Oral Anticoagulant Group Research Articles

Anticoagulation Use and Endovascular Thrombectomy in Patients with Large Core Stroke: A Secondary Analysis of the SELECT2 Trial.

Endovascular thrombectomy (EVT) safety and efficacy in patients with large core infarcts receiving oral anticoagulants (OAC) are unknown. In the SELECT2 trial (NCT03876457), 29 of 180 (16%; vitamin K antagonists 15, direct OACs 14) EVT, and 18 of 172 (10%; vitamin K antagonists 3, direct OACs 15) medical management (MM) patients reported OAC use at baseline. EVT was not associated with better clinical outcomes in the OAC group (EVT 6 [4-6] vs MM 5 [4-6], adjusted generalized odds ratio 0.89 [0.53-1.50]), but demonstrated significantly better outcomes in patients without OAC (EVT 4 [3-6] vs MM 5 [4-6], adjusted generalized odds ratio 1.87 [1.45-2.40], p = 0.02). The OAC group had higher comorbidities, including atrial fibrillation (70% vs 17%), congestive heart failure (28% vs 10%), and hypertension (87% vs 72%), suggesting increased frailty. However, the results were consistent after adjustment for these comorbidities, and was similar regardless of the type of OACs used. Whereas any hemorrhage rates were higher in the OAC group receiving EVT (86% in OAC vs 70% in no OAC), no parenchymal hemorrhage or symptomatic intracranial hemorrhage were observed with OAC use in both the EVT and MM arms. Although we did not find evidence that the effect was due to excess hemorrhage or confounded by underlying cardiac disease or older age, OAC use alone should not exclude patients from receiving EVT. Baseline comorbidities and ischemic injury extent should be considered while making individualized treatment decisions. ANN NEUROL 2024;96:887-894.

Atrial fibrillation and multimorbidity: How to choose the perfect direct oral anticoagulant?

Atrial fibrillation is one of the most common tachyarrhythmias, the prevalence of which is steadily increasing due to an increase in the proportion of the elderly population. The presence of a comorbidities in elderly patients with atrial fibrillation, increasing the risk of thromboembolic events, has a significant impact on the clinical strategy of atrial fibrillation, as well as on the choice of therapeutic tactics, especially anticoagulant therapy with proven efficacy and low risk of bleeding. One of the most common concomitant diseases in patients with atrial fibrillation are chronic kidney disease, anemia and coronary artery disease. These comorbidities in patients with atrial fibrillation not only increase the risk of stroke and/or systemic embolism, but are also accompanied by an increased risk of cardiovascular mortality, all causes mortality, and hemorrhagic events. At the same time, according to research data, about half of polymorbid patients with atrial fibrillation do not receive anticoagulant therapy, which indicates a low awareness of physicians about rational pharmacotherapy based on clinical recommendations for this cohort of patients. The drug of choice with the most studied safety profile and a high degree of efficacy in these patients is apixaban from the group of direct oral anticoagulants. Unlike vitamin K antagonists and other representatives of direct oral anticoagulants, apixaban, according to the conducted studies, is associated with a more significant reduction in the risk of thromboembolic events, and most importantly, has a lesser effect on the risks of bleeding in patients, predisposing to hemorrhagic complications, with atrial fibrillationand concomitant coronary artery disease, anemia, chronic kidney disease.

Stroke severity and outcomes in patients with intracerebral hemorrhage on anticoagulants and antiplatelet agents: an analysis from the Japan Stroke Data Bank.

Some patients with intracerebral hemorrhage are on antithrombotic agents at the time of the event and these may worsen outcome, but the relative risk of different oral anticoagulants and antiplatelet agents is uncertain. We determined associations between pre-onset intake of antithrombotic agents and initial stroke severity, and outcomes, in patients with intracerebral hemorrhage. Patients with intracerebral hemorrhage admitted within 24 hours after onset between January 2017 and December 2020 and recruited to the Japan Stroke Data Bank, a hospital-based multicenter prospective registry, were included. Enrolled patients were classified into four groups based on the type of antithrombotic agents being used on admission. The outcomes were the National Institutes of Health Stroke Scale (NIHSS) score on admission and modified Rankin Scale (mRS) of 5-6 at discharge. Of a total 9,810 patients with intracerebral hemorrhage (4,267 females; mean age, 70±15 years), 77.1% were classified into the no-antithrombotic group, 13.2% into the antiplatelet group, 4.0% into the warfarin group, and 5.8% into the direct oral anticoagulant (DOAC) group. Median (interquartile range) NIHSS score on admission was 12 (5-22), 13 (5-26), 15 (5-30), and 13 (6-24), respectively, in the four groups. In multivariable analysis, the pre stroke warfarin use was associated with higher NIHSS score (adjusted incidence rate ratio, 1.09 [95%confidence interval (CI), 1.06-1.13], with the no-antithrombotic group as the reference), but the antiplatelet group (1.00 [95%CI, 0.98-1.02]) and DOAC group (0.98 [95%CI, 0.95-1.01]) was not. The rate of mRS 5-6 at discharge was 30.8%, 41.9%, 48.6%, and 41.5%, respectively, in the four groups. In multivariable analysis, pre stroke warfarin use was associated with mRS 5-6 (adjusted odds ratio: 1.90 [95%CI, 1.28-2.81], with the no-antithrombotic group as the reference), but the antiplatelet group (1.12 [95%CI, 0.91-1.37]) and DOAC group (1.25 [95%CI, 0.88-1.77]) was not. Patients who were taking warfarin prior to intracerebral hemorrhage onset suffered more severe intracerebral hemorrhage as evidenced by higher admission NIHSS and higher discharge mRS. In contrast, no increase in severity was seen with antiplatelet agents.

