Non-anticoagulated Patients Research Articles

Anticoagulation, photoselective vaporization of the prostate and safety : a propensity score-matched study.

We compared surgical complications after laser prostatic photovaporization in anticoagulated versus non-anticoagulated patients. A propensity score was calculated and patients were matched, to compare postoperative complications using the Clavien-Dindo classification between the anticoagulated and non-anticoagulated groups. We also identified factors associated with complications, and perform an analysis of secondary endpoint with categories of urological complications. We included all patients that benefited a photovaporization between 2013 and 2022, either 811 patients, reducing to 245 after propensity score matching for anticoagulation. After propensity score matching, there were no differences in baseline characteristics between groups. Ninety five patients (38%) were receiving anticoagulants; 162 (66%) had an ASA score ≥ 3. Among 86 patients (35%) who experienced complications within 3 months postoperatively, 92% had a Clavien Dindo score ≤ 2. By multivariate analysis, anticoagulation was not statistically significant, the only significant risk factor for complications was ASA score ≥ 3 (Odds ratio (OR) 2.2; 95% confidence interval (CI) [1.2-4.1]). Secondary endpoint analysis for hematuria found ASA score of 3 or higher and anticoagulant treatment statistically significant in univariate and multivariate analysis, with OR of 2.9 (95% CI [1.1-7.4]) and OR of 3.5 (95% CI [1.7-7.5]), respectively. Green light laser photovaporization of the prostate demonstrates significant safety, even in frail patients on anticoagulant therapy.

Refining the CHA2DS2VASc risk stratification scheme: Shall we drop the Sex Category criterion?

The CHA2DS2VASc score is recommended for stroke risk stratification in patients with atrial fibrillation (AF). This score assigns one extra point to female sex based on evidence from the early 2000s suggesting higher thromboembolic risk in women. This incremental risk of thromboembolism in women has decreased over time between 2007 and 2018, becoming non-significant in recent years. To assess the impact of removing the sex category (Sc) from the CHA2DS2VASc score, thus validating a non-sex CHA2DS2VASc (i.e., CHA2DS2VA) score. We analysed UK primary and secondary care data comprising 195,719 patients with AF followed between 1998-2016 (mean age: 75.9±12.3 years; 49.2% women). Among 126,428 non-anticoagulated patients, we compared the CHA2DS2VASc vs. CHA2DS2VA scores every calendar year. Throughout 413,007 patient-years, a total of 8,742 events of ischaemic stroke or systemic embolism were recorded. Sex differences in thromboembolic risk were not observed in the lower-risk population, but higher stroke rates were consistently seen in female patients in the higher-risk category (i.e., CHA2DS2VA ≥2). C-statistics for both CHA2DS2VA and CHA2DS2VASc scores were similar over the years (ranging from 0.62 to 0.71). With CHA2DS2VA no relevant differences were observed in IDI, and NRI resulted in improved reclassification (11%) in lower thromboembolic risk groups. NRI suggested misclassification in higher thromboembolic risk patients (-7%), but this did not affect their indication for anticoagulation (i.e., patients retained their high-risk status). Removing Sc from the CHA2DS2VASc score does not affect its ability to discriminate thromboembolic events in the AF population. Use of CHA2DS2VA may simplify initial decision-making for thromboprophylaxis.

The effect of early surgery on clinical outcomes in proximal femoral fracture patients receiving chronic anticoagulation: A japanese nationwide database study

Introduction: Surgery is often delayed in patients with proximal femoral fractures who receive oral anticoagulants, to avoid complications related to perioperative bleeding. However, surgery delay may increase the risk of postoperative mortality. Our primary goal was to understand whether anticoagulated patients benefit from early surgery in terms of survival and perioperative complications.Methods: This is a multicenter retrospective cohort study of 581,189 patients with proximal femoral fractures. About 2.0 % (n = 11,385) received direct oral anticoagulants (DOAC) and 1.5 % (n = 8,726) received warfarin. Surgery was performed within 48 h in 37.6 % of DOAC patients, 27.6 % of warfarin patients and in 41.9 % of nonanticoagulated patients. Survival analysis was applied to compare mortality rate, blood transfusions, systemic complications and surgical complications during hospitalization between the study groups.Results: Patients receiving anticoagulation were older and had more comorbidities than patients without anticoagulation. There were overall similar rates of mortality (0.8 %, 1.1 % and 1.2 %) and surgical complications (2.1 %, 2.1 % and 2.2 %) in non-anticoagulated, DOAC and warfarin patients. Blood transfusions and systemic complications were higher in all anticoagulated patients regardless of surgery timing. There were comparable rates of early surgery (41.9 %, 37.6 % and 27.6 %, respectively). When operated early, DOAC patients had more surgical complications (OR=1.24, p = 0.04). Warfarin patients operated early had higher mortality (OR=1.48, p = 0.08) and higher risk of blood transfusions (OR=1.24, p < 0.001).Discussion: Age and comorbidities could explain higher rates of postoperative systemic complications in anticoagulated patients. Nevertheless, overall short-term mortality was similar between the groups. Early surgery was associated with higher rates of surgical complications in DOAC patients. When operated early, patients receiving warfarin were at an increased risk of mortality (p = 0.08) and perioperative blood transfusions.

