiplatelet (OAC + APT) in patients with atrial fibrillation and stable coronary artery disease more than 1 year after stenting is not known. Methods-Electronic databases ( PubMed, Embase, Scopus) were searched from inception to December 28th, 2020. Unadjusted odds ratios (OR) were calculated from dichotomous data using Mantel Haenszel (M-H) random-effects with statistical significance to be considered if the confidence interval excludes 1 and p < 0.05. The primary efficacy end point was MACCE definied as composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, or death from any cause The primary safety end point was major bleeding, according to the criteria of the International Society on Thrombosis and Hemostasis; this end point was analyzed for superiority. Results- A total of seven studies with 81,303(OAC = 56,633; OAC + APT = 24670) participants were included. There was no statistically significant differences in MACCE among patients treated using OAC monotherapy compared with those treated with OAC + APT (HR 1.09; 95% CI 0.93-1.29; p = 0.28). OAC + APT was associated with a significantly higher risk of major bleeding compared with OAC monotherapy (HR 1.65; 95% CI 1.30-2.11; p < 0.0001) Conclusion- Amongst patients with atrial fibrillation and concomitant stable coronary artery disease, OAC monotherapy is non-inferior to combination therapy with OAC and single antiplatelet agent. OAC monotherapy reduced the risk for major or life-threatening bleeding events, while not increasing the risk for major adverse cardiovascular events. Abstract Figure.

SETAP: epidemiology and prevention of stroke and transient ischaemic attack in Czech patients with atrial fibrillation.

The aim of this study is to analyse the prevalence, epidemiology, and anticoagulation prevention of stroke or transient ischaemic attack (TIA) in Czech patients with atrial fibrillation (AF). Retrospective observational analysis of diagnoses, procedures, and treatment reported to the Czech National Registry of Reimbursed Healthcare Services between 2015 and 2018. Prevalence of AF in 2018 was 4.3% of Czech population and the prevalence of stroke/TIA in AF patients was 22.3% with annual incidence of 181.62 cases per 100 000 inhabitants. In 2018, CHA2DS2-ASc score ≥4 was present in 98% AF patients in secondary and 59% in primary prevention, respectively, while the anticoagulation treatment was used by 71-81% of them. Between 2015 and 2018, the percentage of AF patients treated with warfarin monotherapy in primary prevention decreased from 35% to 31%, with acetylsalicylic acid (ASA) monotherapy from 18% to 16% and non-vitamin K antagonist oral anticoagulants (NOACs) monotherapy increased from 7% to 11%. In secondary prevention, the percentage of warfarin monotherapy treatment decreased from 35% to 32%, with ASA monotherapy from 20% to 18% and with NOACs monotherapy increased from 9% to 15%. This study followed all Czech patients with AF. The unadjusted prevalence and incidence of AF was higher compared with other countries and 2019 European Society of Cardiology Statistics. The study identified several gaps in standard of reimbursed care. 20-30% of AF patients with other risk factors were without any prevention medication and the share of ASA monotherapy in treated patients was 16-18%.

Oral anticoagulant monotherapy compared to oral anticoagulant plus single anti-platelet therapy in stable ischemic heart disease with atrial fibrillation: a meta-analysis