Exploring bleeding in oral anticoagulant users: assessing incidence by indications and risk factors in the entire nationwide cohort.

Oral anticoagulants (OACs) are essential for the prevention and treatment of thromboembolic disorders, but bleeding, a major complication, can have a fatal impact on the patient's treatment. We aimed to estimate the nationwide, real-world incidence rate of bleeding in patients taking OACs and confirm the incidence by indications and risk factors. This cross-sectional study identified OAC users from April 1 to December 31, in both 2019 and 2020, using the HIRA-NPS database. The primary outcome variables were the incidence rate of major bleeding events during OAC treatment and within 30 days of treatment discontinuation. We estimated the adjusted incidence rate ratio (aIRR) in subpopulations. Among 18,822 OAC users, the incidence rate of major bleeding was 27.9 (95% CI: 24.6-31.5) per 1,000 person-years. The incidence rate of major bleeding was higher in patients with a bleeding history, with an aIRR of 11.51; those at high bleeding risk (HAS-BLED score ≥3), with an aIRR of 1.51; those with high CCI scores ≥3, with an aIRR of 1.88; and those with liver disease, with an aIRR of 1.41. For indications, compared to patients with nonvalvular atrial fibrillation (NVAF), the aIRR of major bleeding was significantly higher at an aIRR of 2.35 in patients undergoing VTE treatment. Patients with ischemic stroke showed a higher incidence of major bleeding with an aIRR of 2.13 than NVAF patients. The aIRR of major bleeding in the oral anticoagulant group, compared to the matched control group, was 2.25 (95% CI: 1.93-2.63). These findings may be useful for implementing strategies to improve the evaluation and management of anticoagulation-related bleeding.

Impact of anticoagulation therapy on outcomes in patients with cirrhosis and portal vein thrombosis: A large-scale retrospective cohort study

IntroductionPortal vein thrombosis in cirrhotic patients presents a significant clinical challenge. This study aims to (1) explore the impact of anticoagulation therapy on patient outcomes; (2) comparative outcomes in portal vein thrombosis treated between direct oral anticoagulant and Vitamin K Antagonist (VKA). Materials and methodsWe leveraged the TriNetX database to analyze a cohort comprising 4224 patients with liver cirrhosis and PVT who were treated with anticoagulation, alongside a comparison group of 15,300 patients with the same conditions but not receiving anticoagulation therapy. ResultsThe anticoagulated group showed a significant reduction in mortality (27.9 % vs. 34.2 %, HR = 0.723, 95 % CI: 0.678–0.770, P < 0.001). When comparing direct oral anticoagulant versus. VKA, in compensated liver cirrhosis, the direct oral anticoagulant group exhibited significantly lower mortality rates compared to VKA (17.7 % vs. 26.5 %, HR = 0.655, 95 % CI: 0.452–0.951, P = 0.025), with no significant difference in liver transplantation rates (4.0 % vs. 4.7 %, P = 0.080). In decompensated liver cirrhosis, the direct oral anticoagulant group exhibited lower mortality compared to the VKA group (23.6 % vs. 30.6 %, HR = 0.732, 95 % CI: 0.629–0.851, P < 0.001), and a higher frequency of liver transplantation was observed in the VKA group (10.6 % vs. 16.0 %, HR = 0.622, 95 % CI: 0.494–0.784, P < 0.001). Hospitalization rates were significantly lower in the direct oral anticoagulant group compared to the VKA group in decompensated cirrhosis (33.4 % vs. 38.3 %, HR = 0.830, 95 % CI: 0.695–0.992, P = 1.937). ConclusionsOur study offers compelling evidence supporting the use of anticoagulation therapy in liver cirrhosis with portal vein thrombosis. The use of DOACs in patients with both compensated and decompensated liver cirrhosis showed a marked mortality benefit.

