Higher Risk Of Major Bleeding Research Articles

Risk of Intracranial Hemorrhage Associated With Direct Oral Anticoagulation vs Antiplatelet Therapy

For patients with atrial fibrillation, clinicians often prescribe antiplatelet therapy rather than oral anticoagulation, which may be related to a concern that direct oral anticoagulants (DOACs) are associated with a higher risk of intracranial bleeding, despite being less effective for stroke prevention. To determine whether DOAC therapy, compared with single-agent antiplatelet therapy, was associated with an increased risk of intracranial and major hemorrhage. A systematic search of PubMed and Embase databases from inception to February 7, 2024, was performed. Randomized clinical trials that compared DOAC therapy with single-agent antiplatelet therapies were included. Trials with active follow-up of less than 30 days or a sample size less than 200 were excluded. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guideline. Data were extracted independently by 2 researchers. A random-effects meta-analysis model was used to report pooled treatment effects and 95% CIs. The primary outcome was occurrence of intracranial hemorrhage. A total of 9 randomized clinical trials were included (45 494 participants). DOAC therapy was not associated with significantly higher odds of intracranial hemorrhage compared with antiplatelet therapy (0.55% vs 0.48% over a mean trial follow-up of 17.1 months; odds ratio [OR], 1.15; 95% CI, 0.71-1.88), but there was heterogeneity among trials (I2 = 53.7%). In an analysis by DOAC agent, the respective estimates for intracranial hemorrhage risk were as follows: rivaroxaban, OR, 2.09 (95% CI, 1.20-3.64); dabigatran, OR, 1.00 (95% CI, 0.61-1.64); and apixaban, OR, 0.72 (95% CI, 0.44-1.17). Overall, DOAC therapy was associated with higher odds of major hemorrhage compared with antiplatelet therapy (2.41% vs 1.76% over a mean trial follow-up of 15.5 months; OR, 1.39; 95% CI, 1.07-1.80), with the following estimates by agent: rivaroxaban, OR, 1.91 (95% CI, 1.22-3.00); dabigatran; OR, 1.21 (95% CI, 0.86-1.69); and apixaban, OR, 1.09 (95% CI, 0.73-1.63). In this systematic review and meta-analysis, DOAC therapy was not associated with a significantly higher risk of intracranial hemorrhage compared with antiplatelet therapy, but was associated with a higher risk of major hemorrhage. These findings support the safety of DOAC compared with antiplatelet therapy with respect to risk of ICH and reinforce adherence with current atrial fibrillation guidelines.

Correlation between thrombocytopenia and adverse outcomes in patients with atrial fibrillation: a systematic review and meta-analysis.

Thrombocytopenia is often associated with adverse outcomes in patients with atrial fibrillation. Therefore, we conducted a meta-analysis to comprehensively assess the impact of thrombocytopenia on ischemic stroke/systemic embolism, major bleeding and all-cause mortality in patients with atrial fibrillation. Two electronic databases, PubMed and Web of Science, were systematically searched from their inception to December 1, 2023, including the studies on the correlation between atrial fibrillation patients with thrombocytopenia and adverse outcomes. Relevant data was extracted, literature quality was evaluated, meta-analysis was performed by using REVMAN 5.4 software, and the results were reported with odds ratio (OR) of 95% confidence interval (CI). A total of 12 studies included 73,824 patients with atrial fibrillation (average age: 72.67, males: 42,275, 57.3%), among them, there were 7,673 patients combined with thrombocytopenia. The average follow-up time of these studies was 87 days to 55 months. Compared to no thrombocytopenia, atrial fibrillation patients combined with thrombocytopenia have a significant risk reduction of ischemic stroke/systemic embolism [OR: 0.79, 95% CI: (0.69, 0.91); P < 0.01]. Nevertheless, the risk of both major bleeding [OR: 1.51, 95% CI: (1.20, 1.79), P < 0.01] and all-cause mortality [OR: 1.40, 95% CI: (1.23, 1.61); P < 0.01] is significantly higher in thrombocytopenia group. Thrombocytopenia has an important impact on the prognosis of patients with atrial fibrillation. Thrombocytopenia is significantly associated with a lower risk of ischemic stroke/systemic embolism but a higher risk of major bleeding and all-cause mortality. Attention to thrombocytopenia and optimization of treatment may be the effective way to improve the prognosis of atrial fibrillation with thrombocytopenia. https://www.crd.york.ac.uk/, PROSPERO Registration Number: (CRD42023459916).