Abstract Introduction Evidence for antithrombotic therapy regimen in patients with concurrent stable ischemic heart disease (SIHD) and atrial fibrillation (AF) is not well established. The ideal regimen needs to been balanced to prevent thrombotic and embolic events, without increasing the risk of bleeding tendencies. Two randomized control trials have been published studying oral anticoagulant monotherapy (OAC) as compared to oral anticoagulant plus single antiplatelet therapy (OAC+SAPT), of which one trial was terminated prematurely and was underpowered. Purpose We performed a meta-analysis of RCTs and observational studies comparing OAC monotherapy to OAC+ SAPT in SIDH patients with AF. Methods We performed a systematic search of the PubMed, EMBASE and Cochrane databases to identify relevant articles. The database search was performed from the inception of the databases to January 2020. Inclusion criteria were RCTs and observation studies comparing OAC to OAC+SAPT in SIDH patients with AF and reporting time to event outcomes of major bleeding or cardiovascular mortality. The definition of major bleeding as per the definition provided by individual studies. Two authors independently performed data extraction to check for reproducibility. We used inverse variance method with random effect model to calculate hazard ratio (HR) with 95% confidence interval (CI). Statistical heterogeneity was calculated using Higgins I2 statistics. All statistical analysis was performed using RevMan Version 5.3 (Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014). Results Seven studies (2 RCTs and 5 observational studies) were included in the final analysis. OAC+ SAPT as compared to OAC monotherapy in patients with SIHD and AF was associated with a higher incidence of major bleeding [HR: 1.59, 95% CI: 1.36–1.85, P value<0.05, I2: 0%] [Figure 1, Panel A]. OAC+SPT as compared to OAC monotherapy was associated with similar incidence of cardiovascular mortality [HR: 1.07, 95% CI: 0.86–1.33, P value= 0.55, I2: 32%] [Figure 1, Panel B]. There was no statistical heterogeneity associated with either pooled estimates. Conclusion OAC monotherapy as compared to OAC+SAPT in patients with SIHD and AF was associated with a lower incidence of major bleeding and similar incidence of cardiovascular mortality. Figure 1 Funding Acknowledgement Type of funding source: None

Comparison of Long-Term Outcomes Between Combination Antiplatelet and Anticoagulant Therapy and Anticoagulant Monotherapy in Patients With Atrial Fibrillation and Left Atrial Thrombi

Background: Anticoagulation for patients with atrial fibrillation (AF) complicated by left atrial thrombi (LAT) is a frequent cause of bleeding complications, but risk factors remain unknown.Methods and Results: Of 3,139 AF patients who underwent transesophageal echocardiography, 82 with LAT under anticoagulation were included in this study. Patients treated with combination antiplatelet and anticoagulant therapy (n=31) were compared with those receiving anticoagulant monotherapy (n=51) to investigate the effects of antiplatelet agents during anticoagulation on bleeding complications. Over a mean (±SD) follow-up of 878±486 days, bleeding events occurred more frequently in the combination therapy than monotherapy group (58% vs. 20%; P<0.001), but there was no significant difference in embolic events (6.5% vs. 3.9%; P=0.606). Kaplan-Meier analysis also showed a significantly higher rate of bleeding events in the combination therapy group, but no significant difference in the rate of embolic events. Inverse probability of treatment weighting revealed that combination therapy was independently associated with an increased risk of bleeding (hazard ratio [HR] 2.98, 95% confidence interval [CI] 1.14–7.89, P=0.026), but not with the risk of embolic events (HR 0.30, 95% CI 0.04–2.59, P=0.275). Net clinical benefit analysis was almost negative for combination therapy vs. monotherapy.Conclusions: In patients with AF and LAT, combination therapy was significantly associated with an increased risk of bleeding events, but not with a reduced risk of embolic events.

Safety and efficacy of anticoagulant monotherapy in atrial fibrillation and stable coronary artery disease: A systematic review and meta-analysis

