Risk Of Major Bleeding Research Articles

Patients with atrial fibrillation and common exclusion criteria from clinical trials are at high risk of clinical events: the Murcia AF Project II (MAFP-II) cohort study

BackgroundSome clinical characteristics and comorbidities in atrial fibrillation (AF) patients are exclusion criteria in randomized clinical trials (RCTs) investigating oral anticoagulants (OAC). However, these conditions are present also in everyday clinical practice patients. We compared the risk of adverse clinical outcomes between patients with and without RCT exclusion criteria.MethodsThe Murcia AF Project II was an observational cohort study including AF outpatients starting vitamin K antagonists (VKAs) from July 2016 to June 2018. For the selection of the exclusion criteria, the four pivotal RCTs of direct-acting OAC (DOACs) were used as reference. During 2 years, all ischemic strokes/transient ischemic attacks, major adverse cardiovascular events (MACEs), major bleeds, and all-cause deaths were recorded.Results1050 patients (51.5% female, median age 77 years) were included, of whom 368 (35%) met at least one exclusion criterion for RCTs. During follow-up, the incidence rate ratios for major bleeding, MACE and all-cause mortality were higher among patients with exclusion criteria (all p < 0.001). Patients fulfilling at least one exclusion criterion had increased risks of major bleeding (aHR 1.48; 95% CI 1.22–1.81; p < 0.001), MACE (aHR 1.51, 95% CI 1.10–2.09, p = 0.012), and mortality (aHR 3.22, 95% CI 2.32–4.48, p < 0.001), as well as a lower event-free survival (all log-rank p < 0.001).ConclusionsIn this AF cohort taking VKAs, more than one-third had at least one RCT exclusion criteria, which translates into higher risk of major bleeding, MACE, and death. These observations should be considered when translating RCTs results to AF patients for a proper and a more patient-centered management.

Different antithrombotic strategies after coronary artery bypass grafting to prevent adverse events: a retrospective analysis

ObjectiveCoronary artery bypass grafting (CABG) is associated with antithrombotic therapy in terms of postoperative adverse events; however, it is still unknown whether the early use of such drugs after CABG is safe and effective. In this study, we aim to evaluate the relationship between different postoperative antithrombotic strategies and in-hospital adverse events in patients undergoing isolated coronary artery bypass grafting surgery.MethodsThis was a single-center, retrospective cohort analysis of patients undergoing isolated CABG due to coronary artery disease (CAD) between 2001 and 2012. Data were extracted from the Medical Information Mart for Intensive Care III database. The patients involved were divided into the ASA (aspirin 81 mg per day only) or DAPT (aspirin plus clopidogrel 75 mg per day) group according to the antiplatelet strategy. Patients were also stratified into subgroups based on the type of anticoagulation. The in-hospital risk of bleeding and adverse events was investigated and compared between groups. Propensity score matching (PSM) was performed to reduce the potential effects of a selection bias.ResultsA total of 3274 patients were included in this study, with 2358 in the ASA group and 889 in the DAPT group. Following the PSM, no significant difference was seen in the risk of major bleeding between the two groups according to the PLATO, TIMI or GUSTO criteria. There was no difference in the postoperative mortality. In subgroup analysis, patients given anticoagulant therapy had an increased incidence of bleeding-related events. Multivariable analysis revealed that postoperative anticoagulant therapy and the early use of heparin, but not DAPT, were independent predictors of bleeding-related events.ConclusionsPostoperative DAPT was not associated with an increased occurrence of bleeding-related events in patients undergoing isolated CABG and appears to be a safe antiplatelet therapy. The addition of anticoagulants to antiplatelet therapy increased the risk of bleeding and should be considered cautiously in clinical practice.

