Anticoagulant Therapy Research Articles

Beyond the Usual Suspects: Unmasking a Rare Pulmonary Co-Infection

This case report presents a 33-year-old male farmer with community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) pneumonia complicated by Leptospirosis. The patient presented with a 2.5-month history of high-grade fever, chest pain, and weight loss. Investigations revealed multiple cavitary lesions in bilateral lungs. Blood cultures were positive for MRSA, and ELISA for leptospira was positive. The patient was successfully treated with vancomycin and anticoagulation therapy and discharged.

Suprarenal interrupted inferior cava with azygos continuation in a patient with pulmonary embolism: a case report

Abstract Background Interrupted inferior vena cava (IVC) is a rare developmental defect characterised by azygos continuation following failure of fusion of one or more of the component parts of the embryological IVC. It occurs in approximately one in 5000 of the general population. It is usually an isolated finding and is generally asymptomatic. Case Summary A 42-year-old patient presented for further clarification of syncope with a four-day history of persistent exertional dyspnoea. Computed Tomography (CT) revealed a central pulmonary artery embolism on both sides, with prominent azygos and hemiazygos veins and paravertebral collaterals. For further clarification, a magnetic resonance imaging (MRI) scan was performed, where hypoplasia or stenosis of the inferior suprarenal vena cava was noted. There were collaterals of the azygos and hemiazygos veins. The finding was consistent with the picture of a venous abnormality in the sense of an "interrupted IVC (suprarenal) with azygos continuation." Discussion In the case of an isolated interrupted IVC, the patient is usually asymptomatic, and the vascular anomaly itself does not mandate any treatment. This variation should be considered, especially in young patients with deep venous thrombosis (DVT) when no other reason for thromboembolism is evident. To prevent vascular events such as DVT or pulmonary embolism, lifelong anticoagulation therapy is recommended. An interrupted IVC can also cause procedural difficulties during right heart catheterisation, electrophysiological studies, cardiopulmonary bypass surgery, femoral vein catheter advancement, IVC filter placement, and temporary pacing through the transfemoral route.

The initial high-dose versus maintenance-dose anticoagulation therapy with direct oral anticoagulants for cancer-associated venous thromboembolism: from the COMMAND VTE Registry-2

Abstract Background/Introduction Initial high-dose anticoagulation therapy with rivaroxaban and apixaban has been a standard treatment for venous thromboembolism (VTE), although there could be concerns of an increased risk of bleeding events especially among high bleeding-risk patients including those with active cancer. Purpose The present study aimed to evaluate the clinical outcome of initial high-dose anticoagulation therapy comparing to maintenance-dose anticoagulation therapy in patients with cancer-associated VTE using propensity score-matching analysis. Methods The COMMAND VTE Registry-2 is a multicenter registry enrolling 5197 consecutive acute symptomatic VTE patients among 31 centers in Japan between January 2015 and August 2020. Among 1507 patients with cancer-associated VTE, we evaluated 180-day clinical outcomes before discontinuation of anticoagulation therapy using a 1:1 propensity score-matching model with 21 risk-adjusting variables Results After the propensity score-matching, we enrolled 324 patients with initial high-dose anticoagulation therapy and 324 patients with initial maintenance dose anticoagulation therapy. Of patients with initial high-dose anticoagulation therapy, rivaroxaban and apixaban were administered in 198 and 126 patients, respectively. Of those with initial maintenance-dose anticoagulation therapy, rivaroxaban, apixaban, and edoxaban were administered in 34, 46 and 244 patients, respectively. The median durations of initial high-dose anticoagulation therapy were 18 [IQR: 15-21] days for rivaroxaban and 7 [IQR: 7-7] days for apixaban. In the current study population, the mean age was 67±12 years, 346 were women, and the mean body weight was 58±12 kg. There was no significant difference in the distribution of gastrointestinal cancer such as stomach and colorectal cancer between the 2 groups (4.6% vs. 4.9%, P=1.0, 8.3% vs. 11.4%, P=0.22). The cumulative 180-day incidence of discontinuation of anticoagulation was not significantly different between the 2 groups (27.8% vs. 30.5%, P=0.50). There were no significant differences in the cumulative 180-day incidences of recurrent VTE (3.1% vs. 1.0%, P=0.08), nor major bleeding (8.1% vs. 7.0%, P=0.66), nor all-cause death (25.1% vs. 21.6%, P=0.33) between the 2 groups. There were also no significant differences in the cumulative 180-day incidences of all clinically relevant bleeding (14.9% vs. 13.3%, P=0.72), gastrointestinal bleeding (8.4% vs. 5.4%, P=0.15), nor major gastrointestinal bleeding (5.4% vs. 2.7%, P=0.10). Conclusions There was no signal of an increased risk of recurrent VTE in the initial maintenance-dose anticoagulation therapy. Considering a numerically slightly higher incidence of gastrointestinal bleeding in the initial high-dose anticoagulation therapy for cancer-associated VTE, the initial maintenance-dose anticoagulation therapy could be a potential treatment option for selected patients including patients at a high risk of gastrointestinal bleeding.Study flow chartResults