BackgroundAdjunctive use of oral anticoagulant (OAC) and antiplatelet therapy (APT) in patients with stable coronary artery disease (CAD) and nonvalvular atrial fibrillation (AF) is a challenge of daily practice. MethodsA comprehensive literature search of databases was performed to identify studies comparing the safety and efficacy of OAC monotherapy and combined therapy (OAC plus single (S) APT). Events including major adverse cardiovascular events (MACE), all-cause mortality, stroke and major bleeding were analyzed. ResultsSeven articles comprising 11,070 subjects were identified. Combined therapy was associated with a significantly higher risk of major bleeding (pooled hazard ratio (HR) of 1.62, 95% CI 1.40–1.86, p=<0.0001) compared to the OAC monotherapy. There was no significant difference between the two comparison arms in terms of MACE (HR 1.14; 95% CI 0.97–1.34, p = 0.11), stroke (HR 1.05; 95% CI 0.77–1.43, p = 0.78) and all-cause mortality (HR 1.15; 95% CI 0.94–1.40, p = 0.16). Stratified analysis by inclusion of only patients with coronary stents attenuated the safety effect of monotherapy. Subgroup analysis based on the study design, type of OAC, major bleeding criteria and APT revealed findings consistent with the pooled HR. The combined therapy group had a 19% and 38% higher risk of MACE in studies with a history of MI (p = 0.03) and with the use of rivaroxaban (p = 0.02), respectively. ConclusionOAC monotherapy might have a lower incidence of major bleeding events with no higher overall risk of MACE, ischemic stroke and all-cause mortality compared to the combined therapy group.

Antithrombotic therapy in coronary artery disease patients with atrial fibrillation

BackgroundCoronary artery disease (CAD) and atrial fibrillation (AF) frequently coexist in clinical practice, making it challenging for the treating physician to choose anticoagulation and antiplatelet therapies. The aim of this study was to investigate antithrombotic strategies and assess related adverse outcomes in stable coronary artery disease (SCAD) and acute coronary syndrome (ACS) patients with AF when the CHA2DS2-VASc score was ≥2.MethodsWe performed a retrospective study and collected data from a computer-based patient record management system in Zhengzhou University People’s Hospital in China. In total, 2978 patients with a hospital discharge diagnosis of CAD and concomitant AF who met the inclusion criteria were enrolled from January 1, 2012 to December 31, 2016, and data from 2050 patients were finally analysed. The χ2 test was used to compare the incidences of clinical endpoints between the SCAD+AF group and the ACS + AF group. Multivariable Cox regression analysis was performed to identify independent predictive factors of adverse outcomes in both groups.ResultsOral anticoagulant (OAC) monotherapy was the most common antithrombotic therapy in SCAD+AF patients (49.55%), while double antiplatelet therapy (DAPT) was the most common treatment in ACS + AF patients (54.19%) at discharge. OAC monotherapy significantly increased and the use of single antiplatelet therapy (SAPT) decreased during follow-up (34 ± 13 months) when compared to their use at discharge in the SCAD+AF group (all p < 0.001). In the ACS + AF group, the proportion of patients using DAPT decreased notably, while the proportions of patients using SAPT and dual therapy (DT) combining OAC with SAPT increased significantly during follow-up (all p < 0.001) compared to the proportions at discharge. According to multivariable Cox regression analysis, age, hypertension and prior stroke were independent risk factors for ischaemic stroke in the SCAD+AF group and ACS + AF group (all p < 0.05). OAC was an independent protective factor for ischaemic stroke in both groups (all p < 0.05). Previous bleeding independently increased the risk of haemorrhage in both groups (all p < 0.01).ConclusionsIn this study, the proportion of anticoagulant-antiplatelet combined therapy was low in ACS + AF patients with high stroke risk. In clinical practice, the awareness of anticoagulation needs to be strengthened regarding patients with CAD and AF.

A Pilot Study of Monotherapy with a Non-Vitamin K-Antagonist Oral Anticoagulant following Watchman Left Atrial Appendage Closure in Patients with Non-Valvular Atrial Fibrillation