Ticagrelor versus Clopidogrel in Prevention of No Reflow after 1ry PCI in Diabetic Patients with STEMI

Abstract Background Adequacy of coronary flow can be judged upon using several methods like TIMI Grade and myocardial blush grade. No-reflow phenomenon, defined as incomplete reperfusion at the microvascular level despite adequate patency of the occluded artery, remains an important limitation of primary percutaneous intervention in STEMI patients nowadays. We aim in this study to investigate the relationship between the antiplatelet loading dose whether to be Ticagrelor or Clopidogrel and post intervention coronary flow, bleeding risk in these patients. Aim of the Work To compare between the effects of preoperative loading dose of Ticagrelor and clopidogrel in Diabetic STEMI patients undergoing primary percutaneous coronary intervention regarding prevention of no reflow, Instent thrombosis and short term bleeding risk. Myocardial reperfusion was judged upon using TIMI Grade and myocardial blush grade. Patients and Methods a single center prospective randomized controlled trial based at the coronary care units in Ain shams university hospitals. The study included Three hundred Diabetic patients presenting to Ain shams university hospitals diagnosed with STEMI in the ER fulfilling the inclusion criteria were randomized to receive Ticagrelor (150 patients) or receiving clopidogrel (150 patients) Results As regard TIMI flow there was statistically highly significant highly significant difference between two studied groups with P value 0.000 where in group A 64 % of patients developed TIMI III flow, 22.7 % with TIMI II flow, 12.7% with TIMI I and 0.7% with TIMI 0 While in group B 86% of patients developed TIMI III flow, 9.3% of them developed TIMI II, 3.3 % developed TIMI I flow and 1.3 % developed TIMI 0. As regard MBG there was statistically highly significant difference between two groups with P value 0.00 where in group A where percentage of patients with MBG grades 0,1,2 and 3 were 4%, 16 %,18 % and 62 % respectively while in group B percentage of patients with MBG grades 0,1,2 and 3 were 1.3 %, 3.3 %, 9.3 % and 86 % respectively. As regard echo EF, there was statistically significant difference between two groups with P value 0.036 where mean EF in patients with group A was 40.50 ± 7.93 while the mean EF in patients with group B was 42.55 ± 8.88 . Conclusion Ticagrelor loading before primary PCI resulted in improved post-procedural TIMI flow. It also increased the post-procedural MBG. This resulted in a significant increase in the number of patients having more post-procedural Ejection fraction as measured by modified Simpson’s method. However, it did not decrease incidence of in-hospital MACE. Also there was no significant increase in risk of major nor minor bleeding in both young and elderly patients.

Ticagrelor versus Clopidogrel in Prevention of No Reflow after 1ry PCI in Diabetic Patients with STEMI

Abstract Background Adequacy of coronary flow can be judged upon using several methods like TIMI Grade and myocardial blush grade. No-reflow phenomenon, defined as incomplete reperfusion at the microvascular level despite adequate patency of the occluded artery, remains an important limitation of primary percutaneous intervention in STEMI patients nowadays. We aim in this study to investigate the relationship between the antiplatelet loading dose whether to be Ticagrelor or Clopidogrel and post intervention coronary flow, bleeding risk in these patients. Aim of the Work To compare between the effects of preoperative loading dose of Ticagrelor and clopidogrel in Diabetic STEMI patients undergoing primary percutaneous coronary intervention regarding prevention of no reflow, Instent thrombosis and short term bleeding risk. Myocardial reperfusion was judged upon using TIMI Grade and myocardial blush grade. Patients and Methods a single center prospective randomized controlled trial based at the coronary care units in Ain shams university hospitals. The study included Three hundred Diabetic patients presenting to Ain shams university hospitals diagnosed with STEMI in the ER fulfilling the inclusion criteria were randomized to receive Ticagrelor (150 patients) or receiving clopidogrel (150 patients) Results As regard TIMI flow there was statistically highly significant highly significant difference between two studied groups with P value 0.000 where in group A 64 % of patients developed TIMI III flow, 22.7 % with TIMI II flow, 12.7% with TIMI I and 0.7% with TIMI 0 While in group B 86% of patients developed TIMI III flow, 9.3% of them developed TIMI II, 3.3 % developed TIMI I flow and 1.3 % developed TIMI 0. As regard MBG there was statistically highly significant difference between two groups with P value 0.00 where in group A where percentage of patients with MBG grades 0,1,2 and 3 were 4%, 16 %,18 % and 62 % respectively while in group B percentage of patients with MBG grades 0,1,2 and 3 were 1.3 %, 3.3 %, 9.3 % and 86 % respectively. As regard echo EF, there was statistically significant difference between two groups with P value 0.036 where mean EF in patients with group A was 40.50 ± 7.93 while the mean EF in patients with group B was 42.55 ± 8.88 . Conclusion Ticagrelor loading before primary PCI resulted in improved post-procedural TIMI flow. It also increased the post-procedural MBG. This resulted in a significant increase in the number of patients having more post-procedural Ejection fraction as measured by modified Simpson’s method. However, it did not decrease incidence of in-hospital MACE. Also there was no significant increase in risk of major nor minor bleeding in both young and elderly patients.