Association between antithrombotic drug regimen changes and clinical outcomes after stroke in atrial fibrillation

BackgroundThe impact of post-stroke antithrombotic regimen in atrial fibrillation is uncertain. ObjectiveThis study aimed to describe antithrombotic therapy prescribing patterns after ischemic stroke and the impact on outcomes. MethodsA total of 23,165 patients with atrial fibrillation experiencing ischemic stroke were identified. Subsequent post-stroke events included recurrent ischemic stroke, intracranial hemorrhage, major bleeding, mortality, and composite outcomes. ResultsOf those who were nonanticoagulated before a stroke, 33.5% remained nonanticoagulated and 39.2% were prescribed only antiplatelet agents (APs) after a stroke. Compared with non–vitamin K antagonist oral anticoagulants (NOACs) after stroke, there was a significant increase in ischemic stroke and mortality in nonanticoagulated patients (adjusted hazard ratio [aHR], 2.09 and 3.92) and AP users (aHR, 1.32 and 1.28). Post-stroke warfarin was associated with a significantly increased risk of major bleeding compared with NOACs (aHR, 1.23). Of 769 patients receiving NOACs before stroke and continuing NOACs after stroke, those switching to a different NOAC were associated with significantly higher risk of ischemic stroke (aHR, 2.07) and composite outcomes (aHR, 1.36–1.85) with no difference in intracranial hemorrhage, major bleeding, or mortality compared with those receiving the same NOAC after stroke. Of patients receiving NOACs before stroke, the risks of clinical events were similar between patients taking NOACs alone and those taking NOAC plus AP after stroke. ConclusionNOAC alone after stroke was associated with a better clinical outcome compared with nonanticoagulation, AP, or warfarin. Of patients already taking NOACs before stroke, the addition of AP did not confer additional benefits compared with NOACs alone. A change of NOAC types after stroke was associated with a 2-fold higher risk of ischemic stroke and composite outcomes.

Safety and efficacy of anticoagulant treatment in patients with ovarian vein thrombosis: a systematic review and meta-analysis of observational studies

BackgroundThe role of anticoagulation in ovarian vein thrombosis (OVT) is uncertain. ObjectivesWe aimed to evaluate safety and efficacy of anticoagulant treatment in OVT patients. MethodsA systematic search was conducted in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases up to April 2024. Eligible studies included randomized controlled trials and observational studies enrolling at least 10 adult patients with objectively diagnosed OVT and treated with any anticoagulants. The protocol was prospectively registered in the International Prospective Register of Systematic Reviews (CRD42021270883). ResultsWe included 17 observational studies (621 anticoagulated and 376 nonanticoagulated OVT patients); 9 studies enrolled mainly pregnancy/puerperium-related OVT. Most patients received heparins alone (45.7%) or proceeded to vitamin K antagonists (39.2%). The average treatment duration was ≤3 months in 8 studies (47.1%), >3 to ≤6 months in 6 studies (35.3%), and >6 months in 3 studies (17.6%). In treated patients, mortality rate was 2.43% (95% CI, 0.54%-5.41%; I2 = 53.8%; 12/406 patients; 13 studies), major bleeding was 1.27% (95% CI, 0.48%-2.38%; I2 = 2.5%; 7/583 patients; 15 studies), recurrent venous thromboembolism (VTE) was 3.49% (95% CI, 1.12%-6.95%; I2 = 63.5%; 22/482 patients; 15 studies), and vessel recanalization was 89.4% (95% CI, 74.6%-98.6%; I2 = 80.6%; 163/184 patients; 8 studies). The rate of recurrent VTE in untreated patients was 8.65% (95% CI, 2.61%-17.35%); however, the difference compared with treated patients was not statistically significant (risk ratio, 0.70; 95% CI, 0.36-1.37). At subgroup analyses, the rates of major bleeding and recurrent VTE were 0.80% (95% CI, 0.0-2%.17%) and 3.81% (95% CI, 0.42%-9.63%) in pregnancy/puerperium-related OVT, respectively, and 1.12% (95% CI, 0.32%-2.34%) and 1.78% (95% CI, 0.62%-3.46%), respectively, when analyzing only full-text studies. ConclusionThere is paucity of literature regarding OVT. Our results suggest that anticoagulation is associated with low rates of major bleeding and recurrent VTE.