ABSTRACT Background The optimal medical therapy early after left atrial appendage closure (LAAC) is not well defined. A regimen that prevents thromboembolic events and device-related thrombus (DRT) while minimizing bleeding would be of clinical importance. Methods This was a single-center, prospective, open-label study. Patients undergoing commercially indicated WATCHMAN LAAC were treated with edoxaban monotherapy (i.e., without concomitant aspirin) for 6 weeks, at which time imaging and clinical follow-up were performed. A clinical events committee evaluated adverse events and at least 2 echocardiographers adjudicated follow-up imaging. The primary clinical endpoint was the composite of death, stroke, systemic embolism, or GUSTO-defined moderate or severe/life-threatening bleeding. The key imaging endpoint was DRT. Results A total of 75 patients were enrolled. The mean patient age was 79.6 ± 8.0 years, the mean CHA2DS2VASc score was 4.5 ± 1.3, the mean HAS-BLED score was 2.6 ± 0.8, and 46 patients (61.3%) had experienced a prior bleed. At a mean follow-up duration of 43 ± 8 days, the primary endpoint occurred in 1 patient (1.3%) as a result of a single GUSTO moderate bleed. DRT was observed in 1 patient (1.3%). Conclusions In this pilot study, monotherapy with edoxaban after WATCHMAN LAAC appeared safe and was associated with an acceptable rate of major bleeding and DRT. Whether a post-implant regimen of non-vitamin K oral anticoagulant monotherapy may be an alternative to the currently approved regimen of warfarin and aspirin, particularly in patients at high bleeding risk, should be further evaluated in a large, adequately powered trial.

Design and Rational for a Prospective Randomized Study of Safety Outcomes Treated with Edoxaban in Patients with Stable Coronary Artery Disease and Atrial Fibrillation (PRAEDO AF Study)

Background: In non-valvular atrial fibrillation (NVAF) patients with coronary artery disease (CAD), using antiplatelet drugs in addition to anticoagulants for stroke prevention may further increase the bleeding risk. Several guidelines have recommended an oral anticoagulant (OAC) monotherapy in patients with stable CAD one year after percutaneous coronary intervention (PCI). When considering early neointima healing of current 3rd generation drug-eluting stents (DESs), the duration of the de-escalation from a single antiplatelet drug plus an OAC to an OAC alone therapy can be shortened by less than one year after PCI. The data on the clinical acceptability of short durations for de-escalation to an edoxaban monotherapy in those patients are still lacking. Methods: A multicenter, prospective, randomized, open-label, parallel group study has been established to investigate the safety outcomes of an edoxaban monotherapy in NVAF patients with stable CAD for over at least 6 months after PCI (PRAEDO AF study). From 7 institutions in Japan, approximately 200 participants will be randomized to receive either edoxaban monotherapy or edoxaban plus clopidogrel. All patients will be followed-up at least 1 year after enrollment. The primary endpoint is the percentage of serious bleeding complications and clinically significant bleeding combined events according to the ISTH criteria for edoxaban alone and edoxaban plus an antiplatelet agent. Conclusions: This will be the first study to assess the safety of edoxaban monotherapy in NVAF patients with stable CAD over 6 months after the 3rd generation DES and over 12 months after 1st or 2nd DES implantations.