Effect of direct oral anticoagulant therapy on pulmonary artery clot dissolution in intermediate high-risk pulmonary thromboembolism

BackgroundDirect oral anticoagulants are the established drugs for treating pulmonary thromboembolism. The advantage of direct oral anticoagulants over conventional therapy for clot lysis and right ventricular unloading in the acute phase remains unclear. This study aimed to evaluate the effect of acute treatment with direct oral anticoagulants on clot dissolution and right ventricular unloading in intermediate high-risk pulmonary thromboembolism.MethodsThirty patients with intermediate high-risk pulmonary thromboembolism admitted between November 2012 and December 2018 were included; 21 and 9 were treated with direct oral anticoagulants and conventional therapy, respectively. We compared the efficacy of clot dissolution and right ventricular unloading for intermediate high-risk pulmonary thromboembolism between direct oral anticoagulant and conventional therapy in the acute phase. Efficacy was assessed by computed tomography obstruction index, right/left ventricular ratio, and brain natriuretic peptide levels between baseline and at discharge.ResultsComputed tomography obstruction index, right ventricular/left ventricular ratio, and brain natriuretic peptide levels were significantly lower at discharge than at admission in both groups. The rate of improvement in computed tomography obstruction index was significantly higher in the direct oral anticoagulant therapy group than in the conventional therapy group (64 ± 15% vs. 47 ± 16%; p = 0.01). There were no significant differences in the rate of improvement in right ventricular/ left ventricular ratio and brain natriuretic peptide levels between the two groups.ConclusionsCompared with conventional therapy, direct oral anticoagulants significantly reduced pulmonary artery clot burden conventional therapy in the acute treatment of intermediate high-risk pulmonary thromboembolism.

Intraoperative haemoadsorption for antithrombotic drug removal during cardiac surgery: initial report of the international safe and timely antithrombotic removal (STAR) registry

Intraoperative antithrombotic drug removal by haemoadsorption is a novel strategy to reduce perioperative bleeding in patients on antithrombotic drugs undergoing cardiac surgery. The international STAR registry reports real-world clinical outcomes associated with this application. All patients underwent cardiac surgery before completing the recommended washout period. The haemoadsorption device was incorporated into the cardiopulmonary bypass (CPB) circuit. Patients on P2Y12 inhibitors comprised group 1, and patients on direct-acting oral anticoagulants (DOAC) group 2. Outcome measurements included bleeding events according to standardised definitions and 24-hour chest-tube-drainage (CTD). 165 patients were included from 8 institutions in Austria, Germany, Sweden, and the UK. Group 1 included 114 patients (62.9 ± 11.6years, 81% male) operated at a mean time of 33.2 h from the last P2Y12 inhibitor dose with a mean CPB duration of 117.1 ± 62.0 min. Group 2 included 51 patients (68.4 ± 9.4years, 53% male), operated at a mean time of 44.6 h after the last DOAC dose, with a CPB duration of 128.6 ± 48.4 min. In Group 1, 15 patients experienced a BARC-4 bleeding event (13%), including 3 reoperations (2.6%). The mean 24-hour CTD was 651 ± 407mL. In Group 2, 8 patients experienced a BARC-4 bleeding event (16%) including 4 reoperations (7.8%). The mean CTD was 675 ± 363mL. This initial report of the ongoing STAR registry shows that the intraoperative use of a haemoadsorption device is simple and safe, and may potentially mitigate the expected high bleeding risk of patients on antithrombotic drugs undergoing cardiac surgery before completion of the recommended washout period.Clinical registration number: ClinicalTrials.gov identifier: NCT05077124.Graphical

Comparing clinical outcomes of vitamin K antagonists vs non-vitamin K antagonists in anticoagulant therapy for mesenteric venous thrombosis