Utilization and safety of off-label prothrombin complex concentrate (4F-PCC) in a nonsurgical population.

The aim of this study was to evaluate and describe the utilization and safety of 4F-PCC in a nonanticoagulated, nonsurgical patient population at an academic, tertiary care center. This retrospective, single-center chart review evaluated nonanticoagulated adult patients at least 18 years of age who had at least one dose of 4F-PCC administered between January 1, 2017, and September 30, 2022, for a nonsurgical indication. Hemostatic efficacy following 4F-PCC administration was the primary outcome, and secondary outcomes included an assessment of blood product administration, thrombotic events within 30 days post4F-PCC administration, in-hospital mortality, and the length of hospital stay. A total of 59 patients met the inclusion criteria, and 10 patients received 4F-PCC for coagulopathy associated with liver disease, 34 for intracranial hemorrhage (ICH), and 15 for other indications. For the primary outcome of hemostatic efficacy, 17 non-ICH patients (85%) had achieved hemostasis post-4F-PCC, and among the ICH patient population, 18 (64%) did not show expansion on repeat CT post4F-PCC, suggesting hemostasis. Blood product and hemostatic agent usage was frequent, with 72.9% of patients requiring products post-4F-PCC. Acute thromboembolic events occurred in six patients (10.2%), and in-hospital mortality occurred in 55.9% of patients. Off-label 4F-PCC use is common despite a lack of robust guidance for use. Following 4F-PCC administration, blood product use was frequent, the incidence of in-hospital mortality was high, and thromboembolic complications such deep vein thrombosis (DVT), pulmonary embolism (PE), and stroke were reported. Further studies are needed to validate the off-label administration of 4F-PCC in nonanticoagulated patients.

#1313 Dicumarinics and the direct thrombin or factor Xa inhibitors (NOAs) their usefulness in advanced chronic renal disease

Abstract Background and Aims Our population with advanced chronic kidney disease (ACKD), is more prone to thrombotic and hemorrhagic processes so the indication of anticoagulation before the appearance of atrial fibrillation (AF) is complex. Since AF is the most common cardiac arrhythmia, its main complications are thromboembolism and stroke. New treatments are being developed, such as the new oral anticoagulants (NOAs), but their safety in ACKD is still uncertain. To see anticoagulation needs, safety and major adverse effects (major or minor bleeding) in population with ACKD and taking dicumarinics or NOAs. Method Retrospective study of 234 patients followed in our ACKD practice, at least two revisions, with a mean follow-up 25.5 months, in which we recorded cause of anticoagulation, type and major adverse effects. Results 26% of patients have indication for anticoagulation (66 patients), of which 55 remain anticoagulated during follow-up (45% Dicumarinics, 44% NOAs). The indication for anticoagulation was 23% AF (56 patients) and 3% mechanical prostheses (7 patients). Table 1 shows the characteristics of the overall population and the comparison between anticoagulated patients with different types of anticoagulation and non-anticoagulated patients. Non-anticoagulated patients are younger and have less ischemic heart disease, with no differences in the non-anticoagulated population. Throughout follow-up, we found a higher incidence of bleeding with NOAs (compared to the rest) and higher mortality in patients with dicumarinics (compared to the rest). There were no differences in age, sex and ischemic heart disease between the two anticoagulant treatments. Conclusion Our CKD population has a high need for anticoagulation but also a high risk of bleeding. NOAs can be used in ACKD although they are associated with a higher incidence of bleeding than dicumarinics but lower mortality. More studies are needed to conclude which is the best approach for these patients.

