BACKGROUND: Metabolism of oral anticoagulants (OAC) is affected by P-glycoprotein (P-gp)/ CYP3A4 enzyme. However, the P-gp/CYP3A4 inhibitors are unavoidably used with OACs.
METHODS: Medline, Cochrane, and Embase were systematically searched for randomized controlled trials and cohort studies from inception till 23rd November, 2022 to assess the safety and effectiveness of OACs when concomitantly used with P-gp/CYP3A4 inhibitors. The primary outcomes were major bleeding and gastrointestinal (GI) bleeding. Secondary outcomes were stroke/systemic embolism (SE), all-cause mortality, any bleeding as well as intracranial hemorrhage (ICH). We estimated summary odds ratios (OR) with 95% credible intervals (CI) using pairwise and network meta-analysis with random effects.
RESULTS: A total of 11 studies involving 37,973 patients were included. When concomitantly used with P-pg/ CYP3A4 inhibitors, network meta-analysis indicated that dabigatran, apixaban, and edoxaban were associated with significantly lower risk of major bleeding compared to rivaroxaban, with ORs of 0.56, 0.51 and 0.48, respectively. Rivaroxaban and dabigatran were associated with a significantly increased risk of GI bleeding than warfarin, apixaban and edoxaban. Dabigatran and apixaban were linked with significantly lower risk of any bleeding compared with warfarin (ORs were 0.75 and 0.68, respectively) or rivaroxaban (ORs were 0.67 and 0.60, respectively). Apixaban (OR 0.32) and edoxaban (OR 0.35) were associated with a lower risk of ICH compared with warfarin. There was no difference between any OACs in terms of stroke/SE or all-cause mortality.
CONCLUSIONS: When concomitantly used with P-gp/CYP3A4 inhibitors, apixaban and edoxaban were associated with a lower risk of bleeding, though no significant difference in effectiveness was observed among all OACs.

UNASSIGNED: Left ventricular thrombus (LVT) is a well-recognized complication of myocardial infarction (MI) in patients with diabetes. An embolic complication caused by LVT is a key clinical problem and is associated with worsened long-term survival.
UNASSIGNED: A 45-year-old man with persistent left abdominal pain for 1 week and left leg fatigue was admitted to the emergency department. The cause of abdominal pain was embolism of the renal artery, the splenic artery, and the superior mesenteric artery caused by cardiogenic thrombosis, which further led to splenic infarction and renal infarction. It was unclear when MI occurred because the patient had no typical critical chest pain, which may have been related to diabetic complications, such as diabetic peripheral neuropathy. Diabetes plays a pivotal role in MI and LVT formation. Because coronary angiography suggested triple vessel disease, percutaneous transluminal coronary angioplasty (PTCA) was conducted, and two drug-eluting stents were placed in the left anterior descending coronary artery (LAD). Due to a lack of randomized clinical control trials, the therapy of LVT and associated embolization has been actively debated. According to the present guidelines, this patient was treated with low-molecular-weight heparin and warfarin (oral anticoagulants) for 3 months in addition to aspirin (100 mg/day) and clopidogrel (75 mg/day) for 1 year. No serious bleeding complications were noted, and a follow-up examination showed no thrombus in the left ventricle or further peripheral thrombotic events.
UNASSIGNED: Peripheral embolization of LVT caused by MI leading to multiple organ embolization remains a rare occurrence. Diabetes plays a pivotal role in MI and LVT formation. Successful revascularization of the infarct-related coronary artery and anticoagulation therapy is important to minimize myocardial damage and prevent LVT. The present case will help clinicians recognize and manage LVT in patients with diabetes and related peripheral arterial thrombotic events with anticoagulation.

