Rate Of Hemorrhagic Events Research Articles

Direct Oral Anticoagulants versus Vitamin K Antagonists for Left Ventricular Thrombus: A Meta-Analysis with Trial Sequential Analysis.

Vitamin K antagonists (VKAs) are the recommended first-line treatment for left ventricular thrombus (LVT); however, direct oral anticoagulants (DOACs) have been considered an alternative therapy. To evaluate the efficacy and safety of DOACs compared with VKAs therapy in patients with LVT. PubMed, Embase, and Cochrane were systematically searched for randomized clinical trials or cohort studies that compared DOACs versus VKAs for LVT. Risk ratios (RRs) were computed for binary endpoints, with 95% confidence intervals (95% CIs). Statistical significance was defined as p value < 0.05. A total of 4 randomized clinical trials and 29 cohort studies were included, with 4,450 patients assigned to either DOACs or VKAs. There was no significant difference between groups for stroke or systemic embolic (SSE) events (RR 0.84; 95% CI 0.65 to 1.07; p = 0.157), stroke (RR 0.73; 95% CI 0.48 to 1.11; p = 0.140), systemic embolic (SE) events (RR 0.69; 95% CI 0.40 to 1.17; p = 0.166), thrombus resolution (RR 1.05; 95% CI 0.99 to 1.11; p = 0.077), any bleeding (RR 0.78; 95% CI 0.60 to 1.00; p = 0.054), clinically relevant bleeding (RR 0.69; 95% CI 0.46 to 1.03; p = 0.066), minor bleeding (RR 0.73; 95% CI 0.43 to 1.23; p = 0.234), major bleeding (RR 0.87; 95% CI 0.42 to 1.80; p = 0.705), and all-cause mortality (RR 1.05; 95% CI 0.79 to 1.39; p = 0.752). Compared with VKAs, rivaroxaban significantly reduced SSE events (RR 0.35; 95% CI 0.16 to 0.91; p = 0.029) and SE events (RR 0.39; 95% CI 0.16 to 0.95; p = 0.037). DOACs had a similar rate of thromboembolic and hemorrhagic events, as well as thrombus resolution, compared to VKAs in the treatment of LVTs. Rivaroxaban therapy had a significant reduction in thromboembolic events, compared to VKAs.

Bleeding and thrombotic events and intensity of heparin therapy in the two first waves of COVID-19.

A systemic inflammatory response occurs during SARS-CoV2 infection and is associated with hypercoagulability and thrombotic events. From March 2020 in our hospital different dosages of low-molecular weight heparin (LMWH) were introduced according to the level of patient care intensity. Because bleeding episodes occurred in hospitalized COVID-19 patients on heparin, the dosage of LMWH at the end of first wave was tailored on the severity of COVID-19. The aim of this study is to describe bleeding and thrombotic events in patients hospitalized with SARS-CoV2 infection on LMWH therapy in the two waves of COVID-19 and analyze the factors associated with these events. Among 1143 patients enrolled in the COVID-19 Network registry, 912 were included in the analysis, 537 of them admitted during the first wave and 375 during the second. Bleeding events were 30 (3.3%): 22 (2.4%) major and 8 (0.9%) non-major. Arterial and venous thrombotic events were 6 (0.7%) and 24 (2.6%). The incidence of venous thrombotic events was higher in the first than in the second wave (0.29% [95% CI 0.20-0.45] events/day vs. 0.05% [95% CI 0.02-0.16]), with a 71% risk reduction (95% CI 22%-94%). The incidence of bleeding was 0.33% (95% CI 0.22-0.50) vs 0.14% events/day (95% CI 0.07-0.28), with no statistical between-wave difference (HR 0.41 95% CI 0.16-1.08). After adjusting for the competing risks of death and comorbidities, patients in the second wave had lower odds to have thrombotic events than in the first wave (0.24 HR [95% C.I. 0.07-0.89]). In this retrospective study on COVID-19 we found a low rate of hemorrhagic and thrombotic events, that may be explained by the absence in the case material of patients admitted to intensive care unit.

Characteristics, management and prognosis of patients with coronary artery disease undergoing coronary intervention and atrial fibrillation