ECG and Atrial Appendage Doppler Discordance Is Common in Patients Undergoing Cardiac Surgery: Prospective Study

BackgroundPatients with atrial fibrillation (AF) remain at increased risk of thromboembolism despite apparent maintenance of sinus rhythm with the cause often attributed to periods of asymptomatic AF. Atrial mechanical discordance, with the body of the left atrium (LA) in sinus rhythm and the left atrial appendage (LAA) in AF may also be a contributor. ObjectivesThe purpose of this study was to assess the frequency of electrocardiogram (ECG) rhythm and LAA and/right atrial appendage (RAA) Doppler ejection phenotype (transesophageal echocardiography [TEE]) discordance in patients undergoing cardiac surgery. MethodsA total of 124 patients undergoing coronary artery bypass graft (CABG), CABG and valve surgery, or isolated valve repair or replacement (valve ± CABG) were prospectively studied. Intraoperative surface ECG rhythm strip and TEE were performed before cardiopulmonary bypass. The ECG and TEE LAA/RAA Doppler spectrum were independently classified as sinus or AF. ResultsOf 107 patients (age 65 ± 12 years; 31% female; 65% CABG, 31% valve ± CABG) without a history of AF, 39 (36%) had ECG and LAA and/or RAA discordance (ECG/LAA Doppler discordance, n = 12 [11%]; ECG/RAA Doppler discordance, n = 35 [33%]). There was no significant difference between concordant and discordant groups with regard to age, gender, history of hypertension, diabetes, heart failure, or stroke (all P > 0.05). ConclusionsA large minority of patients without a history of AF undergoing cardiac surgery have ECG/atrial appendage Doppler discordance, a setting that may promote thromboembolism in non-anticoagulated patients. Clinical parameters do not identify patients at increased risk for discordance.

Chronic anticoagulation therapy and acute hip trauma

Regardless of the association between hip fracture surgery and mortality, morbidity and bleeding risks, there are still significant contradictions in various published articles concerning hip fracture surgery outcomes when patients are prescribed anticoagulant medication. The primary objective of this study was to investigate if patients prescribed anticoagulants experienced delayed surgery when compared to non-users. The secondary goal was to investigate if patients prescribed anticoagulants underwent an extended hospital stay and complications such as increased bleeding, mortality and a higher rate of comorbidities when compared to non-users. Data from proximal hip fracture patients were prospectively collected at a level I university trauma center. From 1 January, 2020, through 1 January, 2021, 519 eligible patients were identified. Anticoagulant medication upon admission, time prior to surgery, hospitalized days, 30-day mortality rates, 1-year mortality, blood transfusion requirement and various comorbidities were noted. 222 of the 519 hip fracture patients were prescribed anticoagulants. Of the 222 patients, 75% were females and 25% were males. In total, 46% required a blood transfusion, with no significant differences between the anticoagulated and non-anticoagulated patients. 50% of the anticoagulated group and 42% of the control group required perioperative blood transfusion. Neither the 30-day nor the 1-year mortality rate showed statistically significant differences between the groups. However, the time to surgery and the length of hospital stay was significantly longer in the anticoagulated group. Comorbidities were found in 87% of the patients: in 95% of the anticoagulated group and in 81% of the non-anticoagulated group. Patients prescribed anticoagulants at the time of hip fracture experienced delayed surgery, longer hospital stays and more comorbidities when compared to patients not on anticoagulants. Neither a blood transfusion requirement, 30-day mortality rate nor a 1-year mortality rate showed no significant difference between the two cohorts.

Outcomes of mechanical thrombectomy in anticoagulated patients with acute distal and medium vessel stroke.

Stroke remains a major health concern globally, with oral anticoagulants widely prescribed for stroke prevention. The efficacy and safety of mechanical thrombectomy (MT) in anticoagulated patients with distal medium vessel occlusions (DMVO) are not well understood. This retrospective analysis involved 1282 acute ischemic stroke (AIS) patients who underwent MT in 37 centers across North America, Asia, and Europe from September 2017 to July 2023. Data on demographics, clinical presentation, treatment specifics, and outcomes were collected. The primary outcomes were functional outcomes at 90 days post-MT, measured by modified Rankin Scale (mRS) scores. Secondary outcomes included reperfusion rates, mortality, and hemorrhagic complications. Of the patients, 223 (34%) were on anticoagulation therapy. Anticoagulated patients were older (median age 78 vs 74 years; p < 0.001) and had a higher prevalence of atrial fibrillation (77% vs 26%; p < 0.001). Their baseline National Institutes of Health Stroke Scale (NIHSS) scores were also higher (median 12 vs 9; p = 0.002). Before propensity score matching (PSM), anticoagulated patients had similar rates of favorable 90-day outcomes (mRS 0-1: 30% vs 37%, p = 0.1; mRS 0-2: 47% vs 50%, p = 0.41) but higher mortality (26% vs 17%, p = 0.008). After PSM, there were no significant differences in outcomes between the two groups. Anticoagulated patients undergoing MT for AIS due to DMVO did not show significant differences in 90-day mRS outcomes, reperfusion, or hemorrhage compared to non-anticoagulated patients after adjustment for covariates.