Antithrombotic treatment in univentricular heart

Abstract Background Univentricular heart (UVH) corrected with Fontan surgery may be associated with an increased risk of thrombosis. Data regarding optimal thrombotic prevention strategy after Fontan surgery in patients with UVH is scarce, and guidelines for antithrombotic treatment are not yet available. Purpose The aim was to evaluate the prevalence of antithrombotic treatments and their relation to mortality in patients with Fontan circulation. Methods A total of 5,075 patients with UVH were identified using data from the Swedish National Patient Register, the Cause of Death Register, and the National Prescribed Drug Register. Patients with UVH born in Sweden between 1970 and 2017 who underwent Fontan surgery were included. The study population was divided into three groups based on medication: anticoagulation therapy, antiplatelet therapy, and no therapy. Incidence rate (IR) was reported per 1000 person-years and calculated as the total number of deaths divided by total follow-up time. Confidence interval (CIs) for IR was estimated with Poisson regression. Kaplain-Meier was used to estimate the survival probability of 95% for UVH. The Stratified Cox proportional hazards model was used to estimate hazard ratios (HR) with 95% CI. Results The total cohort consisted of 864 patients of which 280 individuals (32%) had hypoplastic left heart syndrome (HLHS). The median follow-up time was 14.4 (IQR 3.9;24.9) years, maximum follow-up time was 47 years. Out of all the patients, 36% received no anticoagulation or antiplatelet therapy. Among those who did receive therapy, 75% were treated with antiplatelets. The patients who had no therapy had a higher mortality rate. During long-term follow-up, patients with UVH had higher survival rates when treated with antiplatelets. Conclusion Antithrombotic therapy, in particular antiplatelet therapy, was associated with the highest survival in patients with UVH as compared to no treatment. Our data suggest that antithrombotic treatment, and in particular antiplatelet treatment, could be considered in patients with UVH.Survival with Antithrombotic treatment

Evaluation of bleeding events in a cohort of patients with transthyretin cardiac amyloidosis

Abstract Introduction and purpose transthyretin amyloidosis is an infiltrative disease with several comorbidities, including bleeding. The aim of this study was to evaluate the incidence of bleeding in patients with transthyretin amyloidosis and the underlying risk factors that promote bleeding. Methods a retrospective observational study was conducted on a cohort of patients with transthyretin amyloidosis diagnosed between 2016 and 2023 according to the diagnostic criteria of the Working Group on Myocardial and Pericardial Diseases of the European Society of Cardiology. Bleeding risk was calculated according to HAS-BLED score and bleeding events at follow-up were analysed. Results 184 patients were diagnosed with a median age of 84 years [IQR 79-8], 154 (8%) males. 123 patients (67%) were on anticoagulant therapy. 91 patients (50%) had a bleeding event, with a total of 189 events recorded and a median time from transthyretin amyloidosis diagnosis to bleeding of 10 months [IQR 6-14]. The most frequent bleeding sites were gastrointestinal (32%) and cutaneous (22%). 35 patients (39%) had a haemorrhage which fulfilled severe bleeding criteria and 4 patients died of haemorrhagic causes. As a consequence of bleeding, 6 atrial appendage closure were indicated and anticoagulation therapy was modified in 15 individuals. The incidence rate of haemorrhage was 50 bleeds per 100 patient-years and 58 per 100 patient-years in patients on anticoagulant treatment. Anticoagulant therapy resulted in a 3,5-fold raise in bleeding (95% CI 2-7) and a punctuation ≥2 in HAS-BLED score increased haemorrhages 4,6 times (95% CI 2-9), with higher rates of bleeding the higher the score on the scale. Conclusions bleeding is a frequent complication in transthyretin amyloidosis, with a higher risk in those individuals with anticoagulant therapy or with a HAS-BLED score ≥2. Subsequently, it should be considered in the follow-up both haemorrhagic risk and anticoagulant treatment, with the aim of implementing strategies to reduce the bleeding risk.

Temporal trends in antithrombotic therapy following transcatheter aortic valve implantation in denmark

Abstract Background A number of randomized clinical trials have examined the use of antithrombotic therapy after transcatheter aortic valve implantation (TAVI), and guidelines have changed over time. Yet, data from clinical practise patterns are lacking and it is important to evaluate adherence to guideline recommendations over time. Purpose This study aims to evaluate the temporal use of antithrombotic therapy after TAVI in Denmark. Methods A nationwide Danish cohort of patients undergoing first-time TAVI from 2008 to 2017 were identified from Danish nationwide registries. Patients were categorized into four groups according to data on prescription filling of antithrombotic therapy within a three-months period post-TAVI: i) No antithrombotic therapy, ii) single antiplatelet therapy (SAPT), iii) dual antiplatelet therapy (DAPT), or iv) anticoagulant therapy. The use of antithrombotic therapy post-TAVI was examined for each year from 2008 to 2017. Results We identified 3187 patients undergoing first-time TAVI, among whom 120 (3.8%) did not receive any antithrombotic therapy, 715 (22.4%) were prescribed SAPT, 1244 (39.0%) were on DAPT, and 1108 (34.8%) were treated with anticoagulant therapy at three months post-TAVI. Patients without antithrombotic therapy were more often men (64.2%) and were more likely to have a history of malignancy (23.3%) compared with the other treatment groups. Patients who received oral anticoagulation had a higher burden of atrial fibrillation (75.7%). The proportion of patients with atrial fibrillation remained stable over time. During the first decade of TAVI, there was a shift in the antithrombotic treatment pattern: no therapy was ranging from 1.1% to 6.6%, SAPT from 19.1% to 29.4%, while DAPT decreased from 51.0% to 31.2% and anticoagulant therapy increased from 21.6% to 39.8% (Figure 1). Conclusion During the first decade of TAVI, antithrombotic therapy patterns post-TAVI changed substantially, such that the use of dual antiplatelet therapy decreased over time, while the use of anticoagulant therapy increased. Since atrial fibrillation remained stable over time, the increase in anticoagulant therapy is most likely due to changes in guidelines for management of atrial fibrillation in 2010. These findings show the evolving treatment patterns in the first decade of TAVI, which reflects the recommendations from clinical trials and guidelines for the management of antithrombotic therapy for patients with TAVI.