Perioperative direct oral anticoagulant management during cardiac implantable electronic device surgery: an updated systematic review and meta-analysis.

Patients undergoing cardiovascular implantable electronic device (CIED) implantation are often on direct oral anticoagulation (DOAC). However, the evidence on whether to continue or temporarily discontinue DOAC therapy during the perioperative period in these patients is unclear. We conducted a comprehensive literature review using PubMed, Embase, and Cochrane databases through July 2024. We included studies comparing uninterrupted versus interrupted perioperative DOAC therapy in patients undergoing CIED procedure- primary implants, pulse generator replacement, and device upgrades. Primary outcomes were clinically significant device-pocket hematoma and thromboembolic events. Secondary outcomes included any device-pocket hematoma, all-cause mortality, major bleeding, and any bleeding. A total of 1,607 patients from 8 studies were included. The mean age was 73.2years, with atrial fibrillation as the indication for DOAC therapy in most patients. The mean CHA2DS2-VASc was 3.4. Among the included studies, 2 were randomized control trials (RCTs), while the others were observational cohort studies, including one that was propensity score matched. Our meta-analysis found both strategies to be similar in terms of clinically significant pocket hematoma (RR 1.70; 95%CI 0.84-3.45; p = 0.14; I2 = 0%), thromboembolic complications (RR 0.35; 95%CI 0.04-3.32; p = 0.36; I2 = 19%), any pocket hematoma, all-cause mortality and any bleeding with a higher risk of major bleeding with uninterrupted anticoagulation. This meta-analysis shows that uninterrupted DOAC therapy is comparable to interrupted therapy for CIED procedures, with a potential increase in major bleeding risk but low overall complication rates. Further research is needed to confirm the best approach of periprocedural anticoagulation in these patients.

Use of Aspirin and Initial Cardiovascular and Bleeding Risk in Patients with Chronic Kidney Disease

Background: Despite the high cardiovascular risk in patients with chronic kidney disease (CKD), the role of aspirin in primary prevention remains unclear. This study aimed to investigate the association between aspirin initiation in adults with CKD without prior cardiovascular disease (CVD) and the first cardiovascular and bleeding events using Korean nationwide cohort data. Methods: Among individuals aged 40–79 years with an estimated glomerular filtration rate between 15 and 59 mL/min/1.73 m2 who underwent routine health examinations between 2011 and 2016, 15,861 individuals who were newly prescribed aspirin at a dose of 100 mg/day were matched with 79,305 aspirin non-users by propensity score matching. The primary efficacy outcome was a composite of nonfatal atherosclerotic CVD or cardiovascular death. The primary safety outcome was hospitalization due to intracranial or gastrointestinal bleeding. Results: During a mean follow-up of 6.9±2.9 years, the incidence rates for the primary efficacy outcome in aspirin users and non-users were 8.0 and 9.0 per 1,000 person-years, respectively. Aspirin therapy initiation was not associated with the primary efficacy outcome (hazard ratio [HR], 0.93; 95% confidence intervals [CI], 0.86-1.04). However, the primary safety outcome of major bleeding was more frequent in aspirin users than in non-users (6.7 versus 4.7 per 1,000 person-years). The HR for this outcome in aspirin users versus non-users was 1.45 (95% CI, 1.32-1.59). Conclusions: No association was observed between aspirin use and the risk of nonfatal atherosclerotic CVD or cardiovascular death in patients with CKD stages G3 and G4 without prior CVD. Aspirin use was associated with higher risk of major bleeding.