Utilization and safety of off-label prothrombin complex concentrate (four-factor prothrombin complex concentrate) in a surgical population.

The aim of this study is to evaluate and describe the utilization and safety of 4F-PCC in a nonanticoagulated, surgical patient population at an academic, tertiary care center. This retrospective, single-center chart review evaluated nonanticoagulated adult patients at least 18 years of age who had at least one dose of 4F-PCC administered between 1 January 2017 and 30 September 2022 for a surgical or peri-procedural indication. Hemostatic efficacy following 4F-PCC administration was the primary outcome, assessed by subsequent blood product administration and hemoglobin and hematocrit reduction. Secondary outcomes included an assessment of thrombotic events within 30 days post-4F-PCC administration, in-hospital mortality, and the length of hospital stay. A total of 71 patients met the inclusion criteria, with 61 patients receiving 4F-PCC for cardiac surgery and 10 patients for other intraoperative or peri-procedural indications. The mean total 4F-PCC dose was 25.0 U/kg. For the primary outcome of hemostatic efficacy, 81% of patients had excellent hemostasis; however, blood product administration was reported in 95.8% of patients post-4F-PCC. Thromboembolic events occurred in 10 (14.1%) patients and 21.1% of patients expired prior to discharge in the total cohort. Off-label 4F-PCC use in nonanticoagulated patients is reported despite a lack of robust guidance for use. Following 4F-PCC administration, hemostatic efficacy based on hemoglobin and hematocrit changes was observed; however, blood product use was frequent, and 4F-PCC administration was not without risks, including thromboembolic complications such deep vein thrombosis (DVT), pulmonary embolism, and stroke. Further studies are needed to validate the off-label administration of 4F-PCC in nonanticoagulated patients.

The impact of anticoagulant medications on fragility femur fracture care: The hip and femoral fracture anticoagulation surgical timing evaluation (HASTE) study

IntroductionDue to their hypocoagulable state on presentation, anticoagulated patients with femoral fragility fractures typically experience delays to surgery. There are no large, multicentre studies previously carried out within the United Kingdom (UK) evaluating the impact of anticoagulant use in this patient population. This study aimed to evaluate the current epidemiology and compare the perioperative management of anticoagulated and non-anticoagulated femoral fragility fracture patients. MethodsData was prospectively collected through a collaborative, multicentre approach involving hospitals across the United Kingdom. Femoral fragility fracture patients aged ≥60 years and admitted to hospital between 1st May to 31st July 2023 were included. Main outcomes under investigation included time to surgery, receipt of blood transfusion between admission and 48 h following surgery, length of stay, and 30-day mortality. These were assessed using multivariable linear and logistic regression, and Cox proportional hazards models. Only data from hospitals ≥90 % case ascertainment with reference to figures from the National Hip Fracture Database (NHFD) were analysed. ResultsData on 10,197 patients from 78 hospitals were analysed. 18.5 % of patients were taking anticoagulants. Compared to non-anticoagulated patients, time to surgery was longer by 7.59 h (95 %CI 4.83–10.36; p < 0.001). 42.41 % of anticoagulated patients received surgery within 36 h (OR 0.54, 95 %CI 0.48–0.60, p < 0.001). Differences in time to surgery were similar between countries however there was some variation across units. There were no differences in blood transfusion and length of stay between groups (OR 1.03, 95 %CI 0.88–1.22, p = 0.646 and 0.22 days, 95 %CI -0.45–0.89; p = 0.887 respectively). Mortality within 30 days of admission was higher in anticoagulated patients (HR 1.27, 95 %CI 1.03–1.57, p = 0.026). ConclusionsAnticoagulated femoral fragility fracture patients comprise a substantial number of patients, and experience relatively longer delays to surgery with less than half receiving surgery within 36 h of admission. This may have resulted in their comparatively higher mortality rate. Inclusion of anticoagulation status in the minimum data set for the NHFD to enable routine auditing of performance, and development of a national guideline on the management of this growing and emerging patient group is likely to help standardise practice in this area and improve outcomes.