Application of DOAC Score for the risk-stratification of major bleeding in patients with venous thromboembolism on direct oral anticoagulants: insight from the COMMAND VTE Registry-2

Abstract Background/Introduction Bleeding complications are still a major concern in anticoagulation therapy for venous thromboembolism (VTE), even in the direct oral anticoagulant (DOAC) era. Thus, the risk stratification of bleeding during anticoagulation therapy is essential, although most of currently available bleeding risk scores have been developed from patients receiving vitamin K antagonists, which could have limited validity in those receiving DOACs. Very recently, the DOAC Score has been developed to predict major bleeding in patients with atrial fibrillation on DOACs; however, the score has not yet been validated in patients with VTE. Purpose The present study aimed to evaluate the usefulness of the DOAC Score in patients with VTE, using a large-scale multicenter observational database of patients with VTE. Methods The COMMAND VTE Registry-2 is a multicenter registry enrolling 5197 consecutive acute symptomatic VTE patients among 31 centers in Japan between January 2015 and August 2020. The present study population was consisted of 3539 patients with VTE who received DOACs and had a calculated DOAC Score. The eligible patients were classified into 5 risk categories: very low (score 0–3), low (score 4–5), moderate (6–7), high (score 8–9), and very high (score ≥10). We used the Kaplan-Meier method to estimate the cumulative incidence and assessed the discriminatory ability of the DOAC Score for major bleeding at 1 year by calculating the area under the receiver operating characteristic curve. We also assessed the discriminatory ability of the VTE-BLEED and RIETE scores. Results In the present study population, the very low-risk group accounted for 1437 patients (41%), low-risk group for 828 (23%), moderate-risk group for 812 (23%), high-risk group for 326 (9.2%), and very high-risk group for 136 (3.8%). The proportion of anemia was highest in the very high-risk group (71%) and lowest in the very low-risk group (47%). The prevalence of active cancer was highest in the low-risk group (36%) and lowest in the very high-risk group (18%). During the first year of anticoagulation therapy, major bleeding occurred in 180 patients. The cumulative 1-year incidence of major bleeding seemed to be different according to the 5 groups, but the risks could not be well-stratified (Figure 1). The discriminating power of the DOAC Score was relatively low with a C-statistic of 0.52 (95% CI, 0.48–0.57) (Figure 2), while those of VTE-BLEED and RIETE scores were modest with C-statistics of 0.66 (95% CI, 0.60–0.73) and 0.67 (95% CI, 0.64–0.71), respectively. Conclusions The risk of 1-year major bleeding on DOACs in patients with VTE was not well-stratified according to the risk categories by the DOAC Score, which might suggest that patients with VTE have different risk factors for bleeding on DOACs as compared to those with atrial fibrillation. A new bleeding risk score for DOAC specifically in patients with VTE would be warranted in the future.Figure 1Figure 2

Silent cerebral microvascular disease and longitudinal risk of cognitive decline in atrial fibrillation

Abstract Background A relationship between silent stroke and cognitive disorder has recently been suggested in patients with nonvalvular atrial fibrillation (NVAF). This research is an exploratory research study to investigate the occurrence of asymptomatic cerebrovascular disorders with NVAF. Methods The SKAF (Silent cerebral microvascular disease and longitudinal risK of cognitive decline in Atrial Fibrillation) study is a prospective, investigator-initiated, multicenter, observational study of Japanese patients with NVAF aged 60 years or older. We had planned to enroll two hundred NVAF patients with no history of symptomatic stroke or dementia, and an anticoagulant therapy with edoxaban is being performed or an anticoagulant therapy is not being performed, and one hundred patients with sinus rhythm, for comparison. We collected patient characteristics, clinical course, the data of head MRI test and cognitive function test (Montreal Cognitive Assessment (MoCA)) at the baseline and the 24 months follow-up. The primary endpoint was the composite of silent ischemic stroke and micro-bleeding over a 24-month follow-up period. The secondary endpoint was cognitive decline over a 24-month follow-up period. Results The study was started in October 2016, with a planned 2-year recruitment period. As of January 31, 2018, a total of 326 patients were enrolled. Of those, 99 patients with sinus rhythm (SR group) and 214 patients with NVAF (NVAF group) were analyzed (male, 193 (62%) patients; age, 72.2±6.5 years). 156 of 195 (80%) patients with NVAF received the anticoagulant therapy with edoxaban. There was no significant difference of the primary composite for the endpoints between two groups (17.4% versus 17.4%; p=1.00). The incidences of silent ischemic stroke and micro-bleeding in SR and NVAF groups over a 24-month follow-up period were 9.3% and 10.8% (p= 0.833), and 8.1% and 9.2% (p=1.00), respectively. The NVAF group exhibited a significantly larger decline in cognition changes in MoCA score than SR group (-0.830 versus 0,000; p=0.0131). Notably, NVAF was found to be associated with cognitive decline. Conclusion The SKAF registry provided an equivalent risk of silent cerebral microvascular disease in patients with SR and NVAF. Clinically, NVAF had an impact on cognitive decline.