UNASSIGNED: The objective of this study was to evaluate the quality of anticoagulation by the time in therapeutic range (TTR) for patients with 12-week INR follow-up interval.
UNASSIGNED: From January 2018 to December 2020, a selective group of patients who underwent mechanical valve replacement and followed up at our anticoagulation clinic for adjustment of warfarin dose were enrolled. The incidences of complications of anticoagulation therapy were reported by linearized rates. TTR was calculated by the Rosendaal linear interpolation method.
UNASSIGNED: Two hundred and seventy-four patients were eligible for this study. The mean age of these patients was 52.8 ± 12.7 years, and 65.7% (180 cases) of them were females. The mean duration of warfarin therapy was 16.7 ± 28.1 months. A total of 1309 INR values were collected, representing 66789 patient days. In this study, the mean TTR was 63.7% ± 18.6%, weekly doses of warfarin were 20.6 ± 6.0 mg/weekly, and the mean monitoring interval for the patient was 53.6 ± 27.1 days. There were 153 cases in good TTR group (TTR ≥ 60%) and 121 cases in poor TTR group (TTR < 60%). The calculated mean TTR in both groups was 42.6% ± 22.1% and 74.8% ± 10.4%, respectively. Compared with the TTR ≥ 60% group, the TTR < 60% group exhibited a more prevalence of female gender (p = 0.001), atrial fibrillation (p < 0.001), NYHA ≥ III (p < 0.001), and lower preoperative left ventricular ejection fraction (LVEF, p = 0.032). In multivariate analysis, female gender (p = 0.023) and atrial fibrillation (p = 0.011) were associated with TTR < 60%. The incidence of major bleeding and thromboembolic events was 2.7% and 1.1% patient-years, respectively. There was one death which resulted from cerebral hemorrhage. The incidence of death was 0.5% patient-years. The difference in anticoagulation-related complications between the TTR < 60% group and the TTR ≥ 60% group was not statistically significant.
UNASSIGNED: For patients with stable international normalized ratio monitoring results who are follow-up at anticoagulation clinics, a 12-week monitoring interval has an acceptable quality of anticoagulation. The female gender and atrial fibrillation were associated with TTR < 60%.

UNASSIGNED: The efficacy and safety of antithrombotic treatment with oral anticoagulants (OACs) in elderly patients with comorbidities of acute coronary syndrome (ACS) and atrial fibrillation (AF) are unclear.
UNASSIGNED: A cohort of hospitalized elderly patients (≥65 years of age) diagnosed with ACS and AF and treated with oral antithrombotic agents were consecutively recruited. Follow-up was performed for at least 1 year. Major adverse cardiac events (MACEs) were defined as a composite of all-cause death, nonfatal myocardial infarction (MI), nonfatal stroke, and systemic embolism. The safety outcomes of bleeding were defined according to the Bleeding Academic Research Consortium (BARC) criteria.
UNASSIGNED: A cohort of 548 eligible patients (76 ± 6.6 years) was analyzed. Compared to the patients with OAC treatment (n = 184, 33.6%), patients treated without OAC (n = 364, 66.4%) were older, had a lower prevalence of persistent AF and unstable angina (UA), and more often presented with paroxysmal AF, acute myocardial infarction (AMI), stent implantation and dual antiplatelet therapy (DAPT). Compared to the patients without OAC treatment (n = 364, 66.4%), patients treated with OAC (n = 184, 33.6%) had a lower risk of MACEs at both the 1-year (4.3 vs. 15.1%, adjusted HR: 0.34, 95% CI: 0.15-0.80, p = 0.014) and 5-year (17.5 vs. 48.4%, adjusted HR: 0.36, 95% CI: 0.19-0.67, p = 0.001) follow-up. No significant difference was observed for bleeding events of BARC ≥2 between the groups (8.0 vs. 9.0%, adjusted HR: 1.17, 95% CI: 0.58-2.34, p = 0.667). Compared with warfarin-treated patients, the non-vitamin K antagonist oral anticoagulant-treated patients had lower risks of all-cause mortality (2.1 vs. 9.5%, HR: 0.18, 95% CI: 0.03-0.98, p = 0.047) and bleeding events of BARC ≥ 3 (2.1 vs. 4.8%, HR: 0.14, 95% CI: 0.02-1.10, p = 0.062).
UNASSIGNED: Antithrombotic therapy with OACs in elderly patients with ACS and AF was associated with a lower risk of ischemic events without an increase in bleeding events. In real-world practice, the clinical awareness of anticoagulation treatments in elderly patients with ACS and AF needs to be strengthened.