Fibrillatory wave amplitude and thromboembolic risk in non-anticoagulated patients with atrial fibrillation

Background The benefit of oral anticoagulation in atrial fibrillation (AF) is well established for patients at elevated stroke risk, but less clear for those at intermediate risk. We investigated whether analysis of electrocardiogram (ECG) derived fibrillatory waves (F-waves) could help identify patients at risk for stroke and systemic embolism (SSE). Methods The Finnish Cardioversion (FinCV) study included patients not on permanent anticoagulation therapy who underwent cardioversion for an acute AF episode. We identified 739 individuals with a valid ECG and complete follow-up data. The maximum amplitudes of the F-waves in leads II and V1 were manually measured from the pre-procedure ECG. Patients were categorized into fine and coarse F-wave groups. The optimal lead and amplitude threshold for grouping were found in an events per person-years analysis. SSE were identified from the patient medical records until either anticoagulation was prescribed, AF was deemed chronic, the patient had deceased, or the end of follow-up. Results Overall 37 (5.0%) patients suffered SSE during the median follow-up time of 5.4 years (1.9–10.8). Measured from lead V1 the SSE rates per 100 person-years were 1.5 and 0.7 in fine and coarse F-wave groups, respectively. Fine F-waves were observed in 112 (15.2%). Baseline characteristics were similar between the groups. Fine F-wave predicted SSE in a competing risk analysis (SHR 2.34, 95%CI 1.12–4.87, p = .023). Analyses from lead II did not provide significant results. Conclusion Electrocardiographic F-wave amplitude may provide additional information on stroke risk in patients with paroxysmal AF and borderline indications or contraindications for anticoagulation.

Taipan snake venom time has high sensitivity for lupus anticoagulants in non-anticoagulated, triple positive antiphospholipid syndrome patients.

Dilute Russell's viper venom time (dRVVT) and activated partial thromboplastin time (APTT) are the mainstay assays in lupus anticoagulant (LA) detection yet they have limitations, particularly in relation to interferences and specificity. The recently validated Taipan snake venom time (TSVT) screening with ecarin time (ET) confirmatory assays overcome many of those limitations due to the innate specificity engendered from direct prothrombin activation, and insensitivity to the effects of vitamin K antagonists (VKA). The present study aimed to further evidence diagnostic utility of TSVT/ET by performing them in samples from 116 nonanticoagulated patients with established triple-positive antiphospholipid syndrome (APS). Samples were identified in three expert centres who performed dRVVT, APTT and solid phase antiphospholipid antibody assays with reagents from a variety of manufacturers. All samples additionally received TSVT/ET analysis using standardised reagents. Ninety seven of 116 (83.6%) were dRVVT- and APTT-positive, 85/97 (87.6%) of which were TSVT/ET-positive, 9/116 (7.8%) were dRVVT-positive only, 6 of which were TSVT/ET-positive, and 10/116 (8.6%) were APTT-positive only, 5 of which were TSVT/ET-positive. 96/116 TSVT/ET-positivity returned a high sensitivity for LA of 82.8%. Low coefficients of determination revealed weak relationships between LA potency and anticardiolipin and anti-β2-glycoprotein I antibody titres for all three LA assays. TSVT/ET has high sensitivity for the clinically significant LA found in triple positive APS patients. TSVT/ET can establish multiple LA assay positivity in nonanticoagulated patients negative for one of dRVVT or APTT, and is the only assay pairing insensitive to VKAs, the recommended anticoagulation for APS.

Phenotypes and outcomes in non-anticoagulated patients with atrial fibrillation: An unsupervised cluster analysis

Phenotypes and outcomes in non-anticoagulated patients with atrial fibrillation: An unsupervised cluster analysis

Thrombosis recurrence and major bleeding in non-anticoagulated thrombotic antiphospholipid syndrome patients: Prospective study from antiphospholipid syndrome alliance for clinical trials and international networking (APS ACTION) clinical database and repository (“Registry”)