ObjectiveNon-vitamin K antagonist oral anticoagulants have shown similar efficacy and lower bleeding rates than vitamin K antagonists for venous thromboembolism. However, this has not been proven in mesenteric vein thrombosis. This study aimed to compare the clinical outcomes of vitamin K antagonists and non-vitamin K antagonist oral anticoagulants. MethodsBetween January 2014 and July 2022, mesenteric vein thrombosis was diagnosed on computed tomography in 225 patients in a tertiary hospital. Among them, a total of 44 patients who underwent long-term anticoagulation therapy over 3 months were enrolled in this study. Patients were divided into two groups based on the anticoagulant used: vitamin K antagonists (Group 1, n = 21) and non-vitamin K antagonist oral anticoagulants (Group 2, n = 23). The efficacy outcomes were symptom recurrence and thrombus resolution on follow-up computed tomography, and the safety outcome was bleeding complications. ResultsThe median age of the patients was 56 years (range, 46-68 years), and 52% were men. The most common risk factors were unprovoked intra-abdominal infections (30%). The median duration of anticoagulation therapy was 13 months (20 months in Group 1 vs 6 months in Group 2; P = .076). Of the 44 patients, 17 (39%) received the standard treatment. The median follow-up period was longer in Group 1 than in Group 2 (57 vs 28 months; P = .048). No recurrence of mesenteric vein thrombosis-related symptoms were observed in either group. The median duration of follow-up computed tomography was 31 months (42 months in Group 1 vs 18 months in Group 2; P = .064). Computed tomography revealed complete thrombus resolution, partial resolution, and no changes in 71%, 19%, and 10%, respectively (P = .075). Regarding bleeding complications, varix bleeding and melena developed in two patients in Group 2, and anticoagulation treatment thereafter ceased. ConclusionsDespite the short follow-up duration in the non-vitamin K antagonist oral anticoagulants group, there was no clinically significant difference in the thrombus resolution rate or bleeding complications when compared with the vitamin K antagonists group. Although research on the long-term effects of non-vitamin K antagonist oral anticoagulants in patients is limited, non-vitamin K antagonist oral anticoagulants can be considered an alternative to conventional treatments.

Prognostic impact of oral anticoagulation therapy and atrial fibrillation in patients with type B acute aortic dissection.

The prognostic impact of atrial fibrillation (AF) and oral anticoagulation (OAC) therapy in patients with type B acute aortic dissection (AAD) remains unclear. Therefore, we investigated the prognostic impact of AF and OAC therapy in patients with type B AAD. Consecutive patients diagnosed with AAD were included in this single-center, retrospective study. Patients with type B AAD were selected from the study population and divided into three groups: AF(+)/OAC(+), AF(+)/OAC(-), and AF(-)/OAC(-). The primary end point was major adverse cardiovascular and cerebrovascular events (MACCE), including all-cause death, progressive aortic events, cerebral infarction, and organ malperfusion. In total, 139 patients diagnosed with type B AAD were analyzed. AF was observed in 27 patients (19%). Among them, 13 patients (9%) received OAC therapy for AF. MACCE occurred in 32 patients (23%) during the observation period: all-cause death in four patients, progressive aortic events in 24 patients, cerebral infarction events in two patients, and malperfusion events in two patients. The incidence of MACCE was higher in the AF(+)/OAC(+) group than in the AF(+)/OAC(-) group (hazard ratio[HR]: 3.875; 95% confidence interval [CI]: 1.153-17.496). In contrast, there was no significant difference in the incidence of MACCE between the AF(+)/OAC(-) and AF(-)/OAC(-) groups (HR: 1.001, 95% CI: 0.509-1.802). Among patients with type B AAD, the use of OAC for AF was associated with a higher risk of MACCE.

All-Cause Death and Major Adverse Events in Atrial Fibrillation with Frailty: Observations from the Korea National Health Insurance Service Data.

Atrial fibrillation (AF) is an indicator of frailty in old patients. This study aimed to investigate the effect of frailty on the use of oral anticoagulants (OAC) and clinical outcomes in a nationwide cohort of patients with new-onset AF. This study included 451,368 participants without AF from the Korea National Health Insurance Service-Health Screening cohort between 2002 and 2009. The Hospital Frailty Risk Score was retrospectively calculated for each patient using all available International Classification of Disease 10th revision diagnostic codes. According to the aggregate score, patients were divided into two groups: the participants without frailty ( 5 points) and the participants with frailty ( 5 points). The primary outcome was death from any cause, and the secondary outcomes were cardiovascular death, ischemic stroke, major bleeding, and heart failure admission. With up to 7.2 1.5 years of follow-up, 11,953 participants (median age, 67 [interquartile range, 59.5-74.5] years; 7200 [60.2%] males) developed new-onset AF. Among the patients with AF, 3224 (26.9%) had frailty. Frailty was significantly associated with old age, female sex, polypharmacy, and other comorbidities. In patients with AF, frailty was negatively associated with OAC prescription after new-onset AF (p 0.001). Compared to patients without frailty, patients with frailty had a significantly higher incidence and risk of all-cause death (hazard ratio [HR] 2.88, 95% confidence interval [CI] 2.65-3.14), cardiovascular death (HR 2.42, 95% CI 2.10-2.80), ischemic stroke (HR 2.25, 95% CI 2.02-2.51), major bleeding (HR 2.44, 95% CI 2.17-2.73), and heart failure admission (HR 1.29, 95% CI 1.09-1.52). In subgroup analysis, when compared to the non-OAC group, the risks associated with frailty were significantly lower in the OAC group for all-cause death, cardiovascular death, ischemic stroke, and heart failure admission. Frailty was negatively associated with the use of OAC and was a predictor of poor prognosis owing to the association of frailty with death, thromboembolic events, bleeding, and heart failure admission. However, OAC use was associated with lower risks related to frailty for all-cause death and major adverse cardiovascular events in patients with AF.