Sex-specific aspects on prognosis after aortic valve replacement for aortic stenosis: a SWEDEHEART registry study

ObjectiveTo compare long-term cardiovascular (CV) outcomes between men and women with aortic stenosis (AS) undergoing aortic valve replacement (AVR) by the type of valve implant.MethodsThe study population consisted of 14...

Evaluating the safety and effectiveness of direct oral anticoagulants compared with warfarin in very elderly patients with atrial fibrillation with and without low bodyweight

BackgroundLimited data exist on the safety and effectiveness of using direct oral anticoagulants (DOACs) in patients with atrial fibrillation aged 80 years or more with and without low bodyweight (LBW). ObjectivesWe aimed to evaluate the safety and effectiveness of using DOACs in this population compared with warfarin. MethodsThis retrospective active comparator new-user cohort study included veteran patients with atrial fibrillation who were newly initiated on either warfarin or DOACs between January 1, 2015, and January 1, 2021. The primary outcome was incidence of major bleeding and ischemic stroke. All outcomes were compared between treatment groups in 2 propensity score–matched cohorts of patients aged 80 years older with (AW) and without LBW (age-only cohort). Cox proportional hazard models were used to estimate adjusted hazard ratios (aHRs). ResultsMatched AW and age-only cohorts included 493 and 11 909 patients, respectively, in each of the DOAC and warfarin exposure groups. Greater than 90% were male, with a mean age of ∼87 years. The rate of major bleeding was lower in the DOAC group compared with warfarin in both the AW (aHR, 0.63; 95% CI, 0.46-0.87) and age-only cohorts (aHR, 0.58; 95% CI, 0.49-0.77). A significantly lower rate of ischemic stroke occurred in the DOAC group compared with warfarin in the AW cohort (aHR, 0.62; 95% CI, 0.45-0.84) and age-only cohort (aHR, 0.63; 95% CI, 0.58-0.68). ConclusionDOAC use was associated with lower risk of major bleeding and ischemic stroke compared with warfarin in patients aged 80 years or older with and without LBW.

Informing the United States Medicare Drug Price Negotiation for Apixaban and Rivaroxaban: Methodological Considerations for Value Assessments Many Years After Launch

ObjectivesTo demonstrate how health technology assessment methods can be used to support Medicare’s price negotiations for apixaban and rivaroxaban. MethodsFollowing the statutory outline of evidence that will be considered by Medicare, we conducted a systematic literature review, network meta-analyses, and decision analyses to evaluate the health outcomes and costs associated with apixaban and rivaroxaban compared with warfarin and dabigatran for patients with nonvalvular atrial fibrillation. Our methods inform discussions about the therapeutic impact of apixaban and rivaroxaban and suggest price premiums above their therapeutic alternatives over a range of cost-effectiveness thresholds. ResultsNetwork meta-analyses found apixaban resulted in a lower risk of major bleeding compared with warfarin and dabigatran and a lower risk of stroke/systemic embolism compared with warfarin but not compared with dabigatran. Rivaroxaban resulted in a lower risk of stroke/systemic embolism versus warfarin but not dabigatran, and there was no difference in major bleeding. Decision-analytic modeling of apixaban suggested annual price premiums up to $4350 above the price of warfarin and up to $530 above the price for dabigatran at cost-effectiveness thresholds up to $200 000 per equal value of life-years gained. Analyses of rivaroxaban showed an annual price premium of up to $3920 above warfarin and no premium above that paid for dabigatran. ConclusionsAlthough health technology assessment is typically performed near the time of regulatory approval, with modifications, we produced comparative clinical and relative cost-effectiveness findings to help guide negotiations on a “fair” price for drugs on the market for over a decade.