Life-Threatening Spontaneous Hematoma in Unusual Sites in Patients with COVID-19 on Anticoagulant Therapy: A Case Series

Thromboembolic manifestations are a common phenomenon in patients affected by corona virus (SARS CoV-2). Recent studies have shown that patients with acute renal failure are also at a greater risk of venous and arterial thromboembolism, 15-30% in ICU, and 7% inpatient care. However, frequently unjudicial use of anticoagulants may develop severe life-threatening hematoma. In our hospital settings we had a dedicated COVID Unit with a Hemodialysis facility. Our Nephrology department had managed 381 patients being COVID positive along with renal impairment from March 2020 to January 2022. Among these patients, four patients developed spontaneous non traumatic hematoma in unusual sites. On admission all the patients received treatment according to our national guidelines for COVID-19. Cases: It is a retrospective analysis in a single-centered hospital. Four cases with confirmed COVID-19 with acute kidney injury and on anticoagulant therapy had developed sudden concealed bleeding. These patients had no previous history of anticoagulant therapy before admission. Case 1 developed hemorrhage in Right lower anterior paramedian deep parietal wall of abdomen, Case 2 had hematoma in retroperitoneal space and in lower third of Iliopsoas, Case 3 developed hemorrhage in left cerebral hemisphere, Case 4 had Intramuscular Hematoma in left rectus abdominis. Out of these four patients two of them required Hemodialysis and one of them went into shock. All patients included were male. The mean age was 57±19.64years. All the four patients were initially managed conservatively with keen monitoring and with proper volume resuscitation, blood transfusion and discontinuation of the anticoagulants. Three of the patients survived with conservative management and one patient died due to sudden massive cardiac arrest. The use of therapeutic anticoagulant can increase the risk of bleeding in atypical sites and may exhibit higher patient death with COVID-19 if not identified at early stage. So a risk-benefit ratio of usage of anticoagulants should be kept in mind and further clinical trials needed to justify its random use in COVID-19. J Bangladesh Coll Phys Surg 2024; 42: 393-400

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

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

Temporal trends in clinical outcomes in heart failure patients with and without atrial fibrillation: a nationwide study from 1997-2018

Abstract Background Given the many advances in treating heart failure (HF) and atrial fibrillation (AF) separately over the past decades, it remains unclear how the prognosis of patients diagnosed with both conditions has changed over time. Purpose We aimed to investigate the temporal trends in all-cause mortality, HF hospitalisation, and stroke from 1997 to 2018 in patients diagnosed with both HF and AF. Methods From Danish nationwide registries, we identified 152,059 patients with a first-time HF-diagnosis from 1997 to 2018. Patients were categorised into groups based on their AF status: prevalent AF (n=34,734), new-onset AF (n=12,691), and absence of AF (n=104,634). Patients were further subdivided into four year groups (1997-2001, 2002-2006, 2007-2012, 2013-2018), based on the year of HF onset. The primary outcome of interest was the absolute five-year risk of all-cause mortality, and key secondary outcomes were HF hospitalisation and stroke, investigated using the Aalen-Johansen estimator, accounting for competing risk of death. Results Between 1997 and 2018 the proportion of patients with new-onset HF and prevalent AF increased from 17.0% (n = 6,372) to 27.7% (n = 11,569), while those with concurrent new-onset AF increased from 7.7% (n = 2,884) to 8.1% (n = 3401). Contrary, the proportion of patients decreased among those with no AF from 75.3% (n = 28,235) to 64.2% (n = 26,850). The five-year risk of all-cause mortality decreased from 69.1% (95% CI): 67.9%-70.2%) to 51.3% (49.9%-52.7%), 62.3% (60.5%-64.4%) to 43.0% (40.5%-45.5%), and 61.9% (61.3%-62.4%) to 36.7% (35.9%-37.6%) for the prevalent AF, new-onset AF, and no AF group, respectively (Figure 1). The five-year risk of HF hospitalisation went from 33.3% (32.1%-34.4%) to 30.3% (29.2%-31.4%) in the prevalent AF group, from 25.8% (24.2%-27.4%) to 29.6% (27.7%-31.5%) in the new-onset AF group, and from 28.4% (27.8%-28.9%) to 28.0% (27.2%-28.6%) in the no AF group. The five-year risk of stroke decreased from 8.5% (7.8%-9.1%) to 5.0% (4.4%-5.5%) in the prevalent AF group, 8.2% (7.2%-9.2%) to 4.6% (3.7%-5.5%) in the new-onset AF group, and 6.3% (6.1%-6.6%) to 4.9% (4.6%-5.3%) in the no AF group (Figure 2). Simultaneously, the proportion of patients prescribed anticoagulant therapy within 90 days after HF onset increased from 42.7% to 93.1% in patients with prevalent AF and 41.9% to 92.5% in patients with new-onset AF. Conclusion From 1997 to 2018, we observed an increase in patients with HF and coexisting AF. The five-year risk of mortality and stroke decreased across all patient groups regardless of AF-status. Additionally, prescriptions of anticoagulation therapy increased, and stroke risk in patients with HF and AF was reduced to similar levels as patients with HF without AF at the end of the study period.Figure 1 - Mortality in HF patientsFigure 2 - Stroke risk in HF patients