Abstract 4136632: Impact of Postoperative Atrial Fibrillation on Long-term Clinical Outcomes in Patients after Coronary Artery Bypass Grafting

Background: The impact of postoperative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG) on long-term clinical outcomes has not been adequately evaluated yet. Methods: Among consecutive 14927 patients who underwent their first coronary revascularization in the CREDO-Kyoto PCI/CABG Registry Cohort-3 (2011-2013), the study population consisted of 1483 patients who underwent CABG after excluding those with prior AF. POAF was defined as newly documented AF during hospitalization for CABG. The primary outcome measure was all-cause death after discharge. The median clinical follow-up was 5.7 (interquartile range, 4.4-6.6) years. Results: POAF was observed in 337 patients (23%). Multivariable logistic regression analysis indicated that age &gt;=75 years (odds ratio [OR], 1.61; 95% confidence interval [CI], 1.24-2.10; P&lt;0.001) and cardiopulmonary bypass (CPB) use (OR, 1.40; 95%CI, 1.09-1.79; P=0.01) were independent predictors of POAF. Of the 1400 patients discharged alive among the study population, the POAF group included more older patients, patients with prior stroke, and patients prescribed beta-blockers and oral anticoagulants than the non-POAF group. The cumulative 5-year incidence of all-cause death was 15.9% in the POAF group and 13.0% in the non-POAF group (Log-rank P=0.38). After adjusting for confounders, the adjusted risk for all-cause death was almost neutral (adjusted HR, 0.96; 95%CI, 0.70-1.31; P=0.81). The cumulative 5-year incidence of stroke was significantly higher in the POAF group than in the non-POAF group (8.0% versus 4.2%; Log-rank P=0.02), and the adjusted risk of stroke in the POAF group relative to the non-POAF group tended to be higher (adjusted HR: 1.58, 95%CI, 0.99-2.53; P=0.057). However, the cumulative 5-year incidence of major bleeding was significantly higher in the POAF group than in the non-POAF group (14.6% versus 10.7%; Log-rank P=0.01). Even after adjusting for confounders, the excess risk of major bleeding in the POAF group was significant (adjusted HR, 1.42; 95%CI, 1.01-2.00; P=0.041). Conclusions: Advanced age and CPB use were associated with POAF occurrence. POAF was not associated with long-term mortality after discharge. However, it tended to be associated with a higher risk for stroke and was associated with a significantly higher risk for major bleeding. Further study would be needed to clarify the appropriate management of POAF after CABG.

Abstract 4135899: Large-Scale Investigation on the Outcomes of Atrial Fibrillation Ablation in Liver Cirrhosis Patients