Background: Hypercoagulability and thromboembolic events are associated with poor prognosis in coronavirus disease 2019 (COVID-19) patients. Whether chronic oral anticoagulation (OAC) improve the prognosis is yet controversial. The present study aimed to investigate the association between the chronic OAC and clinical outcomes in COVID-19 patients. Methods: PubMed, Embase, Web of Science, and the Cochrane Library were comprehensively searched to identify studies that evaluated OAC for COVID-19 until 24 July 2021. Random-effects model meta-analyses were performed to pool the relative risk (RR) and 95% confidence interval (CI) of all-cause mortality and intensive care unit (ICU) admission as primary and secondary outcomes, respectively. According to the type of oral anticoagulants [direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs)], subgroup and interaction analyses were performed to compare DOACs and VKAs. Meta-regression was performed to explore the potential confounders on all-cause mortality. Results: A total of 12 studies involving 30,646 patients met the inclusion criteria. The results confirmed that chronic OAC did not reduce the risk of all-cause mortality (RR: 0.92; 95% CI 0.82-1.03; p = 0.165) or ICU admission (RR: 0.65; 95% CI 0.40-1.04; p = 0.073) in patients with COVID-19 compared to those without OAC. The chronic use of DOACs did not reduce the risk of all-cause mortality compared to VKAs (P interaction = 0.497) in subgroup and interaction analyses. The meta-regression failed to detect any potential confounding on all-cause mortality. Conclusion: COVID-19 patients with chronic OAC were not associated with a lower risk of all-cause mortality and ICU admission compared to those without OAC, and the results were consistent across DOACs and VKA subgroups. Systematic Review Registration: clinicaltrials.gov, identifier CRD42021269764.

OBJECTIVE: To investigate the efficacy and safety of the antithrombotic therapy using the oral anticoagulant rivaroxaban and clopidogrel in Chinese patients with acute coronary syndrome complicated with atrial fibrillation after percutaneous coronary intervention.
METHODS: A total of 100 patients were selected. Patients were randomly divided into two groups: the treatment group (rivaroxaban group) received a therapy of rivaroxaban and clopidogrel. The control group (warfarin group) receivied a combined treatment of warfarin, clopidogrel, and aspirin. The primary outcome endpoint was evaluated based on the adverse cardiac and cerebrovascular events within 12 months.
RESULTS: A total of 8 (8.00%) main adverse cardiac and cerebrovascular events occurred during the 12 months of follow-up, including 5 (9.80%) in the warfarin group and 3 (6.10%) in the rivaroxaban group. The risk of having main adverse cardiac and cerebrovascular events in the two groups was comparable (P = 0.479). A total of 9 patients (9.00%) were found to have bleeding events, among which 8 patients (15.7%) were in the warfarin group, whereas only 1 patient (2.00%) was in the rivaroxaban group. Therefore, the risk of bleeding in the warfarin group was significantly higher than that in the rivaroxaban group (P = 0.047).
CONCLUSIONS: In Chinese patients with acute coronary syndrome complicated with atrial fibrillation, the efficacy of the dual therapy of oral anticoagulant rivaroxaban plus clopidogrel after percutaneous coronary intervention was similar to that of the traditional triple therapy combined with warfarin, aspirin and clopidogrel, but it has a better safety property, which has potential to widely apply to antithrombotic therapy after PCI.

BACKGROUND: The aim of the study was to compare the real-world effectiveness and safety in atrial fibrillation (AF) patients treated with edoxaban versus other oral anticoagulants (OACs) (apixaban, dabigatran, rivaroxaban, and vitamin K antagonists [VKA]) in Germany.
RESULTS: Using a representative database of 3.5 million statutory health-insured lives in Germany, a retrospective cohort study was conducted to examine ischemic stroke (IS) or systemic embolism (SE) and major bleeding in AF patients initiating anticoagulant therapy from January 2014 through June 2017. Inverse probability of treatment weighting using propensity score was applied for baseline covariate adjustment. Cox proportional hazards models were used to estimate the adjusted risk (hazard ratio [HR]) of each outcome comparing edoxaban versus other OACs. Among 21,038 patients treated with OACs, 1236 edoxaban, 6053 apixaban, 1306 dabigatran, 7013 rivaroxaban, and 5430 VKA patients were included. The adjusted combined risks of IS or SE were lower (p < 0.05) for each edoxaban pairwise comparison with other OACs (HR: 0.83 vs. apixaban, 0.60 vs. dabigatran, 0.72 vs. rivaroxaban, 0.64 vs. VKA). Edoxaban favored lower risks of major bleeding compared with rivaroxaban (HR: 0.74) and VKA (HR: 0.47). No differences in the risk of major bleeding were found between edoxaban and apixaban (p = 0.33), and between edoxaban and dabigatran (p = 0.06).
CONCLUSIONS: Edoxaban was associated with better effectiveness compared with other OACs in AF patients from Germany. Edoxaban also demonstrated a favorable safety profile.