Anticoagulation status and left atrial appendage occlusion indications in hospitalized cardiology patients with atrial fibrillation: a Hellenic Cardiorenal Morbidity Snapshot (HECMOS) sub-study

Abstract Background Proper use of oral anticoagulants is crucial in the management of non-valvular atrial fibrillation (NVAF) patients. Left atrial appendage occlusion (LAAC) may be considered for stroke prevention in patients with NVAF and contraindications for long-term anticoagulant treatment. Purpose We aimed to assess the anticoagulation status and LAAC indications in patients with NVAF from HECMOS (Hellenic Cardiorenal Morbidity Snapshot) survey. Methods HECMOS was a nationwide snapshot survey of cardiorenal morbidity in hospitalized cardiology patients. HECMOS used an electronic platform to collect demographic and clinically relevant information from all patients hospitalized on March 3, 2022, in 55 different cardiology departments. In this substudy, we included patients with known AF without mechanical prosthetic valves and moderate to severe mitral valve stenosis. Patients with poor adherence to anticoagulants, high bleeding risk, previous major bleeding, and previous stroke were considered candidates for LAAC. Results Two hundred fifty-six patients (mean age 76.6±11.7, 148 males) were included in our analysis. Most of them (n=159; 62%) suffered from persistent AF. Mean CHA 2 DS 2 - VASc score was 4.28±1.7, while mean HAS-BLED score was 1.47±0.9. Three out of 3 patients with a CHA 2 DS 2 -VASc 0 or 1 (female) received improperly anticoagulants. Sixteen out of 18 patients with a CHA 2 DS 2 -VASc 1 or 2 (female) received anticoagulants. Thirty-three out of 235 patients with a CHA 2 DS 2 -VASc > 1 or 2 (for female) did not receive improperly anticoagulants. Among 221 under anticoagulant therapy, 191 (86.4%) received non-vitamin K antagonist oral anticoagulants (NOACs) and 30 (13.6%) received vitamin K antagonists. Relative indications for LAAC were present in 77 patients with NVAF (53 had only one risk factor, while 22 had two and 2 patients had three concurrent risk factors). In detail, 15 reported poor or no adherence to the anticoagulant therapy, 17 patients had a history of major bleeding, 36 had a prior stroke and 35 had a HAS-BLED score ≥3. No LAAC treatment was recorded. Conclusion Αnticoagulation status was nearly optimal in a high thromboembolic risk population of cardiology patients, mainly treated with NOACs. Three out of ten AF patients should be screened for LAAC.Anticoagulation by thrombotic riskPotential LAAC candidates

Risk of embolic events in patients with Chagasic Cardiomyopathy and Atrial Fibrillation despite antithrombotic therapy: is anticoagulation enough?

Abstract Background Chagasic cardiomyopathy (CC) differs from other heart failure causes in multiple aspects, highlighting the risk of systemic embolisms. However, few studies have evaluated the risk of embolic events in anticoagulated patients with CC compared to other cardiomyopathies. Objective We aimed to analyze the incidence of systemic embolisms in a cohort of anticoagulated patients diagnosed with atrial fibrillation (AF) with and without CC. Methods A retrospective cohort study was conducted at a fourth-level hospital from 2014-2020. All patients diagnosed with cardiomyopathy of any etiology and AF on an anticoagulation regimen were included. The primary outcome was the incidence of embolic events. A survival analysis was performed using adjusted Cox proportional hazard models. A p-value of <0.05 was considered significant. All statistical tests were two-tailed. Results 149 anticoagulated patients with cardiomyopathy were evaluated (median age: 71 years; women: 30.20%). The cumulative incidence of embolic events was significantly higher in patients with CC (17.50%) compared to those with other cardiomyopathies (4.95%), despite that the latter had a substantially higher CHA2DS2-VASc score (p=0.013). After multivariate analysis, patients with CC had a significantly higher risk of embolic events regardless of the CHA2DS2-VASc score and the anticoagulant prescribed (HR 5.65. 95% CI 1.46-21.83; p=0.012). Conclusions CC was associated with a significantly higher risk of embolic events despite anticoagulation therapy in both groups. More research is required to understand the origin of this risk observed to translate this knowledge into specific indications for anticoagulation for patients with CC.Cumulative incidence of embolic events

The association between steroid use and recurrent venous thromboembolism: from the COMMAND VTE Registry-2