Abstract Funding Acknowledgements None. Introduction The selection of antithrombotic treatment in patients with ischaemic heart disease (IHD) and atrial fibrillation (AF) represents a challenge when trying to balance ischaemic and haemorrhagic risk. However, there is little "real-life" data on the selected antithrombotic treatment and its short and long-term prognosis. Methods A Prospective multicentre study that includes patients with IHD [acute coronary syndrome (ACS) or chronic coronary syndrome (CCS)] and AF admitted to 13 Spanish centres. The objective is to describe the characteristics, antithrombotic treatment and prognosis of patients undergoing PCI and AF. Results 373 patients were included. The average age was 77.6 ± 9.8 years (28% women). Patients had a high ischaemic and haemorrhagic risk [CHA2DS2VASc 4 (2-5) and HASBLED 3 (2-4)], with 25.5% being frail according to the Clinical Frailty Scale. The main reason for admission was ACS (44.8% NSTEMI, 22.2% STEMI and 33% CCS ), and 49.8% of patients had multivessel disease. 70.3% of patients underwent revascularisation, mainly percutaneously (92.2%). Among those percutaneously revascularised, the most used antithrombotic treatment was triple therapy with double antiplatelet therapy (DAPT) + oral anticoagulant (OAC) (62.5%), followed by double therapy with monoantiplatelet therapy + OAC (29.2%). In revascularised patients over 80, the most selected antithrombotic therapy was similar: 60.5% and 28.9%, respectively. The most used OAC was apixaban (42.3%), followed by vitamin K antagonists (17.3%). One-year survival was 88.5%. 2.6% of patients presented an ischemic stroke, and 4.8% suffered a new ACS. At the same time, haemorrhagic events (BARC ≥2) were 8.9%. Conclusions A high ischaemic and haemorrhagic risk co-exists in patients with IHD and AF. In our setting, triple therapy, mainly with the use of DOACs over VKA, is the preferred therapy. The long-term mortality of this subgroup of patients with IHD is high (&amp;gt;10%), with a rate of haemorrhagic events (8.9%) higher than ischaemic events (4.8%).Characteristics of patients

Anticoagulantes Orais Diretos versus Antagonistas da Vitamina K para Trombo Ventricular Esquerdo: Uma Metanálise com Análise Sequencial de Ensaios

Abstract Background Vitamin K antagonists (VKAs) are the recommended first-line treatment for left ventricular thrombus (LVT); however, direct oral anticoagulants (DOACs) have been considered an alternative therapy. Objectives To evaluate the efficacy and safety of DOACs compared with VKAs therapy in patients with LVT. Methods PubMed, Embase, and Cochrane were systematically searched for randomized clinical trials or cohort studies that compared DOACs versus VKAs for LVT. Risk ratios (RRs) were computed for binary endpoints, with 95% confidence intervals (95% CIs). Statistical significance was defined as p value &lt; 0.05. Results A total of 4 randomized clinical trials and 29 cohort studies were included, with 4,450 patients assigned to either DOACs or VKAs. There was no significant difference between groups for stroke or systemic embolic (SSE) events (RR 0.84; 95% CI 0.65 to 1.07; p = 0.157), stroke (RR 0.73; 95% CI 0.48 to 1.11; p = 0.140), systemic embolic (SE) events (RR 0.69; 95% CI 0.40 to 1.17; p = 0.166), thrombus resolution (RR 1.05; 95% CI 0.99 to 1.11; p = 0.077), any bleeding (RR 0.78; 95% CI 0.60 to 1.00; p = 0.054), clinically relevant bleeding (RR 0.69; 95% CI 0.46 to 1.03; p = 0.066), minor bleeding (RR 0.73; 95% CI 0.43 to 1.23; p = 0.234), major bleeding (RR 0.87; 95% CI 0.42 to 1.80; p = 0.705), and all-cause mortality (RR 1.05; 95% CI 0.79 to 1.39; p = 0.752). Compared with VKAs, rivaroxaban significantly reduced SSE events (RR 0.35; 95% CI 0.16 to 0.91; p = 0.029) and SE events (RR 0.39; 95% CI 0.16 to 0.95; p = 0.037). Conclusions DOACs had a similar rate of thromboembolic and hemorrhagic events, as well as thrombus resolution, compared to VKAs in the treatment of LVTs. Rivaroxaban therapy had a significant reduction in thromboembolic events, compared to VKAs.

Ibrutinib As First Line Therapy in Chronic Lymphocytic Leukemia Patients over 80 Years Old: A Retrospective Real-Life Multicenter Italian Cohort