Vasculo-Behcet's Disease: Profile and Management - Single Center Experience

Background Behçet's disease (BD) is a multisystem vasculitis characterized by exacerbations and remissions with unknown etiology. Males are more affected than females with the usual onset in the third decade. Vascular involvement can occur in up to 40% of cases of BD. BD is unique among the vasculitides that it may involve all sizes and types of vessels. Objectives 1. To study the pattern of vascular involvement of Behçet's disease (BD) in the Saudi population; use of anticoagulation and its duration, thromboembolic, and major bleeding complications during anticoagulant therapy. 2. The effect of combined immunosuppression and anticoagulation treatment approach in reducing the risk of venous and arterial thromboembolism. 3. The role of vascular surgery for peripheral arterial and abdominal aortic aneurysms (AAA), and the role of immunosuppression in the treatment of pulmonary artery aneurysm (PAA) without the need for surgical intervention. Methods Twenty-three patients with confirmed vasculo-BD attending the thrombosis clinics at our tertiary care center between 2010 and 2015 were studied retrospectively and analyzed through descriptive statistics SPSS version 22. Results Demographics and pattern of vascular involvement are shown in tables 1 and 2. HLA-typing was performed for 13 patients, and HLA- B51 was positive in 7 (54%) patients tested. The acute phase reactants (ESR and CRP) were high in all 23 (100%). Hereditary and acquired thrombophilia workup was performed for all patients and only 1 (4.3%) was positive for antiphospholipid antibodies. Oral ulcers were present in all the patients, genital ulcers in 12 (52%), ocular involvement in 8 (35%), skin manifestations in 3 (13%), and arthritis in 1 (4.3%). Lower extremity vein thrombosis is the most frequent manifestation of Vasculo-BD in Saudi Arabia, followed by CVT, PAI, SVT/Budd-Chiari syndrome, IVC thrombosis, peripheral artery aneurysms, and AAA. Peripheral arterial and abdominal aortic aneurysms in 3 (13.6%), all of whom had successful vascular surgery for aneurysm repair. Inferior vena cava filter was inserted in 3 (13.6%). One patient was admitted to the intensive care unit with fulminant hepatic failure due to bilateral hepatic vein thrombosis and subsequently died. The vascular thrombosis recurrence was in 11 patients (48%, all venous) despite adherence to the prescribed anticoagulant therapy and lack of any provocation. These patients were initially treated with anticoagulant monotherapy. After combining immunosuppressive therapy to the pre-existing anticoagulant therapy, none had thrombosis recurrence. There was a complete resolution of the two patients with PAA with mono-immunosuppressant therapy and no surgical intervention. The most commonly prescribed initiation anticoagulant therapy was low molecular weight heparin (87%). Conclusion BD with vascular involvement continues to pose a major diagnostic and therapeutic challenge to physicians due to the heterogeneity of the clinical presentation and lack of the diagnostic laboratory test. Therefore, we must have a low threshold for BD in any patient with vascular thrombosis or aneurysm. Combined immunosuppressive therapy is essential in suppressing and preventing the venous and arterial recurrence attacks. Disclosures No relevant conflicts of interest to declare.

Hemorrhagic and thromboembolic complications in patients with implanted left ventricular assist devices in early postoperative period

The work is devoted to study hemorrhagic and thromboembolic complications in early postoperative period after implantation of left ventricular assist devices (LVAD). We performed retrospective analysis of 10 patients, males aged 55±13.5 years, with a BMI of 30.8±8.3, with a left ventricular ejection fraction ranging from 9% to 28%, which in the period from 11.03.2016 to 22.11.2017 year, in the Silesian center of the Heart Disease (Poland), in conditions of artificial blood circulation, LVAD was implanted. In the early postoperative period, patients received daily anticoagulant target therapy (ACCT), consisting of the following drugs: heparin (6-11 U/kg/h), aspirin (75-150 mg), Clopidogrel (75-150 mg), warfarin (1.5-7 mg), Nadroparinum Ca (0.3-0.6 ml/twice on day), Fondaparinux Na (2.5-5 mg/twice on day). Two patients received mono-heparin therapy, one patient received monotherapy with warfarin for 14 days. Other patients during the same period received combined heparin therapy in the first three days with a subsequent transition to warfarin, aspirin, Clopidogrel, Fraxiparin, or thrombin blocker. The mechanical support of the left ventricle was carried out essentially by two different implantable systems, performing one function of support of the left ventricle: POLVAD – programmed controlled pneumatic membrane mechanical circulation of blood to two patients, and LVAD program-controlled electro-centrifugal circulation for eight patients. The duration of support by POLVAD system was from 102 to 156 days. Length of support – LVAD ranged from 20 to 78 days. A comparison of the analyzed results led to the conclusion that anticoagulant mono-therapy with heparin or warfarin leads to an increase in the percentage of complications and mortality compared with the alternative combination anticoagulant targeted therapy consisting of the following drugs: heparin (6-11 U/kg/h), aspirin 75-150 mg), Clopidogrel (75-150 mg), warfarin (1.5-7 mg), Nadroparinum Ca (0.3-0.6 ml/ twice on day), Fondaparinux Na (2.5-5 mg/ twice on day), Where survival rates were significantly higher by 60%.