Abstract Background It is well known that use of oral steroids is a risk factor for development of venous thromboembolism (VTE). However, the impact of use of oral steroids on VTE recurrence has not been fully evaluated in the era of direct oral anticoagulants (DOAC), which has been a clinically relevant issue in the decision-making of anticoagulation strategies for patients who need oral steroids after VTE diagnosis. Purpose We aimed to investigate long-term clinical outcomes in VTE patients treated with oral steroids after VTE diagnosis in the DOAC era. Methods The COMMAND VTE Registry-2 is a multicenter registry enrolling 5,197 consecutive acute symptomatic VTE patients among 31 centers in Japan between January 2015 and August 2020. The current study population were divided into 2 groups according to the use of oral steroids after VTE diagnosis; the steroid group and the non-steroid group. We compared clinical characteristics, management strategies, and outcomes including recurrent VTE, major bleeding and all-cause death, between the 2 groups. Results Patients with steroids and those without accounted for 693 (13%) and 4,504 (87%), respectively. Patients with steroids more often had chronic kidney disease (29% vs. 18%, P<0.001), autoimmune disease (50% vs. 5.4%, P<0.001), thrombocytopenia (7.7% vs 4.9%, P=0.002), and anemia (64.4% vs 54.1%, P<0.001), whereas there was no significant difference in the mean age (68.5 vs. 67.6 years old, P=0.16), the prevalence of women (62% vs 58%, P=0.06), active cancer (30% vs. 29%, P=0.42), and history of VTE (8.4% vs 6.8%, P=0.12) between the 2 groups. The cumulative 5-year incidence of discontinuation of anticoagulation therapy were not significantly different between the 2 groups (61.5% vs. 58.5%, log-rank P=0.16). The cumulative 5-year incidences of recurrent VTE nor major bleeding were not significantly different between the 2 groups (10.4% vs. 9.4%, log-rank P=0.55; 16.9% vs. 13.3%, log-rank P=0.16, respectively). Even after adjusting confounders, the risks of recurrent VTE nor major bleeding were not significantly different (adjusted hazard ratio = 0.97, 95% confidence interval = 0.65-1.45, P = 0.89; adjusted hazard ratio = 1.12, 95% confidence interval = 0.84-1.50, P = 0.44). The cumulative 5-year incidences of all-cause death was significantly different between the 2 groups (44.2% vs. 30.2%, log-rank P<0.001). Even after adjusting confounders, the risk of all-cause death remained significantly different (adjusted hazard ratio = 1.82, 95% confidence interval = 1.56-2.12, P<0.001). Conclusions Use of oral steroids after VTE diagnosis was not significantly associated with an increased risk of VTE recurrence in the DOAC Era, which might suggest that there could be no major concerns on an increased risk of recurrent VTE with oral steroids after VTE diagnosis under appropriate anticoagulation therapy.

The triglyceride-glucose index is a marker of thromboembolic events in atrial fibrillation patient under oral anticoagulation therapy

Abstract Background Atrial fibrillation (AF) increases the risk of stroke and thromboembolism; and appropriate risk stratification is central for better targeted patient management. The triglyceride-glucose (TyG) index indirectly assesses insulin resistance, and has been associated with cardiovascular risk. Purpose To investigate whether the TyG index could be a biomarker for assessing the risk of thromboembolic events in patients with AF. Methods We performed an observational prospective cohort study including outpatients diagnosed with AF starting vitamin K antagonist (VKA) or direct-acting oral anticoagulants (DOAC) therapy from January, 2016 to November, 2021. The primary endpoint was a combination of thromboembolic events, considered as the composite of myocardial infarction, and/or venous thromboembolism, and/or ischemic stroke/transient ischemic attack, over 2 years of follow-up. The TyG index was calculated as the natural logarithm (Ln) of the product of baseline plasma glucose and triglyceride using the following formula: Ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)]/2. Patients were stratified into tertiles according to their TyG index (ie. first tertile: TyG index <4.59; second tertile: TyG index 4.59-4.83; third tertile: TyG index >4.83). Results We included 2907 patients (median age 77 [70-83] years; 52.5% female). The median TyG index was 4.71 (4.53-4.91), and 34% (989) where in the third tertile of TyG index. During a follow-up of 2 years, 209 (7.2%) patients suffered a thromboembolic event. Compared to patients in the first or second tertiles of TyG index, patients in the third tertile had an increased annual event rate of thromboembolic events (3.40 per 100 patient-years vs. 4.76 per 100 patient-years, p=0.043; and 3.41 per 100 patient-years vs. 4.76 per 100 patient-years, p=0.044), and higher incidence rate ratio (1.41 [95% CI 1.01-1.98], p=0.044 vs. first tertile; 1.40 [95% CI 1.01-1.97], p=0.044 vs. second tertile). Cox regression analyses adjusted for several risk factors demonstrated that the TyG index was an independent predictor for thromboembolic events (aHR 1.82; 95% CI 1.15-2.89; p=0.011). Patients in the third tertile of TyG index presented a 64% higher risk of thromboembolic events (aHR 1.64; 95% CI 1.17-2.29; p=0.004) (Table), with significantly lower event free survival (log-rank test p-value = 0.016) (Figure). Conclusions In this real-world cohort of AF patients under oral anticoagulation therapy, elevated TyG index was an independent risk factor for thromboembolic events. The TyG index is a simple, low-cost indicator, that could be used as a screening tool in everyday clinical practice.

Anticoagulation control challenges in patients with rheumatic heart disease and mechanical heart valves operated at a cardiac surgery center in a low-income country