Background: Although CLL primarily affects older adults (median age 71 years), limited data exist about the outcomes of adults who are ≥80 years old because they are under-enrolled in clinical trials. Methods: We performed a multicenter national study enrolling consecutive treatment-naïve CLL patients ≥80 years at the time of frontline CLL therapy, treated with ibrutinib. Kaplan-Meier analyses were used to plot progression-free survival (PFS) and overall survival (OS). Results: Our study included 79 patients with CLL who were aged ≥80 years at the time of frontline CLL therapy starting between 1/2014 and 3/2021; the clinical features of these patients are summarized in Table 1. A total of 13 (16.5%) patients achieved a nodal clinical response (CR; bone marrow evaluation was not performed), 58 (73.4%) a partial response (PR) or PR + lymphocytosis (PR+L), 3 (3.8%) a stable disease (SD), and 5 (6.3%) were not evaluated since they early withdrew ibrutinib. Discontinuation because of progressive disease (PD) occurred in 9 cases (11%), whereas discontinuation due to toxicity in 11 patients (13.9%). The most common grade &amp;gt;3 adverse events (AEs) were infections (25.5%), neutropenia (10.1%), and anemia (2.5%). Eighteen patients (22.8%) experienced cardiovascular events: 9 (11%) had atrial fibrillation (AF), 5 hypertension (6%), 3 heart failure (3%), and 1 acute coronary syndrome (1%). All cases of AF and hypertension were of grade 2. Patients with AF received anticoagulation and no thrombotic stroke were recorded. Bleeding events were observed in 27 (34.2%) patients but were mild, of grade 1-2 in 24 and grade 3 in 3. Patients who received anticoagulants or anti-platelets drugs did not experienced a significantly higher rate of hemorrhagic events than those not assuming anticoagulation. Secondary malignancies were reported in 6 patients (7.8%) and Richter's transformation in five. Temporary drug withdrawal (7-30 days) occurred in 33 patients (41.8%): in 17 (21.5%) due to infections, 5 (6.3%) cardiovascular events, 10 (12.7%) hemorrhagic events, and 4 (5.1%) hematologic toxicity. Ibrutinib was permanently discontinued in 26 patients (32%): in 9 with PD (Richter's syndrome, 5), 6 with secondary malignancies, 5 with infections, 3 with cardiac failure, 2 due to severe bleeding and a sudden death was reported in 1. After a median follow-up of 24 months, the median PFS was 49.3 months (95% CI 39.9-58.7) and the median OS 51.8 (95% CI 50.1-53.5). Age, sex, creatinine clearance, Binet stage, del17p, TP53 and IGHV mutational status did not significantly impact PFS. Conversely, CIRS &amp;gt;6 was associated with a significantly shorter PFS (median PFS: 33.1 months, 95% CI 25.3-40.9 vs. not reached, p=0.016). A significantly longer PFS (p=0.03) was observed in the 46 patients who never discontinued ibrutinib or stopped the drug for less than 7 days (median PFS 66.3 months, 95% CI 50.5-82.1) compared to those with a transient treatment discontinuation, between 7 and 30 days, (median PFS; 32.7 months, 95% CI 23.2-42.3) (Figure 1). Sex, creatinine clearance, Binet stage, IGHV, del17p, and TP53 mutational status, as well as CIRS, did not significantly impact OS. Conversely, a trend toward a statistically significant longer OS (P=0.07) was observed for patients who discontinued ibrutinib &amp;lt;7 days (67.2 months, 95% CI 43.5-90.9) compared with those who discontinued for 7-30 days (51.8 months, 95% CI 34.4-69.2). Conclusions: To our knowledge, this is the largest real-world study examining treatment-naive elderly patients receiving ibrutinib as first-line therapy. Ibrutinib represents a suitable therapeutic choice even for patients aged &amp;gt;80 years with comorbidities. In this setting of patients, the drug was well tolerated and no new side effects were recorded.

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.

Platelet Response in Pacritinib-Treated Patients with Cytopenic Myelofibrosis: A Retrospective Analysis of PERSIST-2 and PAC203 Studies

Background: Myelofibrosis (MF) is a myeloid malignancy characterized by clonal hematopoisis, bone marrow fibrosis (BMF) and ineffective extramedullary hematopoiesis, resulting in progressive cytopenias. Thrombocytopenia is both prognostic of poor outcomes and predictive of treatment intolerance with the JAK1/2 inhibitor ruxolitinib, which exacerbates cytopenias. Pacritinib is a JAK1-sparing inhibitor of JAK2/IRAK1/ACVR1 that can be administered at full dose to patients regardless of baseline platelet count (PLT). While prior studies have shown that pacritinib is associated with PLT stability in most patients, PLT improvement has not been described outside of a recently published case report ( Yacoub A, et al. JCO Precis Oncol. 2023;7:e2200523). Here, we report rates of hematologic improvement in PLTs (HI-P) with pacritinib across two clinical trials. Methods: Patients with baseline PLT ≤100x10 9/L on the pacritinib 200 mg BID arms of the phase 3 PERSIST-2 study (randomized ≥12 weeks prior to study termination) or the phase 2 dose-finding PAC203 study were included. HI-P was defined per International Working Group (IWG) criteria (baseline PLT &amp;lt;20x10 9/L: increase to &amp;gt;20x10 9/L and by at least 100%; baseline PLT 20-100 x 10 9/L: absolute increase of ≥30x10 9/L) in the absence of PLT transfusions, sustained over any 8 weeks while on treatment. Efficacy outcomes (reduction in spleen volume, symptom score, and BMF) were compared between HI-P responders vs non-responders (those who did not meet IWG criteria). Rates of PLT improvement were also analyzed on the best available therapy (BAT) arm of the PERSIST-2 study over the treatment period (end of study treatment). Results: Of 117 patients randomized to pacritinib (75 from PERSIST-2, 42 from PAC203), 16% (n=19) experienced HI-P on study (as defined in methods). Additionally, 14 of the 19 HI-P patients had sustained platelet improvement over ≥12 weeks). By contrast, only 5% (4/77) of patients on BAT achieved HI-P response prior to end of study treatment. HI-P responders on pacritinib compared to non-responders, had numerically higher median baseline PLT count (63 vs 45x10 9/L) and hemoglobin (Hb; 10.3 vs 8.8 g/dL). A similar percentage had prior (&amp;lt;30 days) JAK2 inhibitor exposure (68.4% vs 66.3%) and JAK2V617F mutation (78.9 vs 74.5%); median JAK2 allele burden was low in both responders and non-responders (26.7% vs 36.9%). Among HI-P responders with prior ruxolitinib exposure, most (85%, 11/13) had recent exposure within the prior 30 days, with median dose of 10 mg BID. PLT improvement was noted within the first 12 weeks in most HI-P responders, whereas PLT count remained stable, on average, among non-responders ( Figure 1a). To evaluate if recent ruxolitinib exposure and washout of drug was responsible for HI-P, we analyzed the subset of patients with ruxolitinib exposure in previous 30 days (11/19). The mean platelet count increased from 56 to 141x10 9/L at week 12. In the remaining 8/19 patients without recent ruxolitinib exposure (n=6 were treatment naïve), platelets increased from 59 to 102 x 10 9/L at week 12. While there was no difference in the magnitude of spleen volume or symptom score reduction in HI-P responders vs non-responders, a correlation with change in BMF was noted. Among the 36 patients with available bone marrow data from baseline and week 24, HI-P responders were numerically more likely to have BMF reduction (67%, n=4/6) compared to non-responders (23%, n=7/30, P=0.057, Figure 1b). There was no difference in the rate of hemorrhagic events (by standardized MedDRA queries) in PLT responders vs non-responders (47% vs 46%), though grade ≥3 bleeding was observed at lower frequency in responders compared to non-responders (10.5% vs 16%). Other commonly reported adverse events with pacritinib occurred at similar frequency between responders and non-responders. Discussion: PLT improvement meeting IWG criteria occurs in a subset of MF patients treated with pacritinib and does not seem to be explained by changes in spleen volume. Further studies are warranted to assess the correlation between hematologic improvement and BMF reduction with pacritinib. It is possible that pacritinib's unique mechanism of action as an IRAK1 inhibitor could result in modulation of the bone marrow microenvironment and thrombopoiesis. Study funded by CTI BioPharma Corp., a Sobi company.