Impact of Oral Anticoagulation on Clinical Outcomes in Postoperative Atrial Fibrillation

IntroductionThe impact of postoperative oral anticoagulation (OAC) with warfarin on postoperative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG) was the focus of this examination of patients from the randomized endo-vein graft prospective (REGROUP) Trial. Material and methodsREGROUP was a prospective randomized Veterans Affairs cooperative study comparing endoscopic versus open vein harvest in elective CABG patients (March 2014-April 2017) at 16 Veterans Affairs facilities. This study compared new-onset POAF patients who were treated with warfarin versus no-warfarin. Outcomes included stroke during active follow-up and a major adverse cardiac event composite of mortality, acute myocardial infarction, and repeat revascularization during active and passive follow-up. ResultsOf the 316/1103 (28.6%) of REGROUP patients who developed new-onset POAF, 45 patients were excluded - mainly for preoperative warfarin use. Of the remaining 269 patients, 85 received OAC with warfarin (OAC group); 184 did not (no-OAC group). Stroke rates during active follow-up (32 [IQR 24-38] mo) were 3.5% OAC group versus 5.4% no-OAC group (P = 0.76); major adverse cardiac eventrates were 20% OAC versus 11.4% no-OAC (P = 0.06). On longer follow-up of (median 4.61 [IQR 3.9-5.1] y), discharge OAC use was associated with all-cause mortality after adjusting for Society of Thoracic Surgeons mortality risk (20.0% versus 11.4% no-OAC use; HR = 2.00, 95% CI: 1.05-3.81, P = 0.035). ConclusionsREGROUP patients with POAF treated with OAC had similar stroke and higher mortality rates versus no-OAC patients. Further investigation of the risk-benefit ratio of OAC in post-CABG patients and which POAF patient subgroups might derive the most benefit with anticoagulation appears warranted.

Characteristics and Mechanism of Acute Ischemic Stroke in NAVF Patients With Prior Oral Anticoagulant Therapy.

We aimed to analyze the characteristics and mechanisms of acute ischemic stroke (AIS) in patients with nonvalvular atrial fibrillation (NVAF) who received prior anticoagulant therapy. We retrospectively analyzed the data of patients with NVAF and AIS between January 2016 and December 2021. Patients were divided into non-anticoagulant, adequate anticoagulant, and insufficient anticoagulant groups according to their prior anticoagulant status. Patients with prior anticoagulant therapy were further divided into warfarin and direct oral anticoagulant groups. A total of 749 patients (661 without anticoagulants, 33 with adequate anticoagulants, and 55 with insufficient anticoagulants) were included. Patients with adequate anticoagulant had a milder National Institute of Health Stroke Scale at presentation (P=0.001) and discharge (P=0.003), a higher proportion of Modified Rankin Scale (mRS) ≤2 at discharge (P=0.011), and lower rates of massive infarction (P=0.008) than patients without anticoagulant. Compared with the non-anticoagulant group, the proportion of intravenous thrombolysis was significantly lower in the adequate anticoagulant (P<0.001) and insufficient anticoagulant (P=0.009) groups. Patients in the adequate anticoagulant group had higher rates of responsible cerebral atherosclerotic stenosis (P=0.001 and 0.006, respectively) and competing large artery atherosclerotic mechanisms (P=0.006 and 0.009, respectively) than those in the other 2 groups. Compared with warfarin, direct oral anticoagulant was associated with higher rates of Modified Rankin Scale ≤2 at discharge (P=0.003). Adequate anticoagulant therapy may be associated with milder stroke severity and better outcomes at discharge in patients with NVAF. Competing large artery atherosclerotic mechanisms may be associated with anticoagulant failure in patients with NAVF with prior adequate anticoagulant therapy.

Outcomes of mechanical thrombectomy in orally anticoagulated patients with anterior circulation large vessel occlusion: a propensity-matched analysis of the Imperial College Thrombectomy Registry