Clinical benefits and risks of antithrombotic therapy in patients with atrial fibrillation with comorbidities – A report from the CHART-2 Study

BackgroundThe benefits of antithrombotic therapy (ATT) for atrial fibrillation (AF) are occasionally offset by major bleeding complications. However, the clinical benefits and risks of ATT in AF patients, with special references to comorbidities, such as heart failure (HF), coronary artery disease (CAD), and the patterns of AF, remain to be fully elucidated. MethodsA total of 3221 consecutive AF patients from our Chronic Heart Failure Analysis and Registry in the Tohoku District-2 (CHART-2) Study (N = 10,219) were divided into 4 groups based on ATT at enrollment; no-ATT, anticoagulant alone, antiplatelet alone, and both of them (AC&AP). Then, efficacy and safety outcomes including thromboembolic events, major bleeding, and mortality were evaluated among the 4 groups. ResultsAnticoagulant monotherapy was associated with reduced risk of ischemic stroke in patients with but not in those without HF, CAD, or non-paroxysmal AF. Although there was no significant difference in major bleeding among the 4 groups, a composite of thromboembolism and major bleeding occurred more frequently in the AC&AP group, even in combination with anticoagulants and single antiplatelet therapy, indicating that the combination therapy is more harmful than anticoagulant monotherapy for AF patients, especially for those with HF or CAD. Lastly, no-ATT group was associated with worse prognosis compared with other 3 groups. ConclusionsThese results indicate that ATT is beneficial for AF patients particularly for those with HF, CAD, or non-paroxysmal AF and that among ATT, anticoagulant monotherapy may be most profitable for both clinical benefits and risks for AF patients.

Antithrombotic therapy in patients with atrial fibrillation undergoing coronary artery stenting.

Updates to the primary literature and clinical practice guidelines on use of antithrombotic combinations for patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) and stenting are reviewed. Up to 8% of patients undergoing PCI have AF and thus require both antiplatelet and anticoagulation therapies, which put them at increased risk for bleeding. Current literature suggests that using a single antiplatelet agent in combination with oral anticoagulation with a direct-acting oral anticoagulant (i.e., dual therapy) is effective and associated with less bleeding risk than triple therapy (dual antiplatelet therapy plus an oral anticoagulant) in patients with AF undergoing PCI with stent placement. The most recently studied dual therapy regimens consist of clopidogrel in combination with apixaban, rivaroxaban, or dabigatran. Guidelines recommend use of an oral anticoagulant plus clopidogrel and aspirin for a short period of time. In general, aspirin should be discontinued in most patients at discharge. In patients with a high risk of thrombosis, aspirin can be continued for up to 1 month. Dual therapy should be continued for 12 months, with oral anticoagulant monotherapy continued thereafter. A review of current literature on antithrombotic therapy in patients with AF undergoing PCI and subsequent coronary artery stenting indicates that the favored regimen is dual therapy consisting of clopidogrel with rivaroxaban, apixaban, dabigatran, or a vitamin K antagonist. Aspirin may be used in the periprocedural period but should be discontinued thereafter to reduce the risk of bleeding. Decisions regarding specific agents and duration of treatment should be based on thrombotic risk, bleeding risk, and patient preference.