Predictors of ischemic and hemorrhagic complications in patients with myocardial infarction at 18-month follow-up: a single-center registry study

Aim. To identify predictors of ischemic and hemorrhagic events in patients with myocardial infarction (MI) after 18 months of follow-up.Material and Methods. The single-center prospective study included 478 patients with MI. The exclusion criteria were as follows: age &lt; 18 years; MI as a complication of myocardial revascularization; atrial fibrillation; intake of anticoagulants after MI. During inpatient treatment, the risk of ischemic and hemorrhagic events was calculated according to the PRECISE-DAPT score, GRACE hospital discharge risk score, CRUSADE bleeding score. After 18 months, we evaluated the rate of ischemic (cardiovascular death, unstable angina, life-threatening arrhythmia, non-fatal MI and stroke, acute decompensated heart failure, elective repeated and/ or emergency revascularization) and haemorrhagic events and the amount of corresponding therapy.Results. At 18 months post-MI, patients were at high risk of developing both ischemic events (cardiovascular death: 32.0%; recurrent MI: 16.3%; repeated myocardial revascularization: 18.5%; unstable angina: 13.8%; stroke: 3.6%) and hemorrhagic events (bleeding rate of 39.7% according to the TIMI score), most of which occurred during the first 12 months post-MI. Double antiplatelet therapy (DAPT) was prescribed to 86.5% patients upon discharge (including a triple antithrombotic therapy in 8.6% patients). Patient adherence to treatment was 66.7% and 60.6% at 6 and 12 months of follow-up, respectively. After 18 months, DAPT was prescribed exclusively to patients suffered from recurrent ischemic events or those who underwent repeated myocardial revascularization (17.4% patients in total). The main reason to cancel DAPT was bleeding, although it was minor in most cases. Predictors of ischemic events (fatal and non-fatal) at 18 months of follow-up were PRECISE- DAPT score (odds ratio (OR) = 1.108, 95% confidence interval (CI) = 1.054-1.164, р &lt; 0.001), GRACE score (OR = 1.032, 95% CI = 1.016-1.048, р &lt; 0.001), left ventricular ejection fraction (LVEF) &lt; 40% (OR = 4.256, 95% CI = 1.510-12.001, р = 0.006). Predictors of hemorrhagic events at 18-month follow-up were PRECISE-DAPT score (OR = 1.025, 95% CI = 1.009-1.041, р = 0.002), peripheral artery disease (PAD) (OR = 2.459, 95% CI = 1.365-4.428, р = 0.003), intake of sulfonylurea for diabetes mellitus (OR = 2.523, 95% CI = 1.266-5.028; р = 0.009), unsuccessful percutaneous coronary intervention (PCI) or conservative treatment of MI (OR = 3.792, 95% CI = 1.799-7.996, р &lt; 0.001).Conclusion. Predictors of ischemic events (fatal and non-fatal) in the long-term period after MI include PRECISE-DAPT and GRACE scores, and LVEF below 40%. Predictors of hemorrhagic events at 18-month follow-up were PRECISE- DAPT scores, PAD, taking sulfonylurea for diabetes mellitus, unsuccessful PCI or conservative treatment of MI.

Safety and efficacy of the p48 MW and p64 flow modulation devices: a systematic review and meta-analysis.