BackgroundMechanical thrombectomy (MT) remains an effective treatment for patients with acute ischemic stroke receiving oral anticoagulation (OAC) and large vessel occlusion (LVO). However, to date, it remains unclear whether MT is safe in patients on treatment with OAC.AimsIn our study, we performed a propensity-matched analysis to investigate the safety and efficacy of MT in patients with acute ischemic stroke receiving anticoagulants. A propensity score method was used to target the causal inference of the observational study design.MethodsThis observational, prospective, single-centre study included consecutive patients with acute LVO ischemic stroke of the anterior circulation. Demographic, neuro-imaging and clinical data were collected and compared according to the anticoagulation status at baseline, patients on OAC vs those not on OAC. The primary study outcomes were the occurrence of any intracerebral haemorrhage (ICH) and symptomatic ICH. The secondary study outcomes were functional independence at 90 days after stroke (defined as modified Rankin Scale (mRS) scores of 0 through 2), mortality at 3 months and successful reperfusion rate according to the modified treatment in cerebral infarction (mTICI) score.ResultsOverall, our cohort included 573 patients with acute ischemic stroke and LVO treated with MT. After propensity score matching, 495 patients were matched (99 OAC group vs 396 no OAC group). There were no differences in terms of clinical characteristics between the two groups, except for the rate of intravenous thrombolysis less frequently given in the OAC group. There was no significant difference in terms of the rate of any ICH and symptomatic ICH between the two groups. With regards to the secondary study outcome, there was no significant difference in terms of the rate of successful recanalization post-procedure and functional independence at 3 months between the two groups. Patients in the OAC group showed a reduced mortality rate at 90 days compared to the patients with no previous use of anticoagulation (20.2% vs 21.2%, p = 0.031). Logistic regression analysis did not reveal a statistically significant influence of the anticoagulation status on the likelihood of any ICH (OR = 0.95, 95% CI = 0.46–1.97, p = 0.900) and symptomatic ICH (OR = 4.87, 95% CI = 0.64–37.1, p = 0.127). Our analysis showed also that pre-admission anticoagulant use was not associated with functional independence at 90 days after stroke (OR = 0.76, 95% CI = 0.39–1.48, p = 0.422) and rate of successful reperfusion (OR = 0.81, 95% CI = 0.38–1.72, p = 0.582).ConclusionAccording to our findings anticoagulation status at baseline did not raise any suggestion of safety and efficacy concerns when MT treatment is provided according to the standard guidelines. Confirmation of these results in larger controlled prospective cohorts is necessary.

NAT2 phenotype alters pharmacokinetics of rivaroxaban in healthy volunteers

Rivaroxaban is a direct inhibitor of factor Xa, a member of direct oral anticoagulant group of drugs (DOACs). Despite being a widely extended alternative to vitamin K antagonists (i.e., acenocoumarol, warfarin) the interindividual variability of DOACs is significant, and may be related to adverse drug reaction occurrence or drug inefficacy, namely hemorrhagic or thromboembolic events. Since there is not a consistent analytic practice to monitor the anticoagulant activity of DOACs, previously reported polymorphisms in genes coding for proteins responsible for the activation, transport, or metabolism of DOACs were studied. The study population comprised 60 healthy volunteers, who completed two randomized, crossover bioequivalence clinical trials between two different rivaroxaban formulations. The effect of food, sex, biogeographical origin and 55 variants (8 phenotypes and 47 single nucleotide polymorphisms) in drug metabolizing enzyme genes (such as CYP2D6, CYP2C9, NAT2) and transporters (namely, ABCB1, ABCG2) on rivaroxaban pharmacokinetics was tested. Individuals dosed under fasting conditions presented lower tmax (2.21 h vs 2.88 h, β = 1.19, R2 =0.342, p = 0.012) compared to fed volunteers. NAT2 slow acetylators presented higher AUC∞ corrected by dose/weight (AUC∞/DW; 8243.90 vs 7698.20 and 7161.25 h*ng*mg /ml*kg, β = 0.154, R2 =0.250, p = 0.044), higher Cmax/DW (1070.99 vs 834.81 and 803.36 ng*mg /ml*kg, β = 0.245, R2 =0.320, p = 0.002), and lower tmax (2.63 vs 3.19 and 4.15 h, β = −0.346, R2 =0.282, p = 0.047) than NAT2 rapid and intermediate acetylators. No other association was statistically significant. Thus, slow NAT2 appear to have altered rivaroxaban pharmacokinetics, increasing AUC∞ and Cmax. Nonetheless, further research should be conducted to verify NAT2 involvement on rivaroxaban pharmacokinetics and to determine its clinical significance.

Current use of oral anticoagulation therapy and influencing factors among coronary artery disease patients with nonvalvular atrial fibrillation in China