Background: Catheter-based atrial fibrillation(AF) ablation is amongst the most commonly done EP procedures that have evolved over decades, improving patient outcomes and quality of life. Atrial fibrillation is seen in 5% of patients with cirrhosis and studies have shown AF in cirrhosis to be associated with increased mortality and adverse hospital outcomes. Aim: There is scarce literature on the outcomes of AF ablation in patients with cirrhosis. Our study aimed to study the safety and efficacy of catheter-based AF ablations in this population group and to ascertain if there is a difference compared to the general patient population. Methods: We used the Nationwide Inpatient Sample Database 2016-2020, the largest openly accessible inpatient healthcare database in the United States. Patients with a primary diagnosis of AF were identified using ICD-10 codes. We excluded patients with a secondary diagnosis of other arrhythmias, missing demographics, mortality, or age&lt;18. The study population was divided into patients with and without cirrhosis. Information was collected regarding various patient demographic characteristics and comorbidities (comorbidity burden captured via Elixhauser Comorbidity Index). The primary endpoint was in-hospital mortality. The secondary endpoints were total complications, length of stay, and hospitalization charges. Results: A total of 23,905 patients underwent ablation, with 23,800 being non-cirrhotic, and only 105 presenting with cirrhosis. This signifies a relatively low proportion of cirrhotic patients undergoing ablation procedures, approximately 0.6% (105 out of a total of 17,600 cirrhotic patients). Additionally, the Elixhauser comorbidity index is significantly higher in cirrhotic patients (6.62) compared to non-cirrhotic patients (3.65) with a p-value &lt;0.001, indicating a higher burden of comorbidities in the cirrhotic group. Patients with cirrhosis undergoing ablation procedures exhibit a notably higher risk of major bleeding compared to those without cirrhosis (14.3% vs. 4.06%, p-value = 0.02). Furthermore, the incidence of bleeding requiring transfusion is significantly elevated in cirrhotic patients (4.8%) in contrast to non-cirrhotic patients (0.2%) (p-value &lt; 0.001). Conclusion: Although the risk of major bleeding is high, overall mortality and other complications are comparable to those without cirrhosis. We believe that this can be mitigated by carefully selecting the patients with cirrhosis for this procedure.

Abstract 4135791: Bleeding risk with non-vitamin K antagonist oral anticoagulants versus single antiplatelet therapy: A systematic review and meta-analysis of randomized controlled trials

Background: While non-vitamin K antagonist oral anticoagulants (NOACs) are more effective than single antiplatelets (mostly low-dose aspirin) at reducing stroke risk in patients with atrial fibrillation (AF), differences in bleeding risk between NOACs and single-dose antiplatelets across various populations remain unclear. Aim: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing bleeding outcomes of NOACs versus single antiplatelet therapy. Methods: We searched MEDLINE, EMBASE, and CENTRAL to June 2024 for RCTs that compared NOAC (therapeutic doses used for stroke prevention in AF patients) versus single antiplatelet therapy for a treatment duration of ≥3 months. For the meta-analyses, we used fixed-effects models and reported results as summary risk ratios (RRs). We used Risk of Bias 2 and GRADE to assess the quality and certainty of the evidence. Results: Eight RCTs with 26,194 participants were included. Mean follow-up time was 18 (±13) months. NOACs included in the studies were apixaban (4 studies), rivaroxaban (2 studies), and dabigatran (2 studies). All studies used low-dose aspirin as the comparator. When compared to aspirin, NOACs had a higher risk of major bleeding (326/13107 [2.5%] vs. 239/13087 [1.8%] events; RR 1.36 95% CI 1.15-1.60, I 2 =52%, 8 trials; high certainty) (Figure A), gastrointestinal bleeding (104/8803 [1.2%] vs. 74/8788 [0.8%] events; RR 1.39; 95%CI, 1.04-1.87; I 2 =0%; 5 trials; high certainty), and clinically relevant non-major bleeding (318/10397 [3.1%] vs. 230/10395 [2.2%] events; RR 1.38; 95%CI, 1.17-1.63; I 2 =16%; 5 trials; high certainty). There was no difference in the risk of intracranial hemorrhage (88/13107 [0.7%] vs. 84/13087 [0.6%] events; RR 1.04, 95%CI 0.78-1.41; I 2 =48%; 9 trials; high certainty) (Figure B) nor fatal bleeding (22/12412 [0.2%] vs. 28/12392 [0.2%] events; RR 0.78; 95%CI, 0.45-1.36; I 2 =8%; 6 trials; high certainty). Conclusion: When compared to aspirin, NOACs are associated with an increased risk of major bleeding and clinically relevant non-major bleeding, but not intracranial hemorrhage. These data are important to inform patients about the risks of antithrombotic treatment.