Flow diverters (FDs) have demonstrated increasing safety and efficacy in treating various types of intracranial aneurysms. Although the underlying mechanism of action of all FDs is similar, differences are noted in their intrinsic characteristics, materials, and deployment techniques. The p64 flow modulation device (p64) and the newer p48 movable wire flow modulation device (p48 MW) are not yet available in the US but have been increasingly used mainly in Europe, demonstrating optimistic results. The authors performed a systematic review and meta-analysis of the literature to evaluate the safety and efficacy of the p64 and p48 MW FDs. A literature review (between January 1960 and November 2022) of the PubMed, Scopus, Embase, Web of Science, and Cochrane Central Register of Controlled Trials databases was conducted. The primary efficacy outcome was the proportion of complete angiographic occlusion at last follow-up. Complete occlusion was defined as Raymond-Roy class 1 and O'Kelly-Marotta grade D. The primary safety outcomes were the composite safety rate of ischemic and hemorrhagic events (intra- and postprocedure) and the all-cause mortality rate. Data were analyzed using a random-effects proportions meta-analysis, and statistical heterogeneity was assessed. Twenty studies with 1781 patients harboring 1957 aneurysms were included in the analysis. Seventeen studies were conducted in Europe. Sixteen studies evaluated the performance of the p64 (MW). Patient ages ranged between 20 and 89 years, and most were female (78.7%). Aneurysm size ranged between 1 and 50 mm. Most aneurysms were unruptured (92.8%) and in the anterior circulation (93.1%). Single antiplatelet therapy pre- and postprocedure was used in 2 studies. Follow-up ranged from 2 to 14.5 months. For the p64 and p48 MW, complete angiographic occlusion rates were 77% (95% CI 68%-85%) and 67% (95% CI 49%-81%), adjunctive coil usage rates were 7% (95% CI 4%-12%) and 4% (95% CI 0%-24%), primary safety composite rates were 2% (95% CI 1%-4%) and 3% (95% CI 1%-11%), and mortality rates were 0.49% (95% CI 0%-1%) and 2% (95% CI 1%-6%), respectively. The p64 and p48 MW have primarily been used in Europe thus far. This analysis found that both devices have an acceptable efficacy and favorable safety profile. However, further studies are needed to evaluate the efficacy and safety of prescribing a single antiplatelet regimen after implantation of the newer-generation FDs with antithrombotic coating surface modification.

ACOD en pacientes con fibrilación auricular e intervención quirúrgica sobre la válvula mitral

Introduction and objectivesAlthough the usage of direct oral anticoagulants (DOAC) in patients with atrial fibrillation (AF) and intervention on the mitral valve (biological valve prosthesis or repair) is included in the clinical practice guidelines as an alternative to vitaminK antagonists (VKA), real world data in this scenario remain scarce. MethodsOur study included all patients who underwent mitral valve replacement by biological prosthesis or mitral valve repair in our hospital between 2014 and 2020, with indication of anticoagulation due to AF. We compared rates of cerebrovascular events, major and minor bleeding, and mortality, between those treated with DOACs and VKAs. ResultsWe selected 105 patients: 75 submitted to biological replacement and 30 to repair. After a mean follow-up of 2.8years, 41 patients were treated exclusively with VKA, and 64 started DOACs —34 as anticoagulant from the beginning, and 30 after switching from VKA. There were no significant differences in their baseline clinical characteristics in terms of age, sex, kidney function, or embolic or bleeding risk scales between groups. There were no differences in the rate of stroke and major bleeding between patients with VKA or DOAC (major bleeding, VKA n=6, 8.4% vs DOAC n=4, 11.7%; stroke/TIA, VKA n=5, 7.04% vs DOAC 2, 5.8%), with 2 intracranial hemorrhages under VKA (2.8%). ConclusionsThe use of DOACs in a real-life cohort of patients with mitral valve surgery (biological prosthesis or repair) is an effective and safe alternative to the use of VKAs, without differences in the rate of ischemic or hemorrhagic events.

Oral anticoagulants (NOAC and VKA) in chronic thromboembolic pulmonary hypertension.

EXPERT was an international, multicenter, prospective, uncontrolled, non-interventional cohort study in patients with pulmonary hypertension treated with riociguat. Patients were followed for 1-4 years, and the primary outcomes were adverse events (AEs) and serious AEs (SAEs), including embolic/thrombotic and hemorrhagic events. Here we report data on patients with chronic thromboembolic pulmonary hypertension (CTEPH) receiving a vitamin K antagonist (VKA; n=683) or a non-vitamin K antagonist oral anticoagulant (NOAC; n=198) at baseline. AEs and SAEs were reported in 438 patients (64.1%) and 257 patients (37.6%), respectively, in the VKA group, and in 135 patients (68.2%) and 74 patients (37.4%) in the NOAC group. Exposure-adjusted hemorrhagic event rates were similar in the two groups, while exposure-adjusted embolic and/or thrombotic event rates were higher in the NOAC group, although the numbers of events were small. Further studies are required to determine the long-term effects of anticoagulation strategies in CTEPH.