Mechanical or biological prosthesis for aortic valve replacement in patients aged 45 to 74 years

ObjectiveThe selection of valve prostheses for patients undergoing surgical aortic valve replacement remains controversial. In this study, we compared the long-term outcomes of patients undergoing aortic valve replacement with biological or mechanical aortic valve prostheses. MethodsWe evaluated late results among 5762 patients aged 45 to 74 years who underwent biological or mechanical aortic valve replacement with or without concomitant coronary artery bypass from 1989 to 2019 at 4 medical centers. The Cox proportional hazards model was used to compare late survival; the age-dependent effect of prosthesis type on long-term survival was evaluated by an interaction term between age and prosthesis type. Incidences of stroke, major bleeding, and reoperation on the aortic valve after the index procedure were compared between prosthesis groups. ResultsOverall, 61% (n = 3508) of patients received a bioprosthesis. The 30-day mortality rate was 1.7% (n = 58) in the bioprosthesis group and 1.5% (n = 34) in the mechanical group (P = .75). During a mean follow-up of 9.0 years, the adjusted risk of mortality was higher in the bioprosthesis group (hazard ratio, 1.30, P < .001). The long-term survival benefit associated with mechanical prosthesis persisted until 70 years of age. Bioprosthesis (vs mechanical prosthesis) was associated with a similar risk of stroke (P = .20), lower risk of major bleeding (P < .001), and higher risk of reoperation (P < .001). ConclusionsCompared with bioprostheses, mechanical aortic valves are associated with a lower adjusted risk of long-term mortality in patients aged 70 years or less. Patients aged less than 70 years undergoing surgical aortic valve replacement should be informed of the potential survival benefit of mechanical valve substitutes.

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

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

Apixaban Versus Vitamin K Antagonists in Patients With Antiphospholipid Syndrome: A Cohort Study.

Current guidelines recommend that direct anticoagulants should not be used in prevention of recurrent thrombosis in patients with antiphospholipid syndrome (APS). However, except for triple-positive APS and rivaroxaban use, little evidence supports such recommendation. In a real-life cohort study, we evaluated the risk of thromboembolism and bleeding in patients with APS on apixaban versus vitamin K antagonists (VKA). We enrolled 152 patients with APS (aged 44 years [interquartile range 36-56], 83% women), including 66 patients treated with apixaban 5 mg bid and 86 with warfarin (target international normalized ratio [INR] 2-3). During a median follow-up of 53 months, we recorded venous thromboembolism, ischemic stroke, or myocardial infarction, along with major bleeding. We observed 4 thrombotic events (6.1%, 3 venous thromboembolism and 1 ischemic stroke) in patients on apixaban and 12 events (14%, 9 venous thromboembolism, 2 ischemic strokes and 1 myocardial infarction) in VKA patients. Patients with APS on apixaban had similar risk of recurrent thromboembolism compared with those on warfarin (hazard ratio [HR] = 0.327, 95% confidence interval [CI]: 0.104-1.035). Thromboembolic events occurred less commonly in statin users (8% vs. 50%, P = 0.01) and more frequently in triple-positive APS (50% vs. 22.1%, P = 0.028) and in patients with higher D-dimer at baseline ( P = 0.023); the latter difference was present in the apixaban group ( P = 0.02). Patients on apixaban had similar risk of major bleeding compared with warfarin (HR = 0.54, 95% CI: 0.201-1.448). In real-life patients with APS, apixaban appears to be similar to VKA for the prevention of thromboembolism and risk of bleeding, which might suggest that some patients with APS could be treated with apixaban.

Laparoscopic Partial Splenectomy May Be Valuable for the Diagnosis of Malignant Lymphoma: A Case Report.