Abstract 4116425: " Navigating High-Risk Terrain: Clinical Outcomes of Percutaneous Coronary Intervention (PCI) in Breast Cancer Patients - A National Inpatient Sample Analysis "

Background: Breast cancer is the most prevalent malignancy affecting women globally and is one of the leading causes of cancer-related deaths. Cardiovascular disease (CVD) holds the highest mortality rate among women. However, the prognosis of percutaneous coronary intervention (PCI) patients with underlying breast cancer has not been well-studied. Methods: The National Inpatient Sample (NIS) 2017-2020 database was used to identify PCI patients with ICD-10 codes for a retrospective analysis. PCI patients were then divided into those with and without underlying breast cancer. Multivariable logistic regression was performed for composite post-PCI outcomes analyses. Results: Among 2,815,610 patients admitted for PCI, 3,935 had breast cancer. Patients with underlying breast cancer experienced worse post-PCI outcomes, including a higher risk of major bleeding (OR, 3.7; 95% CI, 2.9 - 4.8; P &lt; .001) and post-PCI cardiac arrest (OR, 8.003; 95% CI, 5.39 - 11.8). The need for devices such as Impella and IABP was also higher in the breast cancer subpopulation compared to those without (OR, 6.8; 95% CI, 5.7 - 8.0) and (OR, 8.4; 95% CI, 7.44 - 9.668), respectively. Although the incidence of stroke was higher in the subpopulation, intra/post-PCI stroke was lower. Breast cancer patients undergoing PCI showed no significant difference in hospitalization charges or length of stay. Conclusions: In conclusion, our study sheds light on the intricate relationship between breast cancer and percutaneous coronary intervention (PCI) outcomes. These findings underscore the importance of tailored care and close monitoring for breast cancer patients undergoing PCI.

Oral anticoagulants or antiplatelets for cryptogenic stroke: a systematic review and meta-analysis

Abstract Background Cryptogenic strokes comprise 20 to 30% of ischemic strokes and include a substantial proportion classified as embolic stroke of undetermined source (ESUS). However, the optimal antithrombotic strategy for cryptogenic stroke remains contentious. Purpose We conducted a systematic review and meta-analysis to compare the efficacy and safety of oral anticoagulants (OAC) versus antiplatelets in patients with cryptogenic stroke. Methods Six electronic databases of PubMed, Embase, Web of Science, the Cochrane Library, Google Scholar and ClinicalTrials.gov were searched from inception to Feb 15, 2024 to identify relevant randomized controlled trials (RCTs) comparing stroke recurrence and major bleeding rates between OAC and antiplatelets in cryptogenic stroke patients. We included trials adhering to a stringent diagnostic work-up for cryptogenic stroke, defined as cerebral infarction not attributed to definite sources of cardioembolism, large artery atherosclerosis, or small artery disease despite undergoing comprehensive investigations. The primary outcome was recurrent ischemic stroke, and the secondary outcome was major bleeding based on International Society of Thrombosis and Hemostasis criteria. Subgroup analysis was conducted for ESUS patients with an increased risk of cardiac emboli, such as patent foramen ovale (PFO) and atrial cardiopathy, defined as lead V1 terminal P-wave &amp;gt; 5000 μV × ms in electrocardiogram, serum N-terminal pro-B-type natriuretic peptide level &amp;gt; 250 pg/mL, and left atrial diameter (LAE) &amp;gt; 4 cm, or LAE index ≥ 3 cm/m2 on echocardiogram. Hazard ratio (HR) with 95% confidence (CI) was used as a measure of the effect estimates for aforementioned outcomes. Random-effects meta-analysis was performed using a restricted maximum likelihood model given between-study variance is inevitable. Results Our meta-analysis included 9 RCTs with a total of 15,139 patients (OAC = 7,343; antiplatelets = 7,796). ARCADIA, RE-SPECT ESUS, and NAVIGATE ESUS Trial investigated apixaban, dabigatran, and rivaroxaban, respectively, while warfarin was primarily used as OAC in the remaining six trials. Aspirin was predominantly utilized for antiplatelet therapy. There was no significant difference in recurrent ischemic stroke between OAC and antiplatelets (HR, 0.90; 95% CI, 0.78 to 1.04; I2 = 0%). However, OAC use was associated with a significantly higher risk of major bleeding (HR, 1.66; 95% CI, 1.07 to 2.56; I2 = 36%). Subgroup analysis in ESUS patients revealed comparable rates of recurrent ischemic stroke in those with atrial cardiopathy (HR, 0.91; 95% CI, 0.65 to 1.29; I2 = 0%) and PFO (HR, 0.72; 95% CI, 0.49 to 1.07; I2 = 0%). Conclusions Our meta-analysis suggests that OAC use does not decrease the risk of recurrent ischemic stroke compared with antiplatelet use but is associated with a significantly higher risk of major bleeding in patients with cryptogenic stroke.Primary (A) and secondary (B) outcomesSubgroup analysis for recurrent stroke