Abstract Background Rheumatic heart disease (RHD) prevalence is very high in many low-income countries and valve replacement surgery can sometimes be the only available therapeutic strategy for the affected patients. Mechanical valves require lifelong anticoagulation and this can be very challenging in many poor countries where several barriers to effective anticoagulation monitoring and management are faced. Methods This is a retrospective study on 145 patients with RHD who underwent valve replacement surgery at a cardiac surgery center (CSC) in a low-income country between 2001 and 2022. The study aimed to evaluate the effectiveness of anticoagulation treatment to prevent thromboembolic events in patients with RHD with mechanical valves. The patients’ information such as social and demographic data, clinical features, surgical data and international normalized ratio (INR) records were collected and analyzed. Descriptive statistics were applied to the data and expressed as mean with standard deviation or simple frequencies and percentages. Results The mean age of the operated patients was 25.9 years (± 12.6) and 60% of them were female. Most of the patients (54%) were able to monitor their anticoagulation at the center and 8.2% of them monitored it in other hospitals. Three percent (3%) of the patients use a portable device to monitor their INR. These devices are provided by the CSC to help patients that live in distant provinces and are unable to go to the capital regularly. The device is held by one patient that is a focal point and helps monitor the INR of the other patients living in the same province. The INR results are communicated to the CSC by telephone text message. Seven percent (7%) of the operated patients haven’t monitored their INR for more than one year and 24.8% of them were lost to follow-up. Sixty-four percent (64%) of the patients who monitor their INR at the center have an optimal control of their anticoagulation therapy. Most of the patients that were lost to follow-up (N=20) and most of the patients that haven’t checked their INR for more than one year (N=7) are patients who had aortic valve replacements. At least 20% of the patients that live in capital of the country and close to the CSC don’t monitor their anticoagulation regularly. Conclusion The surgical outcomes in RHD patients who undergo mitral valve repair are usually satisfactory. However, valve replacement is often the only feasible alternative and anticoagulation monitoring and management in these patients can become a serious problem especially to those coming from areas with limited resources. Illiteracy and poverty play a major role as barriers to effective monitoring of anticoagulation therapy. Efforts must be made to increase access to facilities where INR can be monitored. Our experience showed us that providing portable devices for INR monitoring to the patients living in remote areas can be a favorable short-term solution.

Comparative discontinuation and non-bleeding side effects of Clopidogrel, Prasugrel and Ticagrelor in patients with acute coronary syndromes; a Network Meta-analysis of Randomized Controlled Trials

Abstract Background P2Y12 receptor inhibitors are highly effective treatment options following ACS. However, premature discontinuation compromises their effectiveness. Although extensive literature exists, the clinical assessment of their adherence remains controversial, requiring definitive investigation. Purpose To evaluate treatment discontinuation and non-bleeding adverse effects associatedwith platelet P2Y12 receptor inhibitors in individuals post-ACS through network meta-analysis. Methods Data Sources: MEDLINE, Embase, Cochrane, and clinicaltrials.gov to May 2021 and later updated to October 2022. Study Selection and Outcomes: Reviewers identified RCTs that enrolled patients post-ACS taking Clopidogrel, Ticagrelor, and Prasugrel. Exclusions included non-ACS indications, anticoagulation therapy, observational studies, and crossover designs. The primary outcomesincludedoverall treatment discontinuation, treatment discontinuation attributed to side effects, and dyspnea. Secondary outcomes included bradycardia and atrial fibrillation. Data Extraction and Synthesis:This network meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, employing frequentist random-effects models. The GRADE (Grading of Recommendations Assessment, Development, and Evaluation) framework was utilized to assess the certainty of evidence. Results With 139,343 participants in 32 RCTs, the overall treatment discontinuation rate across all studies was 16.57% out of a total of 137,897 participants. Ticagrelor was associated with increased risk for overall treatment discontinuation compared to Clopidogrel (RR, 1.34; 95% CI, 1.19 to 1.49; P<0.0001), Prasugrel (RR, 1.23; 95% CI, 1.07 to 1.41; P=0.0031) and placebo (RR, 1,40; 95% CI, 1.19 to 1.65; P<0.0001). In compatibility to overall treatment discontinuation, Ticagrelor was associated with increased risk for treatment discontinuation due to side effects compared to Clopidogrel (RR, 1.80; 95% CI, 1.36 to 2.38; P<0.0001), Prasugrel (RR, 1.49; 95% CI, 1.06 to 2.10; P=0.0216) and placebo (RR, 1.85; 95% CI, 1.21 to 2.83; P=0.0044). Ticagrelor, Prasugrel and Clopidogrel were associated with an increased risk for dyspnea in comparison to placebo (RR, 2.86; 95% CI, 2.57 to 3.17; P<0.0001; RR, 1.61; 95% CI, 1.35 to 1.91; P<0.0001; RR, 1.60; 95% CI, 1.41 to 1.82; P<0.0001) respectively. Ticagrelor was associated with increased risk for dyspnea compared to Clopidogrel (RR, 1.78; 95% CI, 1.65 to 1.92; P<0.0001) and prasugrel (RR, 1.78; 95% CI, 1.55 to 2.05; P<0.0001). Conclusions The findings of this study suggest that Ticagrelor presents the highest risk for premature discontinuation compared to Clopidogrel and Prasugrel. Additionally, P2Y12 receptor inhibitors, in general, are notably associated with dyspnea, with Ticagrelor showing the highest risk. These results provide health professionals with valuable information for making treatment decisions in patients post-ACS.NMA netgraphsNMA of Overall treatment discontinuation