Diagnosing primary splenic malignant lymphoma (PSML) is challenging due to the non-specific nature of splenomegaly, necessitating splenic biopsy for confirmation. However, performing partial splenic resection for diagnostic purposes is an elective procedure due to the risk of major hemorrhage. Despite the longstanding practice of splenectomy over the past few decades, it remains invasive and may result in severe early or late complications. Hence, we present laparoscopic partial splenectomy (LPS) in a patient suspicious of PSML for diagnostic purposes in this study. An 81-year-old woman presented to our hospital with a one-month history of fever and dry cough. Atypical cells had been detected in her peripheral blood nine months ago. However, at that time, a bone marrow examination did not reveal any atypical cells. The laboratory tests revealed a soluble interleukin receptor-2 levels of 4,667 U/dl and atypical cells were also found in peripheral blood. Abdominal computed tomography showed splenomegaly without any other relevant findings. These findings are suspicious of PSML and LPS without vessel ligation was performed and a small fraction of the spleen from the inferior pole measuring 1.8×1.0 cm was resected. The operation lasted for 63 min with minimal estimated blood loss. Histopathological findings were compatible with the diagnosis of diffuse B-cell lymphoma. The postoperative clinical course was uneventful, and splenomegaly demonstrated improvement six months after the operation. LPS without vessel ligation for biopsy may be valuable for the diagnosis of malignant lymphoma, particularly when there are no swollen lymph nodes, as it offers a less invasive approach.

Safety and Efficacy of Rivaroxaban-Aspirin Combination Compared to Aspirin Monotherapy on Lower Peripheral Artery Disease after Revascularization: Systematic Review and Meta-analyses

Introduction. Currently, single antiplatelet treatments using aspirin or clopidogrel are recommended for post-revascularization peripheral artery disease (PAD) patients. However, a recent study suggested that a combination of rivaroxaban and aspirin was more favorable to use. We conducted a systematic review to determine the efficacy and safety of rivaroxaban and aspirin combination compared to aspirin alone. Method. A systematic review conducted based on the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) protocol. Search using keywords was conducted on Cochrane, PubMed, Scopus, EBSCOHost, and Google Scholar. Inclusion and exclusion criteria were applied. Selected studies were appraised using the Cochrane risk of bias tool v.2 for inclusion. The studies included were extracted for characteristics and outcomes. Outcomes were analyzed qualitatively and quantitatively. We used a fixed- or random-effect model to determine the pooled ratio per appropriate. A 95% confidence interval and p-value of 0.05 and below were used as indicators of statistical significance. Results. Two multicentered, randomized controlled studies were included after searching. They were appraised with a low risk of bias. Both studies showed greater primary effectivity outcomes in the combination group and improvements in major bleeding risk. The quantitative analysis found lower PAD complications rate (OR = 0.79; 95% CI = 0.66–0.95), which included myocardial infarction, stroke, cardiovascular death, and acute limb ischemia. The combination group provided lesser primary (OR = 1.32; 95% CI = 1.06–1.67) and secondary (OR = 1.47; 95% CI = 1.19–1.84) safety outcomes. Conclusion. A combination of rivaroxaban and aspirin provided better clinical outcomes in post-revascularization PAD patients. However, this combination should be used carefully as this yields a more significant risk of bleeding in the population.

Atrial High-Rate Episodes in Elderly Patients: The Anticoagulation Therapy Dilemma.

Atrial fibrillation (AF) has been associated with higher morbidity and mortality rates, especially in older patients. Subclinical atrial fibrillation (SCAF) is defined as the presence of atrial high-rate episodes (AHREs) > 190 bpm for 10 consecutive beats > 6 min and <24 h, as detected by cardiac implanted electronic devices (CIEDs). The selection of eligible patients for anticoagulation therapy among elderly individuals with AHREs detected through CIEDs remains a contentious issue. The meta-analysis of ARTESiA and NOAH-AFNET 6 clinical trials revealed that taking Edoxaban or Apixaban as oral anticoagulation therapy can reduce the risk of stroke by approximately 32% while increasing the risk of major bleeding by approximately 62%. However, it is still unclear which are, among patients with SCAF, those who can take the highest net clinical benefit from anticoagulant therapy. The present review summarizes the current evidence on this intriguing issue and suggests strategies to try to better stratify the risk of stroke and systemic embolism in patients with AHREs. We propose incorporating some parameters including chronic kidney disease (CKD), obesity, enlarged left atrial volume, the efficacy in blood pressure management, and frailty into the traditional CHA2DS2-VASc score. Future trials will be needed to verify the clinical usefulness of the proposed prognostic score mainly in the view of a personalized therapeutic approach in patients with SCAF.