Switching from warfarin to a DOAC in frail elderly asian patients with atrial fibrillation: a nationwide population-based study

Abstract Background Recently, switching international normalized ratio guided warfarin management to a direct oral anticoagulant (DOAC) was associated with more bleeding complications than maintaining warfarin in frail elderly patients with atrial fibrillation (AF). However, there is a paucity of information on whether these results could be applied to Asian patients with AF, who are known to have relatively low time in therapeutic range (TTR) levels. Purpose To evaluate the safety and effectiveness of switching from warfarin to a DOAC in frail elderly Asian patients with AF. Methods Using a Korean health insurance database, we included patients with AF who were prescribed warfarin between January 2013 and August 2015 without significant bleeding or thromboembolic events during the window period, specifically those aged 75 or older with a Hospital Frailty Risk Score of 5 or more. Those who switched to DOACs during the window period were categorized as the DOAC group and those who continued with warfarin were categorized as the warfarin group. The primary outcome was defined as the composite of major bleeding (MB) and clinically relevant non-major bleeding (CRNMB), and secondary outcomes were defined as thromboembolic events, all-cause death, the composite of MB, CRNMB and ischemic stroke (so-called net clinical outcome [NCO]). The propensity score weighting method was utilized to compare the two groups. Results A total of 12,162 patients were included (8,108 with maintaining warfarin, 4,054 with switching to a DOAC). Baseline characteristics were well-balanced after the inverse probability of treatment weighting (mean age, 80 years; men, 50%; and mean CHA₂DS₂-VASc score, 5.6). Compared with maintaining warfarin, switching to a DOAC was associated with significantly higher risks of the primary outcome (hazard ratio [HR] 1.43, 95% confidence interval [CI] 1.09-1.87, p=0.01), thromboembolic events (1.28, 1.01-1.62, p=0.039), all-cause death (1.38, 1.15-1.66, p&amp;lt;0.001) and the NCO (1.26, 1.01-1.58, p=0.04). (Figure A, Figure B), whereas there was no difference in the risk of intracerebral hemorrhage (0.90, 0.50-1.60, p=0.7157). When comparing each DOAC with maintaining warfarin, switching to rivaroxaban was associated with a higher risk of the composite of MB and CRNMB (1.91, 1.38-2.64, p&amp;lt;0.001) and thromboembolic events (1.40, 1.03-1.91, p=0.034) than maintaining warfarin. Conclusion In line with the non-Asian population, switching to a DOAC was associated with a significantly higher risk of MB or CRNMB, thromboembolic events, all-cause death and NCO compared with maintaining warfarin in frail elderly Asian patients with AF. Therefore, even in Asians, switching to a DOAC should be considered more cautiously in patients who are stably managed on warfarin.