Transoesophageal echocardiography-guided cardioversion and thromboembolism

Abstract Background To perform electrical cardioversion of atrial fibrillation or atrial flutter with a duration of more than 48 hours, it is recommended to initiate anticoagulation therapy for at least three weeks beforehand. In cases where cardioversion is necessary earlier, it is suggested to precede the procedure with a transoesophageal echocardiography to rule out the presence of a thrombus in the left atrium (referred to as TOE-guided cardioversion). This strategy is outlined in current ESC guidelines for atrial fibrillation. However due to limited evidence, no specific level of recommendation for its use is provided. Purpose This study aimed to characterize patients treated by TOE-guided cardioversion in two hospitals and to conduct a safety analysis of the procedure. The 30-day incidence of thromboembolic events was chosen as the main safety objective, the 30-day mortality as the secondary. Method This was a retrospective, two center, cohort register study where information was obtained from patients medical records. All patients who underwent TOE-guided cardioversion between 2012-2020 in the first institute, and between 2015-2020 in the second were included. From the medical records all the patient characteristics and the clinical outcomes were identified. Result A total of 259 patients, with TOE-guided cardioversions, arrhythmia duration over 48 hours and without adequate anticoagulation therapy were included. Patient characteristics are shown in table 1. It was equal incidence of a 30-day thromboembolic event (n=6) and the 30-day mortality (n=6), 2,3% respectively. Three of the six patients died of non-cardiovascular cause. One of the 30-day thromboembolic event resulted in mortality at day 31. Table 2 summarize the data related to the thromboembolic events. There was no statistically significant predictor of any of the two endpoints when comparing the patients with event and patients without. Conclusion This study shows that the risk of thromboembolic events after TOE-guided cardioversion is not negligible, 2,3% within a 30-day follow up. The 30-day mortality was 2,3%, half of which were non-cardiovascular. To analyse potential clinical predictors for any events, larger studies specifically powered for such a question is needed.

Predictors of Ischemic Stroke in a cohort of patients with Chagas Cardiomyopathy: the CLOT-Chagas study

Abstract Introduction a high risk of embolic events characterizes Chronic Chagas Cardiomyopathy (CCC) due to the presence of structural alterations of the left ventricle, the high incidence of arrhythmias, and intrinsic coagulation disorders. Despite its relevance, there is limited information on factors associated with this type of embolic event in patients with CCC, with most studies designed as case-control studies. This study aimed to prospectively analyze independently associated factors with this population's Ischemic Stroke (IS). Materials and Methods A prospective study was conducted between 2019 and 2023 at a cardiovascular center's Heart Failure and Heart Transplant Clinic. Adult patients diagnosed with CCC were included, recording sociodemographic, clinical, and echocardiographic variables as potential predictors of IS. Patients were followed up for 18 months via telephone for outcome assessment. Multivariate logistic regression models were used to identify factors potentially associated with IS during follow-up. Results A total of 232 patients diagnosed with CCC were included (males: 54.9%; median age: 67 years), the majority of whom were receiving anticoagulant therapy (n=144; 62.1%), with DOACs being the most frequently prescribed type of anticoagulants (51%). During follow-up, 16 patients (6.9%) developed an IS. There was a trend towards a lower incidence of IS in patients treated with direct oral anticoagulants (6.8%) compared to those receiving Warfarin (11.5%); however, this difference was not statistically significant (p=0.584). In the multivariate regression analysis including all potential predictors of IS, only the presence of a ventricular aneurysm (RR 5.64; 95% CI 1.61-19.70, p=0.007) and the score obtained when applying the Pfeiffer cognitive impairment questionnaire (RR 0.56; 95% CI 0.42-0.75, p<0.001) were significantly associated with the outcome of IS, even after adjusting for age, sex, NYHA functional class, ejection fraction, and anticoagulant therapy. The model composed of ventricular aneurysms and the Pfeiffer questionnaire score showed adequate performance in predicting IS during follow-up (AUC 0.79). Conclusions and Discussion: The incidence of IS in this population was higher than reported in the literature for both CCC patients and those with heart failure from other etiologies. The finding of an association between the presence of ventricular aneurysms and IS has been previously reported; however, the association between the Pfeiffer cognitive test and the development of IS represents a novel observation that deserves validation in future studies for its applicability in the clinical setting.

Association between preprocedural thromboembolic or bleeding events under oral anticoagulation therapy and mid-term outcomes after percutaneous left atrial appendage closure

Abstract Background Currently, no consensus has been established on the most effective antithrombotic therapy to prevent thromboembolic and bleeding events in patients undergoing percutaneous left atrial appendage closure (LAAC). Methods We retrospectively investigated the incidence of device-related thrombosis (DRT), thromboembolic events, and bleeding events in patients who underwent LAAC from September 2019 to October 2022. After categorizing patients into groups based on preprocedural thromboembolic or bleeding events under oral anticoagulation (OAC) therapy, we compared the incidence of DRT and prognosis according to the postprocedural antithrombotic therapy. Results In patients who received the conventional antithrombotic therapy (OAC with and without single antiplatelet therapy for 45 days after LAAC and dual-antiplatelet therapy from 45 days to 6 months followed by single antiplatelet therapy), preprocedural thromboembolic events despite OAC were independently associated with DRT or postprocedural thromboembolic events at the 3-year follow-up (hazard ratio [HR] 4.55; 95% confidence interval [CI] 1.32–15.6; P = 0.016), whereas preprocedural bleeding events were independently associated with postprocedural bleeding events (HR 8.01, 95% CI 1.45–58.3; P = 0.036). Continuation of OAC for 12 months among patients who developed preprocedural thromboembolic events during OAC significantly decreased the incidence of DRT or postoperative thromboembolic events (P = 0.002) with no increase in the bleeding events (P = 0.522). Conclusions Preprocedural thromboembolic and bleeding events can predict adverse events after LAAC with conventional antiplatelet-based antithrombotic therapy. Patients who develop thromboembolic events under continuous OAC may benefit from continuous OAC for 1 year after LAAC.