BackgroundLong-term anticoagulant therapy is generally recommended for thrombotic antiphospholipid syndrome (TAPS) patients, however it may be withdrawn or not introduced in routine practice. ObjectivesTo prospectively evaluate the risk of thrombosis recurrence and major bleeding in non-anticoagulated TAPS patients, compared to anticoagulated TAPS, and secondly, to identify different features between those two groups. Patients/MethodsUsing an international registry, we identified non-anticoagulated TAPS patients at baseline, and matched them with anticoagulated TAPS patients based on gender, age, type of previous thrombosis, and associated autoimmune disease. Thrombosis recurrence and major bleeding were prospectively analyzed using Kaplan-Meier method and compared using a marginal Cox's regression model. ResultsAs of June 2022, 94 (14 %) of the 662 TAPS patients were not anticoagulated; and 93 of them were matched with 181 anticoagulated TAPS patients (median follow-up 5 years [interquartile range 3 to 8]). The 5-year thrombosis recurrence and major bleeding rates were 12 % versus 10 %, and 6 % versus 7 %, respectively (hazard ratio [HR] 1.38, 95 % confidence interval [CI] 0.53 to 3.56, p = 0.50 and HR 0.53; 95 % CI 0.15 to 1.86; p = 0.32, respectively). Non-anticoagulated patients were more likely to receive antiplatelet therapy (p < 0.001), and less likely to have more than one previous thrombosis (p < 0.001) and lupus anticoagulant positivity (p = 0.01). ConclusionFourteen percent of the TAPS patients were not anticoagulated at recruitment. Their recurrent thrombosis risk did not differ compared to matched anticoagulated TAPS patients, supporting the pressing need for risk-stratified secondary thrombosis prevention trials in APS investigating strategies other than anticoagulation.

Net clinical benefit of oral anticoagulants in Asian patients with atrial fibrillation based on a CHA2DS2-VASc score

BackgroundThis study was conducted to assess the net clinical benefit (NCB) for oral anticoagulant (OAC) in atrial fibrillation (AF) patients according to the CHA2DS2-VASc score.MethodsPatients with AF were prospectively recruited in the COOL AF Thailand registry from 2014 to 2017. The incidence rate of thromboembolic (TE) events and major bleeding (MB) was calculated. Cox proportional hazards model was used to compare the TE and MB rate in patients with and without OACs in CHA2DS2-VASc score of 0–1 and ≥ 2, respectively. The survival analysis was performed based on CHA2DS2-VASc score. The NCB of OACs was defined as the TE rate prevented minus the MB rate increased multiplied by a weighting factor.ResultsA total of 3,402 AF patients were recruited. An average age of patients was 67.38 ± 11.27 years. Compared to non-anticoagulated patients, the Kaplan Meier curve showed anticoagulated patients with CHA2DS2-VASc score of 2 or more had the lower thromboembolic events with statistical significance (p = 0.043) and the higher MB events with statistical significance (p = 0.018). In overall AF patients, there were positive NCB in warfarin patients with CHA2DS2-VASc score of 3 or more while there were positive NCB in DOACs patients regardless of CHA2DS2-VASc score. Females with CHA2DS2-VASc score of 3 or more had a positive NCB regardless of OACs type. Good anticoagulation control (TTR ≥65%) improved an NCB in males with CHA2DS2-VASc score of 3 or more.ConclusionsAF patients with CHA2DS2-VASc score of 3 or more regardless warfarin or DOACs had a positive NCB. The NCB of OACs was more positive for DOACs compared to warfarin and for females compared to males.

Stroke and bleeding risk in atrial fibrillation with CHA2DS2-VASC risk score of one: the Norwegian AFNOR study.

The benefit of oral anticoagulant (OAC) therapy in atrial fibrillation (AF) and intermediate stroke risk is debated. In a nationwide Norwegian cohort with a non-sex CHA2DS2-VASc risk score of one, this study aimed to investigate (i) stroke and bleeding risk in AF patients with and without OAC treatment, and (ii) the risk of stroke in non-anticoagulated individuals with and without AF. A total of 1 118 762 individuals including 34 460 AF patients were followed during 2011-18 until ischaemic stroke, intracranial haemorrhage, increased CHA2DS2-VASc score, or study end. One-year incidence rates (IRs) were calculated as events per 100 person-years (%/py). Cox regression models provided adjusted hazard ratios (aHRs [95% confidence intervals]). Among AF patients, the ischaemic stroke IR was 0.51%/py in OAC users and 1.05%/py in non-users (aHR 0.47 [0.37-0.59]). Intracranial haemorrhage IR was 0.28%/py in OAC users and 0.19%/py in non-users (aHR 1.23 [0.88-1.72]). Oral anticoagulant use was associated with an increased risk of major bleeding (aHR 1.37 [1.16-1.63]) but lower risk of the combined outcome of ischaemic stroke, major bleeding, and mortality (aHR 0.57 [0.51-0.63]). Non-anticoagulated individuals with AF had higher risk of ischaemic stroke compared to non-AF individuals with the same risk profile (aHR 2.47 [2.17-2.81]). In AF patients at intermediate risk of stroke, OAC use was associated with overall favourable clinical outcomes. Non-anticoagulated AF patients had higher risk of ischaemic stroke compared to the general population without AF with the same risk profile.