Deaths and major cardiovascular events in patients with lymphoma: Analysis from a French nationwide hospitalization database

BackgroundThere are few data assessing the risk of death and cardiovascular events in patients with lymphoma. AimUsing a nationwide hospitalization database, we aimed to address cardiovascular outcomes in patients with lymphoma. MethodsFrom 01 January to 31 December 2013, 3,381,472 adults were hospitalized in French hospitals; 22,544 of these patients had a lymphoma. The outcome analysis (all-cause or cardiovascular death, myocardial infarction, ischaemic stroke, bleedings, new-onset heart failure and new-onset atrial fibrillation) was performed over a 5-year follow-up period. Each patient with lymphoma was matched with a patient without a lymphoma or other cancer (1:1). A competing risk analysis was also performed. ResultsAfter adjustment on all risk factors, cardiovascular and non-cardiovascular co-morbidities, the subdistribution hazard ratios for all-cause death, major bleeding, intracranial bleeding, new-onset heart failure and new-onset atrial fibrillation were higher in patients with lymphoma; conversely, the subdistribution hazard ratios for cardiovascular death, myocardial infarction and ischaemic stroke were lower in patients with lymphoma. In the matched analysis, the risk of all-cause death (subdistribution hazard ratio 1.936, 95% confidence interval 1.881–1.992) and major bleeding (subdistribution hazard ratio 1.117, 95% confidence interval 1.049–1.188) remained higher in patients with lymphoma. ConclusionIn this large nationwide cohort study, patients with lymphoma had a higher incidence of all-cause death and major bleeding.

Efficacy and safety of rivaroxaban versus warfarin in the management of unusual site deep vein thrombosis: a retrospective cohort study.

Unusual site deep vein thrombosis (DVT) was defined as venous thromboembolism (VTE) occurring outside the conventional deep veins of the lower extremity or pulmonary arteries. However, the optimal anticoagulation therapy for unusual site DVT remained unclear. This study aims to evaluate the efficacy and safety of rivaroxaban in unusual site DVT. This retrospective cohort study enrolled consecutive patients at Nanjing Drum Tower Hospital between January 2011 and December 2021 who were diagnosed with unusual site DVT. Patients were divided into two groups based on their ultimate medication choice: the warfarin group and the rivaroxaban group. The demographic characteristics were recorded for all enrolled patients. Clinical outcomes included recurrent VTE, bleeding complications and major bleeding. A total of 1,088 patients were divided into warfarin (n = 514) and rivaroxaban (n = 574) groups. After the stabilized inverse probability of treatment weighting, Hazard Ratios for warfarin vs. rivaroxaban of recurrent VTE, bleeding complications and major bleeding were 0.52(95% CI: 0.25-1.08), 0.30(95% CI: 0.14-0.60), and 0.33 (95% CI, 0.13-0.74), respectively. Risk of clinical outcomes in specified subgroups for age, gender, renal function, thrombosis sites and diagnosis were assessed. The interaction of gender and treatment on major bleeding was significant (P for interaction = 0.062). Otherwise, there was no significant interaction between the other subgroups and the treatment group in terms of clinical outcomes. Compared with warfarin, rivaroxaban exhibited comparable efficacy for the anticoagulant treatment of unusual site DVT, associated with a lower risk of bleeding complications and major bleeding.

Long-term prognostic implications of brachial-ankle pulse wave velocity in patients undergoing percutaneous coronary intervention.