Meta-Analysis of Oral Anticoagulant Monotherapy as an Antithrombotic Strategy in Patients With Stable Coronary Artery Disease and Nonvalvular Atrial Fibrillation

Guidelines recommend oral anticoagulant (OAC) monotherapy without antiplatelet therapy (APT) in patients with nonvalvular atrial fibrillation (AF) with stable coronary artery disease (CAD) of >1 year after myocardial infarction or percutaneous coronary intervention. More evidences are required for the safety and efficacy of OAC monotherapy compared with OAC plus APT. PubMed, EMBASE, and Cochrane Database of Systematic Reviews were systematically searched up to February 2019. Nonrandomized studies and randomized clinical trials comparing OAC monotherapy with OAC plus single APT (SAPT) for patients with stable CAD and nonvalvular AF. The primary end point was major adverse cardiovascular events (composite of ischemic or thrombotic events) and secondary outcomes included major bleeding, stroke, all-cause death, and net adverse events (composite of ischemic, thrombotic, or bleeding events). From 6 trials, 8,855 patients were included. There was no significant difference in major adverse cardiovascular event in patients with AF treated using OAC plus SAPT compared with those treated with OAC monotherapy (hazard ratio [HR] 1.09; 95% confidence interval [CI] 0.92 to 1.29). OAC plus SAPT was associated with a significantly higher risk of major bleeding compared with OAC monotherapy (HR 1.61; 95% CI 1.38 to 1.87), as well as in terms of net adverse event (HR 1.21; 95% CI 1.02 to 1.43). There were no significant differences in rates of stroke and all-cause death. In conclusion, in this meta-analysis, OAC monotherapy and OAC plus SAPT treatment showed similar effectiveness, but OAC monotherapy was significantly associated with a lower risk of bleeding compared with OAC plus SAPT in patients with nonvalvular AF and stable CAD.

Outcomes of anticoagulated patients with atrial fibrillation treated with or without antiplatelet therapy - A pooled analysis from the PREFER in AF and PREFER in AF PROLONGATON registries

BackgroundEvidence on whether antiPLT added to OACs is of advantage in atrial fibrillation (AF) patients with concomitant stable coronary artery disease (CAD) is limited. We evaluated clinical outcomes with oral anticoagulant (OAC) monotherapy vs antiplatelet therapy (antiPLT) plus OAC in patients with AF and stable CAD. MethodsData on 1058 AF patients on OACs and history (>1 year) of myocardial infarction or coronary stenting were pooled from the PREFER-in-AF and PREFER-in-AF PROLONGATION registries. We primarily compared the 1-year incidence of a net composite endpoint (primary endpoint), including acute coronary syndrome and major bleeding, with or without antiPLT. ResultsThe incidence of the primary net composite endpoint was significantly higher in patients receiving OACs + antiPLT (N = 348) vs OACs alone (N = 710): 7.9 vs 4.2 per 100 patients/year; adjusted OR [95% CI] 1.84 [1.01–3.37]; p = 0.048. Among the components of the primary endpoint, the greatest relative difference was found for major bleeding (OR [95% CI] 2.28 [95% CI 1.00–5.19]), and especially life-threatening or non-gastrointestinal bleeding. The net clinical outcome with OACs + antiPLT was poorer irrespective of the type of CAD (previous infarction or coronary stenting), the type of stent (bare metal or drug-eluting) or the type of OAC (vitamin K antagonist or non-vitamin K antagonist OAC). ConclusionsAmong patients with AF and stable CAD >1-year after the index event, the addition of antiPLT to OAC does not apparently provide added protection against coronary events, but increases major bleeding. OAC monotherapy should thus be considered the antithrombotic therapy of choice for such patients.

NOAC monotherapy in patients with concomitant indications for oral anticoagulation undergoing transcatheter aortic valve implantation.