Eficacia de la tromboprofilaxis con heparina de bajo peso molecular en pacientes críticos con COVID-19: estudio observacional, prospectivo y multicéntrico

IntroductionCOVID-19 induces coagulopathy associated with an increase of thromboembolic events. Due to the lack of agreement on recommendations for thromboprophylactic management, the aim of this study was to study the dosages of LMWH used in critically ill COVID-19 patients assessing the effect on their outcome. MetohdsWe evaluated data of the Reg-COVID19. According to LMWH dose two groups were analyzed: prophylaxis and treatment. Primary outcome was the relationship of LMWH dosage with mortality. Secondary outcomes included the incidence of thrombotic and bleeding events, length of ICU stay, invasive mechanical ventilation, and thrombotic and inflammatory parameters. ResultsData of 720 patients were analyzed, 258 in the prophylaxis group and 462 in the treatment group. C Reactive Protein, invasive mechanical ventilation, tocilizumab and corticosteroid treatments were related with the choice of LMWH dose. Hemorrhagic events (66/720, 9.2%) and thrombotic complications (69/720, 9.6%) were similar in both groups (P=.819 and P=.265), as was the time course of the thrombotic events, earlier than hemorrhagic ones (9 [3-18] and 12 [6-19] days respectively). Mortality was lower in prophylaxis group (25.2% versus 35.1%), but once an inverse probability weighting model was applied, we found no effect of LMWH dose. ConclusionWe found no benefit or harm with the administration of therapeutic or prophylactic LMWH dose in COVID19 critically ill patients. With a similar rate of hemorrhagic or thrombotic events, the LMWH dose had no influence on mortality. More studies are needed to determine the optimal thromboprophylaxis protocol for critically ill patients.

Antithrombotic Therapy for Patients With Atrial Fibrillation and Bioprosthetic Valves - Real-World Data From the Multicenter, Prospective, Observational BPV-AF Registry.

Although bioprosthetic valve (BPV) replacements are becoming more common within our aging society, there are limited prospective data on the appropriate antithrombotic therapy for East Asian patients with atrial fibrillation (AF) and BPV replacement. Antithrombotic therapy and thrombotic and hemorrhagic event rates in Japanese patients with AF and BPV replacement are investigated.Methods and Results:This multicenter, prospective, observational study enrolled patients with BPV replacement and AF. The primary efficacy outcome was stroke or systemic embolism, and the primary safety outcome was major bleeding. Of the 894 patients analyzed, 54.7%, 29.4%, and 9.6%, were treated with warfarin-based therapy, direct oral anticoagulant (DOAC)-based therapy, or antiplatelet therapy without anticoagulants, respectively; 6.3% did not receive any antithrombotic drugs. The mean observation period was 15.3±4.0 months. The event rates for stroke or systemic embolism and major bleeding were 1.95%/year and 1.86%/year, respectively. The multivariate adjusted hazard ratios for DOAC vs. warfarin were 1.02 (95% confidence intervals [CI], 0.30-3.41 [P=0.979]) for systemic embolic events and 0.96 (95% CI, 0.29-3.16 [P=0.945]) for major bleeding. Approximately 30% of patients with AF and BPV replacement were treated with DOAC. The risks of major bleeding and stroke or systemic embolism were similar between warfarin- and DOAC-treated patients with AF who had BPV replacement. Treatment with DOACs could be an alternative to warfarin in this population.

The safety and efficacy of a low dose of tirofiban for early complications during and after stent-assisted coiling of ruptured intracranial aneurysms: A propensity matching study

PurposeDuring stent-assisted coiling of ruptured intracranial aneurysms (RIA), appropriate antiplatelet administration is an important element of management. We aimed to evaluate the safety and efficacy of intravenous tirofiban administration versus dual antiplatelet therapy (DAPT) for stent-assisted coiling of RIAs within 24 h after procedure. MethodsFrom January 2015 to March 2019, two groups of patients with RIAs treated with stent-coiling were compared: the DAPT group (a loading dose of 300 mg clopidogrel and 300 mg aspirin) and the tirofiban group (intravenous administration of tirofiban 5 µg/kg over 1 min, followed by a maintenance dose of 0.1 µg/kg/min). The main outcome measures were rates of ischemic events and intracranial hemorrhage. Propensity score-matching (PSM) analysis was performed to correct imbalances in patient characteristics between the two groups. ResultsA total of 200 patients with RIAs were identified, with 36 patients in DAPT group and 164 in tirofiban group. After PSM, 36 patients in DAPT group and 72 patients in tirofiban group were matched. Ischemic events were noted for 8.33% (3/36) of patients in DAPT group, and 4.17% (3/72) in tirofiban group within 24 h after procedure(P = 0.398). Intracranial hemorrhage was noted for 0.00% (0/36) of patients in DAPT group, and 1.39% (1/72) in tirofiban group (P = 1.000) within 24 h. And no significant difference in the rate of ischemic or hemorrhagic events after 24 h was detected. ConclusionsIntravenous administration of a low dose of tirofiban may represent a safe and effective alternative to DAPT during stent-assisted coiling of RIAs.

Evaluation of Bivalirudin-Associated Major Adverse Cardiac and Hemorrhagic Events in Acute Coronary Syndrome Patients on Chronic Dialysis Following Percutaneous Coronary Intervention.