The long-term clinical effect of arterial stiffness in high-risk disease entities remains unclear. The prognostic implications of brachial-ankle pulse wave velocity (baPWV) were assessed using a real-world registry that included patients who underwent percutaneous coronary intervention (PCI). Arterial stiffness was measured using baPWV before discharge. The primary outcome was net adverse clinical events (NACE), defined as a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, or major bleeding. Secondary outcomes included major adverse cardiac and cerebrovascular events (MACCE: a composite of all-cause death, non-fatal myocardial infarction, or non-fatal stroke), and major bleeding. The outcomes were assessed over a 4-year period. Patients (n = 3,930) were stratified into high- and low-baPWV groups based on a baPWV cut-off of 1891 cm/s determined through time-dependent receiver operating characteristic curve analysis. baPWV was linearly correlated with 4-year post-PCI clinical events. The high baPWV group had a greater cumulative incidence of NACE, MACCE, and major bleeding. According to multivariable analysis, the high baPWV groups had a significantly greater risk of 4-year NACE (adjusted hazard ratio [HRadj]: 1.44; 95% confidence interval [CI]: 1.12-1.85; p = 0.004), MACCE (HRadj: 1.40; 95% CI: 1.07-1.83; p = 0.015), and major bleeding (HRadj: 1.94; 95% CI: 1.15-3.25; p = 0.012). In PCI-treated patients, baPWV was significantly associated with long-term clinical outcomes, including ischemic and bleeding events, indicating its value for identifying high-risk phenotypes.

Risk of recurrent venous thromboembolism and major bleeding according to risk factor profiles in Asian patients: a subgroup analysis EINSTEIN-Extension and EINSTEIN-CHOICE

BackgroundRisks of recurrence and major bleeding with extended anticoagulation in Asian patients with venous thromboembolism (VTE) are similar to those in non-Asian patients but risks according to baseline risk factor profiles is not well documented.MethodsSubgroup analysis of two randomized trials, which compared once-daily rivaroxaban (20 mg or 10 mg) with placebo or aspirin (100 mg) for extended treatment in Asian patients with VTE who had completed 6–12 months of anticoagulation. Index events were classified as unprovoked, provoked by major persistent risk factors, minor persistent risk factors, minor transient risk factors, or major transient risk factors. One-year cumulative risks of recurrent VTE were calculated for these risk factor profiles.Results367 patients received rivaroxaban, 159 aspirin, and 48 placebo. For patients with unprovoked VTE, one-year cumulative incidences of recurrence in the 202 patients given rivaroxaban, the 89 given aspirin and the 28 given placebo were 1.6%, 5.8%, and 14.8%, respectively. For patients with VTE provoked by minor persistent risk factors, these incidences were 0% in the 74 patients given rivaroxaban, 9.3% in the 36 given aspirin, and 0% in the 12 given placebo. No recurrent VTE occurred in patients with VTE provoked by major persistent or transient risk factors or minor transient risk factors. Rivaroxaban was not associated with a significant increase in major bleeding.ConclusionsRivaroxaban seems to be an effective and safe option for extended treatment in Asian patients, especially those presenting with unprovoked VTE. Subgroups of patients with provoked risk factors were too small to draw meaningful conclusions.Trial registrationNCT00439725 and NCT02064439.

Apixaban versus low molecular weight heparin in patients with cancer-associated venous thromboembolism: a systematic review and meta-analysis.

The optimal treatment regimen for patients with cancer-associated venous thromboembolism (CA-VTE) remains unclear. Therefore, the authors sought to compare the outcomes of (VKAs) versus direct apixaban and low molecular weight heparin (LMWH) in patients with CA-VTE. MEDLINE, Embase, and Cochrane Central databases were searched for randomized controlled trials (RCTs) and observational studies comparing the efficacy and safety of apixaban and LMWH in patients with CA-VTE. Major bleeding, clinically relevant non-major bleeding (CRNMB), recurrence of pulmonary embolism (PE), deep venous thrombosis (DVT) and bleeding-related mortality were among outcomes of interest. Mantel-Haenszel weighted random-effects model was used to calculate relative risks (RRs) with 95% CIs. The analysis included 12011 patients from 3 RCTs and 2 observational studies. Compared to LMWH, apixaban significantly decreased the risk of major bleeding [RR 0.67 (95% CI 0.54, 0.83); P=0.0003, I2=0%] without significantly changing the risk of clinically relevant non-major bleeding [RR 0.96 (95% CI 0.64, 0.1.45); P=0.85, I2=57%]. Patients on apixaban had a noticeably reduced the risk of recurrence of PE than those taking LMWH, according to a meta-analysis [RR 0.56 (95% CI 0.32, 0.99); P=0.05, I2=0%]. There was no discernible difference between apixaban and LMWH in bleeding-related mortality events [RR 0.20 (95% CI 0.01, 4.18); P=0.30, I2=NA%], and recurrence of DVT [RR 0.60 (95% CI 0.22, 1.59); P=0.23, I2=32%]. Due to its lower risk of severe bleeding and reduced PE recurrence, apixaban may be a preferable treatment option for CA-VTE, but additional research is required to validate these conclusions and evaluate its long-term efficacy and safety.