Dynamic change in anticoagulation pattern at age 65 years in patients with atrial fibrillation and prior low thromboembolic risk

Abstract Background Atrial Fibrillation (AF) is common in elderly patients. Age ≥65 years is an independent thromboembolic risk factor in patients with AF and is an indication for the initiation of anticoagulant therapy based on CHA2DS2VASc scale. Despite this, it may be controversial to justify an arbitrary cut-off for a continuous variable to determine that risk. Objectives The primary endpoint was to assess whether the initiation of anticoagulation therapy in patients who were 65 years old prevents ischemic stroke events in low thromboembolic risk individuals at baseline (CHA2DS2VASc 0 points in male and 1 in women). Another aim was to evaluate whether there were differences in major bleeding events in this population. Methods We used data from the CardioCHUVI-AF registry that included 16202 patients with a diagnosis of AF from the Vigo Health Area between January 2014 and January 2018 Of these, 861 individuals (5.3%) had low embolic risk at baseline. Eight patients with Hypertrophic Cardiomyopathy, 26 with mechanical prostheses and 3 with mitral stenosis were excluded. Of the remaining 824 patients, 389 (2.4%) ceased to belong to this low embolic risk group due to age (≥65 years) during the follow-up period. Univariate analysis was performed with age ≥65 years to compare the incidence of ischemic stroke and major bleeding events in anticoagulated patients with those in non-anticoagulated patients. Results A total of 389 patients with a diagnosis of AF and initial low embolic risk were followed for 8.1±1.5 years (median 8.9, IQR 7.8-9.0 years). The mean age at the start of follow-up was 60.9±2.7 years. Before the age of 65, 187 patients (48.1%) were anticoagulated. A total of 261 patients were under anticoagulant treatment after turn to 65 years (67.1%, an increase of 19.0% in the rate of anticoagulation). Therefore, 32.9% of the individuals were not anticoagulated despite the fact that they had an indication at that time. In the Kaplan-Meier curves of our study population before reaching 65 years of age, no significant differences were observed in the rate of ischemic stroke events between anticoagulated and non-anticoagulated patients [HR, 1.22; 95%CI 0.41-3.64; p=0.718] or in the rate of major bleeding [HR 1.03, 95%CI 0.36-2.95; p=0.949]. However, in the same population that had already reached 65 years of age at the end of follow-up, statistically significant differences were observed in favor of anticoagulated patients in the incidence of ischemic stroke [HR 0.19, 95%CI 0.05-0.77; p=0.020] without an increase in the rate of hemorrhagic events [HR 0.85, 95%CI 0.32-2.27; p=0.745]. Conclusions Our registry highlights the dynamic nature of the CHA2DS2VASc scale based on age. Thus, patients with a CHA2DS2VASc score of 0 points (1 if they are women) who are close to 65 years should be evaluated periodically, starting anticoagulation therapy at that age.

Thrombin Generation Is Associated with Venous Thromboembolism Recurrence, but Not with Major Bleeding and Death in the Elderly: A Prospective Multicenter Cohort Study.

It is currently unknown whether thrombin generation is associated with venous thromboembolism (VTE) recurrence, major bleeding, or mortality in the elderly. Therefore, our aim was to prospectively study the association between thrombin generation and VTE recurrence, major bleeding, and mortality in elderly patients with acute VTE. Consecutive patients aged ≥65 years with acute VTE were followed for 2 years, starting from 1 year after the index VTE. Primary outcomes were VTE recurrence, major bleeding, and mortality. Thrombin generation was assessed in 551 patients 1 year after the index VTE. At this time, 59% of the patients were still anticoagulated. Thrombin generation was discriminatory for VTE recurrence, but not for major bleeding and mortality in non-anticoagulated patients. Moreover, peak ratio (adjusted subhazard ratio 4.09, 95% CI, 1.12-14.92) and normalized peak ratio (adjusted subhazard ratio 2.18, 95% CI, 1.28-3.73) in the presence/absence of thrombomodulin were associated with VTE recurrence, but not with major bleeding and mortality after adjustment for potential confounding factors. In elderly patients, thrombin generation was associated with VTE recurrence, but not with major bleeding and/or mortality. Therefore, our study suggests the potential usefulness of thrombin generation measurement after anticoagulation completion for VTE to help identify among elderly patients those at higher risk of VTE recurrence.