Patients with chronic dialysis dependency undergoing percutaneous coronary intervention (PCI) are at a greater risk of hemorrhagic and ischemic events. Due to their exclusion from randomized clinical trials, the optimal antithrombotic regimen for this population remains unknown. Bivalirudin has been associated with fewer hemorrhagic complications than unfractionated heparin (UFH) in patients undergoing PCI. We evaluated major adverse cardiac event (MACE) and hemorrhagic event rates for an antithrombotic regimen using bivalirudin or UFH during PCI in acute coronary syndrome (ACS) patients with chronic dialysis dependency. A retrospective study was performed, including 211 patients on dialysis undergoing PCI due to ACS from January 2014 to April 2019 at the China-Japan Friendship Hospital. Patients were divided into 2 groups based on anticoagulation regimen: the bivalirudin group (86 cases) or the UFH group (125 cases) during and after PCI. Statistical analyses were used to compare MACE and hemorrhagic events between groups at 30 days after PCI. No patients experienced stent thrombosis within 30 days after PCI regardless of anticoagulant. There was no difference in the incidence of MACE in the bivalirudin group compared with the UFH group (6.98% vs 8.80%, respectively; P>.05). The rate of hemorrhagic events in the bivalirudin group was significantly lower than in the UHP group (5.81% vs 18.4%, respectively; P<.05), particularly for rates of mild bleeding (4.65% vs 15.2%, respectively; P<.05). There were no significant differences in rates of severe bleeding between the bivalirudin and UFH groups (1.16% vs 4.00%, respectively; P>.05), although fewer severe hemorrhagic events occurred in the bivalirudin group. Bivalirudin was associated with fewer bleeding events following PCI in individuals with end-stage renal disease on dialysis.

Hemorrhagic Events in Patients Receiving Heparin or Enoxaparin in Combination With Oral Antithrombotics, NSAIDs, and Antiplatelet Medications: A Multi-Center Case-Series Study

Background: Hemorrhagic events are amongst the significant adverse effects of injectable anticoagulants such as heparin and enoxaparin. This undesirable effect needs close monitoring of their use for clinically relevant drug-drug interactions.&#x0D; Objectives: To study the rate of hemorrhagic events, the anatomical site, and the severity of the bleeding in patients receiving heparin or enoxaparin in combination with clopidogrel, Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), and warfarin.&#x0D; Methods: We designed a prospective, multi-center, case-series study. Patients admitted to two teaching hospitals who received either an NSAID, or warfarin, or clopidogrel were evaluated. Any hemorrhagic event was recorded by Yellow Card Scheme. Also, the Naranjo scale was utilized for causality assessment.Results: A total of 123 patients were eligible for inclusion. They were admitted between November 2014 and April 2015. Sixty-five patients (52.5%) received heparin and 58 patients (47.2%) received enoxaparin. Of 123 patients, 115 patients (93.5%) received aspirin, 69 (56.1%) warfarin, 34 (27.6%) an antiplatelet medication, and 121 (98.4%) NSAIDs in combination with heparin or enoxaparin. Overall, 26 cases (21.1%) of the hemorrhagic incident were reported, of whom six cases (4.9%) were categorized as major bleeding. Patients receiving heparin constituted the largest proportion among all 26 hemorrhagic incidents (57.7%). All patients with the hemorrhagic incident had aspirin in their medication regimen, while 19 patients (73.0%) were concomitantly receiving warfarin as well. Hematuria (46.2%), hematoma in the injection site (38.5%), and hematoma (34.6%) were the top three types of hemorrhagic events. In Naranjo scale analysis, 19 patients scored more than 9 points, indicating a definite Adverse Drug Reaction (ADR) causality. Moreover, seven patients scored 5 to 8, affirming a possible association with ADR.&#x0D; Conclusion: The risk of hemorrhagic can be influenced by undesirable drug-drug interactions. Close monitoring of high-risk patients is advised to prevent adverse hemorrhagic reactions. Further studies to detect the explanatory factors associated with the hemorrhagic events are recommended.&#x0D;

The Safety and Effectiveness of Bevacizumab in the Treatment of Nonsquamous Non-Small-Cell Lung Cancer: A Meta-Analysis of Randomized Controlled Trials.