Pleiotropic Effects of Direct Oral Anticoagulants in Chronic Heart Failure and Atrial Fibrillation: Machine Learning Analysis.

Oral anticoagulant therapy (OAT) for managing atrial fibrillation (AF) encompasses vitamin K antagonists (VKAs, such as warfarin), which was the mainstay of anticoagulation therapy before 2010, and direct-acting oral anticoagulants (DOACs, namely dabigatran etexilate, rivaroxaban, apixaban, edoxaban), approved for the prevention of AF stroke over the last thirteen years. Due to the lower risk of major bleeding associated with DOACs, anticoagulant switching is a common practice in AF patients. Nevertheless, there are issues related to OAT switching that still need to be fully understood, especially for patients in whom AF and heart failure (HF) coexist. Herein, the effective impact of the therapeutic switching from warfarin to DOACs in HF patients with AF, in terms of cardiac remodeling, clinical status, endothelial function and inflammatory biomarkers, was assessed by a machine learning (ML) analysis of a clinical database, which ultimately shed light on the real positive and pleiotropic effects mediated by DOACs in addition to their anticoagulant activity.

Comparative Profiles of the WATCHMAN™ and Amplatzer™ Cardiac Plug/Amplatzer™ Amulet™ Devices for Left Atrial Appendage Closure in Non-valvular Atrial Fibrillation: A Comprehensive Systematic Review and Meta-analysis.

Atrial fibrillation (AF) is a prevalent cardiac arrhythmia marked by irregular and frequent tachycardic rhythms in the atria, affecting 1%-2% of the general population. The WATCHMAN™ device from Boston Scientific (Marlborough, MA, USA) and the Amplatzer™ Amulet™ device from Abbott (Chicago, IL, USA) are two devices used globally for left atrial appendage closure (LAAC) in non-valvular AF. A systematic search was conducted in PubMed, the Cochrane Library, and Elsevier's ScienceDirect literature databases to identify studies comparing the WATCHMAN™ procedure with Amulet™ device implantation for LAAC in patients with AF. The analyses were conducted using the random-effects model. A total of 20 studies were identified, with 18 falling into the category of observational studies and 2 being randomized controlled trials. A total of 6310 participants were included in this meta-analysis, with 3198 individuals (50.68%) assigned to the WATCHMAN™ procedure group and 3112 individuals (49.32%) allocated to the Amplatzer™ Cardiac Plug (ACP) group. The analysis revealed a higher risk of stroke associated with the WATCHMAN™ technique (relative risk [RR], 1.14), albeit without statistical significance. Conversely, the WATCHMAN™ approach led to a significantly lower risk of cardiac death (RR, 0.44; P = .04). Notably, the risks of all-cause mortality (RR, 0.89; 95% confidence interval [CI], 0.73-1.08; I 2 = 0%; P = .25) and major bleeding (RR, 0.93; 95% CI, 0.65-1.33; I 2 = 31%; P = .70) were clinically reduced with the WATCHMAN™ procedure, although statistical significance was not achieved. Compared to Amulet™ device implantation, WATCHMAN™ device implantation decreased the risk of cardiac mortality, while the risks of stroke, systemic embolism, all-cause mortality, and major bleeding were not statistically significant.