A systematic review and meta-analysis of the efficacy and safety of combined mechanical circulatory support in cardiogenic shock complicating acute myocardial infarction

Abstract Background Cardiogenic shock complicating acute myocardial infarction (CSAMI) is a severe complication associated with unacceptably high mortality rates. Since early revascularisation was introduced more than 20 years ago, no subsequent innovation has demonstrated conclusive efficacy in reducing mortality in CSAMI. While mechanical circulatory support (MCS) has emerged as a potential intervention, randomised controlled trials evaluating independent use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO), and intra-aortic balloon pump (IABP) have not shown benefit in CSAMI. In contrast, systematic reviews of observational studies have revealed significant mortality reduction when CSAMI was treated with combined use of MCS, specifically VA-ECMO in conjunction with a left ventricular (LV) unloading device (Impella or IABP). Combination MCS (VA-ECMO + LV unloading) may therefore present a promising approach to CSAMI, but an unresolved dilemma concerning the optimal selection between two LV unloading devices (VA-ECMO + Impella vs VA-ECMO + IABP) warrants further investigation and clarification. Purpose We perform the first systematic review and meta-analysis assessing the short-term efficacy and safety of VA-ECMO + Impella versus VA-ECMO + IABP in treatment of CSAMI. Methods A systematic search was performed on the EMBASE and MEDLINE databases. Studies reporting the short-term (30-day/inpatient) mortality and complications of adult patients with CSAMI treated with VA-ECMO + Impella and VA-ECMO + IABP were included. Fixed effect meta-analyses using Mantel-Haenszel model was used to analyse the pooled odds ratio for short-term mortality and major complications. Subgroup analysis was performed including studies with ACS predominant CS (Cause of CS 100% by AMI). Results Four observational studies with 14,247 patients were included. These studies showed high heterogeneity for the total CSAMI cohort and low heterogeneity for the ACS predominant cohort. There was no significant difference in mortality between VA-ECMO + Impella and VA-ECMO + IABP 56.5% vs 66.5%; OR, 0.90; 95% CI, 0.79–1.02; P=0.09. However, VA-ECMO + Impella was associated with significantly lower mortality in patients with ACS predominant CS 53.2% vs 67.7%; OR, 0.72; 95% CI, 0.62–0.85; P&amp;lt;0.0001. VA-ECMO + Impella was associated with significantly higher risk of major bleeding 15.1% vs 8.6%; OR, 1.87; 95% CI, 1.50–2.32; P&amp;lt;0.00001 and vascular complications 15.0% vs 6.7%; OR, 1.75; 95% CI, 1.41–2.18; P&amp;lt;0.00001. Conclusions When comparing LV unloading devices in patients with CSAMI requiring combination MCS, VA-ECMO + Impella was superior in mortality reduction only in the cohort where 100% of CS was caused by AMI. Concomitantly, VA-ECMO + Impella was associated with greater risk of major bleeding and vascular complications. Additional randomised studies are needed to validate and strengthen the findings presented in these observational data.Forrest plot on short-term mortalityForrest plot on major complications

Ischemic and bleeding risk after ST-segment elevated myocardial infarction in patients with active cancer

Abstract Background Treatment of patients with cancer presenting with ST-elevation myocardial infarction (STEMI) is complex given the increased risk of both thrombotic and major bleeding complications. We evaluated the risk of major bleeding and re-infarction in patients with or without cancer following admission with STEMI Methods A nationally-linked cohort of STEMI patients between January 2005 and March 2019 were obtained from the UK Myocardial Infarction National Audit Project (MINAP) registry and the UK national Hospital Episode Statistics Admitted Patient Care (HES APC) registry. Cox proportional hazard models were used, and Kaplan-Meier survival and cumulative survival curves were constructed. Results A total of 322,776 STEMI indexed admissions were identified between Jan 2005 and March 2019. Of those, 7050 (2.2%) patients were diagnosed with active cancer. Cancer patients were older with more cardiovascular comorbidities. Cancer patients received invasive coronary angiography (62.2% vs 72.7%, p&amp;lt;0.001) and PCI (58.4% vs 69.5%) less often compared to patients without cancer and were less likely to be prescribed DAPT (85% vs 95.4%). Major bleeding rate at one year was higher in cancer patients (6.5% vs 3.5%) while re-infarction rates were similar (cancer 5.7%, no cancer 5.1%). Adjustment for differences in baseline covariates, a similar risk of re-infarction (SHR 1.10, 95% CI 0.94-1.27) and a 50% increased risk of major bleeding (SHR 1.49, 95% CI 1.30-1.71) was observed in cancer patients. Conclusion Compared to non-cancer patients, cancer patients have a higher risk of major bleeding but not of re-infarction. Mitigating bleeding risk in STEMI patients with cancer is of paramount importance to improve outcomes.bleeding risk at 1 yearRe-infarction risk at 1 year