Antithrombotic therapy after transcatheter aortic valve implantation (TAVI) is highly controversial and guideline recommendations are not evidence based. We assessed efficacy and safety of non-vitamin K antagonist oral anticoagulant (NOAC) monotherapy in patients with concomitant indications for OAC undergoing TAVI. Among more than 1300 TAVI patients since 2008, 154 patients were identified who received postinterventional NOAC monotherapy. Outcomes were compared to 172 patients treated with vitamin K antagonist (VKA) monotherapy. Thromboembolic as well as bleeding complications were analysed for 6 months after TAVI. Despite high CHA2DS2-Vasc (4.6 ± 1.2), HEMORR2HAGES (4.7 ± 1.9) and HASBLED (2.7 ± 0.8) scores only three major/life-threatening bleedings and four thromboembolic events occurred after NOAC therapy had been initiated post-TAVI. 12 patients (7.8%) died within 6 months after the procedure. Compared to patients being treated with VKA monotherapy, analysis of a combined end-point of post-procedural death, stroke, embolism and severe bleeding revealed no significant differences (17/154 vs. 14/172; p = 0.45). The results of this study suggest that NOAC therapy without additional antiplatelet treatment is effective and safe in patients with concomitant indications for OAC undergoing TAVI.

Taking Warfarin with Heparin Replacement and Direct Oral Anticoagulant Is a Risk Factor for Bleeding after Endoscopic Submucosal Dissection for Early Gastric Cancer

Background: Although bleeding after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) remains problematic, especially in patients taking anticoagulants, there are differing views on the ideal and optimal management for these patients. This study investigated the risk of bleeding after ESD in patients taking anticoagulants. Methods: We enrolled 61 consecutive patients taking anticoagulants (anticoagulant group) and 968 patients taking no antithrombotic agents (non-antithrombotic group) treated with ESD for EGC between December 2010 and October 2016. We analyzed the risk factors for bleeding after ESD in relation to the various clinical factors. Results: Incidences of bleeding after ESD were significantly higher (14%; 11/76) in the anticoagulant group compared to the non-antithrombotic group (3%; 40/1,167). Moreover, bleeding after ESD was significantly more common in patients in the warfarin monotherapy group (14%; 5/37) and in the direct oral anticoagulant (DOAC) monotherapy group (22%; 4/18), compared to the non-antithrombotic group. Multivariate analysis revealed that dialysis, the use of anticoagulants, and an operation time ≥75 min were independent risk factors for bleeding after ESD. Conclusions: Our data suggest that patients who take warfarin and receive heparin bridging, and those who take DOAC medication, are prone to bleeding after ESD for EGC.

Characteristics of patients with atrial fibrillation prescribed antiplatelet monotherapy compared with those on anticoagulants: insights from the GARFIELD-AF registry.

Current atrial fibrillation (AF) guidelines discourage antiplatelet (AP) monotherapy as alternative to anticoagulants (ACs). Why AP only is still used is largely unknown. Factors associated with AP monotherapy prescription were analysed in GARFIELD-AF, a registry of patients with newly diagnosed (≤6 weeks) AF and ≥1 investigator-determined stroke risk factor. We analysed 51270 patients from 35 countries enrolled into five sequential cohorts between 2010 and 2016. Overall, 20.7% of patients received AP monotherapy, 52.1% AC monotherapy, and 14.1% AP + AC. Most AP monotherapy (82.5%) and AC monotherapy (86.8%) patients were CHA2DS2-VASc ≥2. Compared with patients on AC monotherapy, AP monotherapy patients were frequently Chinese (vs. Caucasian, odds ratio 2.73) and more likely to have persistent AF (1.32), history of coronary artery disease (2.41) or other vascular disease (1.67), bleeding (2.11), or dementia (1.81). The odds for AP monotherapy increased with 5 years of age increments for patients ≥75 years (1.24) but decreased with age increments for patients 55-75 years (0.86). Antiplatelet monotherapy patients were less likely to have paroxysmal (0.67) or permanent AF (0.57), history of embolism (0.56), or alcohol use (0.90). With each cohort, AP monotherapy declined (P<0.0001), especially non-indicated use. AP + AC and no antithrombotic therapy were unchanged. However, even in 2015 and 2016, about 50% of AP-treated patients had no indication except AF (71% were CHA2DS2-VASc ≥2). Prescribing AP monotherapy in newly diagnosed AF has declined, but even nowadays a substantial proportion of AP-treated patients with AF have no indication for AP. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362.