Objective: To investigate current use of oral anticoagulant (OAC) therapy and influencing factors among coronary artery disease (CAD) patients with nonvalvular atrial fibrillation (NVAF) in China. Methods: Results of this study derived from "China Atrial Fibrillation Registry Study", the study prospectively enrolled atrial fibrillation (AF) patients from 31 hospitals, and patients with valvular AF or treated with catheter ablation were excluded. Baseline data such as age, sex and type of atrial fibrillation were collected, and drug history, history of concomitant diseases, laboratory results and echocardiography results were recorded. CHA2DS2-VASc score and HAS-BLED score were calculated. The patients were followed up at the 3rd and 6th months after enrollment and every 6 months thereafter. Patients were divided according to whether they had coronary artery disease and whether they took OAC. Results: 11 067 NVAF patients fulfilling guideline criteria for OAC treatment were included in this study, including 1 837 patients with CAD. 95.4% of NVAF patients with CAD had CHA2DS2-VASc score≥2, and 59.7% of patients had HAS-BLED≥3, which was significantly higher than NVAF patients without CAD (P<0.001). Only 34.6% of NVAF patients with CAD were treated with OAC at enrollment. The proportion of HAS-BLED≥3 in the OAC group was significantly lower than in the no-OAC group (36.7% vs. 71.8%, P<0.001). After adjustment with multivariable logistic regression analysis, thromboembolism(OR=2.48,95%CI 1.50-4.10,P<0.001), left atrial diameter≥40 mm(OR=1.89,95%CI 1.23-2.91,P=0.004), stain use (OR=1.83,95%CI 1.01-3.03, P=0.020) and β blocker use (OR=1.74,95%CI 1.13-2.68,P=0.012)were influence factors of OAC treatment. However, the influence factors of no-OAC use were female(OR=0.54,95%CI 0.34-0.86,P=0.001), HAS-BLED≥3 (OR=0.33,95%CI 0.19-0.57,P<0.001), and antiplatelet drug(OR=0.04,95%CI 0.03-0.07,P<0.001). Conclusion: The rate of OAC treatment in NVAF patients with CAD is still low and needs to be further improved. The training and assessment of medical personnel should be strengthened to improve the utilization rate of OAC in these patients.

Predicting the Absolute Risk of Ischemic Stroke in Asian Patients with Atrial Fibrillation: Comparing the COOL-AF Risk Score with CARS/mCARS Models for Absolute Risk and the CHA2DS2-VASc Score

The aims of this study were (1) to validate the CARS and mCARS methods in an Asian population with atrial fibrillation (AF) and (2) to compare the CARS and mCARS models for absolute risk using the COOL-AF method and CHA2DS2VASc scores for the prediction of ischemic stroke or systemic embolism (SSE). We analyzed the results from a prospective nationwide multicenter AF registry. Follow-up data were collected for 3 years. The main outcomes were SSE. Predictive models of the 3-year SSE of the COOL-AF model, the CHA2DS2VASc score, the CARS for the no-OAC group, and the mCARS for the OAC group were developed and evaluated by C-statistics, and calibration plots were created for the whole group, as well as for oral anticoagulant (OAC) users and no-OAC patients. We studied 3405 patients (mean age: 67.8 years; 58.2% male, 75.4% OAC). The incidence rates of SSE were 1.51 (1.26-1.78), 1.93 (1.39-2.60), and 1.37 (1.10-1.68) for all patients, no-OAC patients, and OAC patients, respectively. For the whole population, the COOL-AF score had a C-statistic of 0.697 (0.682-0.713), which was superior to the CHA2DS2-VASc [0.655 (0.639-0.671)]. For the no-OAC group, the CARS predicted SSE with a C-statistic of 0.685 (0.652-0.716), which was similar to the CHA2DS2-VASc [0.684 (0.651-0.7150] and COOL-AF models [0.692 (0.659-0.723)]. For the OAC group, the mCARS had a C-statistic of 0.687 (0.669-0.705) that was similar to the COOL-AF [0.704 (0.686-0.721)] and better than the CHA2DS2-VASc score [0.655 (0.637-0.674)]. The calculation of the individual absolute risks using the CARS and mCARS models can predict SSE in an Asian population. Small differences were evident between the COOL-AF and CHA2DS2-VASc scores.

Optimal use of antithrombotic agents in ischemic stroke with atrial fibrillation and large artery atherosclerosis.

Optimal antithrombotic regimens to prevent recurrent stroke in patients with ischemic stroke due to atrial fibrillation (AF) and atherosclerotic large-vessel stenosis remain unknown. This study aimed to evaluate the effect of multiple antithrombotic therapies on outcomes at 1 year after ischemic stroke due to two or more causes. We identified 862 patients with ischemic stroke due to AF and large artery atherosclerosis from the linked data. These patients were categorized into three groups according to antithrombotic therapies at discharge: (1) antiplatelets, (2) oral anticoagulants (OAC), and (3) antiplatelets plus OAC. The study outcomes were recurrent ischemic stroke, composite outcomes for cardiovascular events, and major bleeding after 1 year. Inverse probability of treatment weighting (IPTW) was used to balance the three groups using propensity scores. Among 862 patients, 169 (19.6%) were treated with antiplatelets, 405 (47.0%) were treated with OAC, and 288 (33.4%) were treated with antiplatelets and OAC. After applying IPTW, only OAC had a significant beneficial effect on the 1-year composite outcome (hazard ratio (HR): 0.37, 95% confidence interval (CI): 0.23-0.60, p < 0.001) and death (HR: 0.35, 95% CI: (0.19-0.63), p < 0.001). The combination of antiplatelet agents and OAC group had an increased risk of major bleeding complications (HR: 5.27, 95% CI: (1.31-21.16), p = 0.019). However, there was no significant difference in 1-year recurrent stroke events among the three groups. This study demonstrated that OAC monotherapy was associated with lower risks of composite outcome and death in patients at 1 year after ischemic stroke due to AF and atherosclerotic stenosis. In addition, the combination of an antiplatelet and OAC had a high risk of major bleeding.