Objective Bevacizumab was currently available for nonsquamous non-small-cell lung cancer (NSqNSCLC) patients and has been studied in several randomized controlled trials (RCTs) for treatment of these patients. This meta-analysis summarizes the most up-to-date evidences regarding the effects and adverse reactions of bevacizumab in the treatment of NSqNSCLC patients. Methods The authors searched for RCTs from electronic database including PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. Experimental arm was defined as the bevacizumab-containing group and the control arm as the bevacizumab-free group. Data of objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse reactions were synthetically extracted. A protocol for this meta-analysis has been registered on PROSPERO (http://www.crd.york.ac.uk/prospero). Results Ten RCTs that involved a total of 3134 patients were included. The experimental group was associated with significant superior ORR (RR 1.63, 95% CI 1.24 to 2.14, P < 0.001), OS (HR 0.90, 95% CI 0.82 to 0.99, P < 0.001), and prolonged PFS (HR 0.68, 95% CI 0.62 to 0.74, P < 0.001) compared to the control. No significant difference was observed regarding DCR (RR 1.13, 95% CI 0.99 to 1.30, P = 0.08). The experimental group showed higher rate of hypertension (RR 6.91, 95% CI 4.62 to 10.35, P < 0.00001) and hemorrhagic events (RR 3.07, 95% CI 1.78 to 5.30, P < 0.0001) than the control group. The experimental group showed lower rate of anemia (RR 0.72, 95% CI 0.55 to 0.96, P = 0.02) than the control group. No significant difference was observed regarding treatment-related adverse event grade 3-5 (TRAE3-5) (RR 1.23, 95% CI 0.99 to 1.53, P = 0.06), thrombocytopenia (RR 1.11, 95% CI 0.92 to 1.33, P = 0.29), and neutropenia (RR 1.11, 95% CI 0.88 to 1.40, P = 0.36). Conclusion This meta-analysis showed that bevacizumab could increase ORR, OS, and prolonged PFS for treatment of NSqNSCLC patients. However, no significant improvement in DCR was observed and bevacizumab could increase the rate of hypertension and hemorrhagic events. Bevacizumab was an acceptable option for NSqNSCLC patients. This trial is registered with PROSPERO registration number: CRD42021226790.

Tolerability of Molecular-targeted Agents for Hepatocellular Carcinoma Treatment in Haemophiliacs.

Hepatocellular carcinoma (HCC) is considered a leading cause of death in patients with haemophilia. Recent advances in the treatment of unresectable HCC with molecular-targeted agents (MTAs) have led to better clinical outcomes. However, the tolerability of MTAs by haemophilic patients with HCC remains unclear. This study aimed to compare the tolerability of MTAs in such patients. From January 2011 to October 2020, five haemophilic patients with HCC were treated with MTAs. Adverse events were assessed in comparison with 265 non-haemophilic patients with HCC. The prevalence of hand-foot skin reaction was not higher in the haemophiliacs than in the non-haemophiliacs, whereas the rate of haemorrhagic events was higher in the haemophiliacs (6.0% versus 40.0%, p=0.037). Haemophiliacs tolerate long-term MTA use, without the occurrence of life-threatening complications. However, careful observation and prevention are needed for MTA-related gastrointestinal bleeding in haemophiliacs.

Whether Intracranial Aneurysm Could Be Well Treated by Flow Diversion: A Comprehensive Meta-Analysis of Large-Sample Studies including Anterior and Posterior Circulation.

Background Flow diversion (FD) has become a widely adopted treatment method for intracranial aneurysms in the clinic, but a comprehensive meta-analysis of large-sample studies including anterior and posterior circulation is still lacking. Methods The PubMed, Embase, Web of Science, and Cochrane databases were searched between January 1, 2008, and December 1, 2019. A random-effect model was used to calculate the efficacy and safety data as well as 95% confidence intervals (CIs). Results The pooled sample size of all included studies was 6695 patients; the mean age was 55.5 years old, with a total of 7406 aneurysms. For efficacy, the complete occlusion rate in angiographic follow-up (AFU) at 6 months was 78% (95% CI, 0.77, 0.80), and the AFU rate at 6-12 months was 90% (95% CI, 0.88, 0.92). For safety, the hemorrhagic event rate was 2%, the ischemic event rate was 5%, and the mortality rate was 3%. Conclusion FD is an effective and safe treatment for intracranial aneurysm with high complete occlusion rate and acceptable complication rate.

Long-term cerebrovascular outcomes after bariatric surgery: A nationwide cohort study

BackgroundThe proinflammatory state and metabolic changes associated with obesity contribute to cerebrovascular disease. Bariatric surgery can achieve a reliable reduction in body weight and improved metabolic profile in obese patients. However, its impact on cerebrovascular morbidity remains unexplored. This study investigates the effect of bariatric surgery on long-term risk of major cerebrovascular events. MethodsA retrospective cohort study was designed. Data was extracted from the Clinical Practice Research Datalink. 4212 bariatric surgery patients were compared to 4212 age, sex, and BMI-matched controls. The primary composite endpoint was occurrence of any major adverse cerebrovascular event. Secondary endpoints included composite endpoints of ischaemic events, haemorrhagic events, individual components of the primary endpoint alone and all-cause mortality. An adjusted Cox proportional hazards model was implemented to analyse time to event data. ResultsMean follow-up length was 11.4 years. The primary endpoint occurred in 73 patients. The bariatric surgery group had significantly lower adjusted major cerebrovascular event rates (HR 0.352, 95 %CI 0.195−0.637). Bariatric surgery was associated with lower rates of ischaemic events (HR 0.315, 95 %CI 0.156−0.635), particularly from transient ischaemic attacks (HR 0.364, 95 %CI 0.171−0.775). There was no difference in the rate of haemorrhagic events (HR 0.442, 95 %CI 0.147−1.330) or acute ischaemic stroke (HR 0.221, 95 %CI 0.046−1.054). In total 229 patients died during follow-up. Overall, all-cause mortality was significantly lower in the bariatric surgery group (HR 0.352, 95 %CI 0.195−0.637). ConclusionsThis study identifies an association between bariatric surgery and lower long-term risk of major adverse cerebrovascular events in patients with obesity.