BACKGROUND: The optimal antithrombotic strategy, especially regarding oral anticoagulants (OACs) for atrial fibrillation (AF) patients with bleeding and thrombosis risk after percutaneous coronary intervention (PCI), remains unknown. This study explored the optimal oral anticoagulants for AF patients after PCI using a meta-analysis.
METHODS: Randomised controlled trials were identified from PubMed, Embase, and the Cochrane Library through December 2020. Risk ratios, 95% confidence intervals, and random-effects models were used to compare different antithrombotic strategies through network meta-analysis, and the combination of antithrombotic agents was ranked according to the surface under the cumulative ranking curve and rankograms. Interval plots were drawn to observe pairwise comparisons between the different strategies.
RESULTS: Five studies of 11,532 patients were included. Factor IIa inhibitor 110 mg bid plus a P2Y12 inhibitor had the greatest advantage for reducing Thrombolysis In Myocardial Infarction (TIMI) major or minor bleeding; Factor Xa inhibitor plus a P2Y12 inhibitor had the greatest advantage for reducing International Society on Thrombosis and Hemostasis major bleeding. For patients at risk of stroke plus all-cause death, factor IIa inhibitor 150 mg bid plus a P2Y12 inhibitor should be prioritised, and for those at risk of myocardial infarction and stent thrombosis, vitamin K antagonists plus a P2Y12 inhibitor were preferred.
CONCLUSIONS: Factor IIa inhibitor 110 mg, factor IIa inhibitor 150 mg, factor Xa inhibitor and vitamin K antagonists should be selected in different situations.

Prospective data on nonvitamin-K-antagonist oral anticoagulant (NOAC) management during cardiovascular interventions are limited. We therefore evaluated the safety and effectiveness of uninterrupted dabigatran therapy as well as dabigatran management during atrial fibrillation (AF)-cardioversions, AF-ablations, pacemaker implantations and coronary angiography and/or stenting procedures.
GLORIA-AF is an international registry programme involving patients with newly diagnosed AF. Dabigatran users were followed for ≤2 years. The primary outcome was occurrence of stroke/systemic embolism and major bleeding ≤8 weeks after a cardiovascular intervention during uninterrupted dabigatran therapy.
During the 2-year follow-up, 599 cardiovascular interventions were identified in 479 eligible patients. 412/599 (69%) interventions were performed with uninterrupted dabigatran therapy: 299/354 (84%) AF-cardioversions, 38/89 (43%) AF-ablations, 25/58 (43%) pacemaker implantations, and 50/98 (51%) coronary angiography and/or stenting procedures. During an average follow-up of 8.4 weeks after intervention, one major bleed and one systemic embolic event occurred (risk 0.25% for both outcomes; 95% confidence interval, 0.01%-1.36%).
More than two thirds of the interventions were performed with uninterrupted dabigatran therapy, of which most were AF-cardioversions. Uninterrupted dabigatran therapy was associated with low major bleeding and stroke/systemic embolism risk, supporting the favourable safety and effectiveness profile of dabigatran in clinical practice-based settings.

OBJECTIVE: This meta-analysis explored the safety and effectiveness of different anticoagulant regimens after left atrial appendage occlusion (LAAO).
METHODS: Databases, such as PubMed, MEDLINE, EMBASE, Web of Science, and Cochrane Library, were searched to identify eligible studies according to the inclusion criteria. The incidences of events, including device-related thrombus (DRT) formation, stroke, systemic thromboembolism, bleeding, cardiovascular mortality, and all-cause mortality, were analyzed using R version 3.2.3.
RESULTS: The screening retrieved 32 studies, including 36 study groups and 4,474 patients. The incidence of outcomes after LAAO was calculated via meta-analysis. In the subgroup analysis, the rates of DRT formation, cardiovascular mortality, and all-cause mortality were significantly different among different antithrombotic methods. Single antiplatelet therapy was associated with the highest rate of adverse events, followed by dual antiplatelet therapy (DAPT). Vitamin K antagonists (VKAs) and new oral anticoagulants (NOACs) carried lower rates of adverse events.
CONCLUSIONS: Anticoagulant therapy had better safety and efficacy than antiplatelet therapy. Thus, for patients with nonabsolute anticoagulant contraindications, anticoagulant therapy rather than DAPT should be actively selected. NOACs displayed potential for further development, and these treatments might represent alternatives to VKAs in the future.