Antithrombotic therapy after TAVI: Better alone than with a bad company.

Key Points In transcatheter aortic valve implantation (TAVI) subset, previous randomized controlled trials reported increased mortality when anticoagulant therapy was used in subjects without a previous oral anticoagulation (OAC) indication. The current meta‐analysis confirms the worse clinical outcomes in anticoagulated patients as compared to subjects treated with antiplatelet, tough less subclinical valve thrombosis was found in the OAC group. At present, antiplatelet therapy (especially SAPT) seems the most reasonable approach in TAVI patients without indications for chronic OAC.

Oral Anticoagulation Therapy in Atrial Fibrillation Patients with Advanced Chronic Kidney Disease: CODE-AF Registry.

Advanced chronic kidney disease (CKD), including end-stage renal disease (ESRD) on dialysis, increases thromboembolic risk among patients with atrial fibrillation (AF). This study examined the comparative safety and efficacy of direct-acting oral anticoagulant (DOAC) compared to warfarin or no oral anticoagulant (OAC) in AF patients with advanced CKD or ESRD on dialysis. Using data from the COmparison study of Drugs for symptom control and complication prEvention of AF (CODE-AF) registry, 260 non-valvular AF patients with advanced CKD (defined as estimated glomerular filtration rate <30 mL/min per 1.73/m²) or ESRD on dialysis were enrolled from June 2016 to July 2020. The study population was categorized into DOAC, warfarin, and no OAC groups; and differences in major or clinically relevant non-major (CRNM) bleeding, stroke/systemic embolism (SE), myocardial infarction/critical limb ischemia (CLI), and death were assessed. During a median 24 months of follow-up, major or CRNM bleeding risk was significantly reduced in the DOAC group compared to the warfarin group [hazard ratio (HR) 0.11, 95% confidence interval (CI) 0.01 to 0.93, p=0.043]. In addition, the risk of composite adverse clinical outcomes (major or CRNM bleeding, stroke/SE, myocardial infarction/CLI, and death) was significantly reduced in the DOAC group compared to the no OAC group (HR 0.16, 95% CI 0.03 to 0.91, p=0.039). Among AF patients with advanced CKD or ESRD on dialysis, DOAC was associated with a lower risk of major or CRNM bleeding compared to warfarin and a lower risk of composite adverse clinical outcomes compared to no OAC. ClinicalTrials.gov (NCT02786095).

Assessing operative delay and complications in hip fracture patients on anticoagulants and antiplatelets

Hip fractures represent a prevalent geriatric cause of morbidity and mortality. The presence of multiple comorbidities requiring the use of an anticoagulant or antiplatelet medication adds complexity to management and influences outcomes. International guidelines suggest expedited surgery within 48 h; however, anticoagulant and antiplatelet medications commonly cause delays. Research exploring health outcomes in this group is unclear. Therefore, we aimed to determine the impact of anticoagulant and antiplatelet medications on operative delay and overall complications in hip fracture patients. A retrospective cohort study of hip fractures was performed at a tertiary hospital over a 3-year period from 1st January 2018 to 31st December 2020. Data collected included demographics, time to surgery, length of stay, postoperative blood transfusion, venous thromboembolism, acute coronary syndrome, stroke, infections in hospital and 120-day mortality. Patients were categorised based on the use of direct oral anticoagulants, warfarin and antiplatelet medications. In total, 474 patients were included and 43.5% were on an anticoagulant or antiplatelet medication. Patients on these medications had more than twice the rate of operative delay (41.7% versus 17.2%, p < 0.001) with the greatest in the direct oral anticoagulant group (92.7% delay). After controlling for age and gender, this was still significant for direct oral anticoagulant (p < 0.001) and antiplatelet group patients (p = 0.02). These patients also had a 20% increased overall complication rate (p < 0.001). On subgroup logistic regression, the increased complication rate was noted in the direct oral anticoagulant group (p = 0.006) and the antiplatelet group (p < 0.001) but not in the warfarin group (p = 0.25). Time to surgery beyond 48 h was associated with a double increase in the odds of a postoperative complication (p = 0.005). There is a significantly greater delay to surgery in hip fracture patients on anticoagulant or antiplatelet medications as well as a higher incidence of complications. Guidelines to expedite early safe surgery in this high-risk patient group are required.