Prediction model for major bleeding in anticoagulated patients with cancer-associated venous thromboembolism using machine learning and natural language processing.

We developed a predictive model to assess the risk of major bleeding (MB) within 6 months of primary venous thromboembolism (VTE) in cancer patients receiving anticoagulant treatment. We also sought to describe the prevalence and incidence of VTE in cancer patients, and to describe clinical characteristics at baseline and bleeding events during follow-up in patients receiving anticoagulants. This observational, retrospective, and multicenter study used natural language processing and machine learning (ML), to analyze unstructured clinical data from electronic health records from nine Spanish hospitals between 2014 and 2018. All adult cancer patients with VTE receiving anticoagulants were included. Both clinically- and ML-driven feature selection was performed to identify MB predictors. Logistic regression (LR), decision tree (DT), and random forest (RF) algorithms were used to train predictive models, which were validated in a hold-out dataset and compared to the previously developed CAT-BLEED score. Of the 2,893,108 cancer patients screened, in-hospital VTE prevalence was 5.8% and the annual incidence ranged from 2.7 to 3.9%. We identified 21,227 patients with active cancer and VTE receiving anticoagulants (53.9% men, median age of 70years). MB events after VTE diagnosis occurred in 10.9% of patients within the first six months. MB predictors included: hemoglobin, metastasis, age, platelets, leukocytes, and serum creatinine. The LR, DT, and RF models had AUC-ROC (95% confidence interval) values of 0.60 (0.55, 0.65), 0.60 (0.55, 0.65), and 0.61 (0.56, 0.66), respectively. These models outperformed the CAT-BLEED score with values of 0.53 (0.48, 0.59). Our study shows encouraging results in identifying anticoagulated patients with cancer-associated VTE who are at high risk of MB.

Risk of Major Bleeding, Stroke/Systemic Embolism, and Death Associated With Different Oral Anticoagulants in Patients With Atrial Fibrillation and Severe Chronic Kidney Disease.

Patients with atrial fibrillation and severe chronic kidney disease have higher risks of bleeding, thromboembolism, and mortality. However, optimal anticoagulant choice in these high-risk patients remains unclear. Using deidentified electronic health records from the Optum Labs Data Warehouse, adults with atrial fibrillation and severe chronic kidney disease (estimated glomerular filtration rate <30 mL/min per 1.73 m2) initiating warfarin, apixaban, or rivaroxaban between 2011 and 2021 were included. Using inverse probability of treatment weighting, adjusted risks of major bleeding, stroke/systemic embolism, and death were compared among agents. A total of 6794 patients were included (mean age, 78.5 years; mean estimated glomerular filtration rate, 24.7 mL/min per 1.73 m2; 51% women). Apixaban versus warfarin was associated with a lower risk of major bleeding (incidence rate, 1.5 versus 2.9 per 100 person-years; subdistribution hazard ratio [sub-HR], 0.53 [95% CI, 0.39-0.70]), and similar risks for stroke/systemic embolism (incidence rate, 1.9 versus 2.4 per 100 person-years; sub-HR, 0.80 [95% CI, 0.59-1.09]) and death (incidence rate, 4.6 versus 4.5 per 100 person-years; HR, 1.03 [95% CI, 0.82-1.29]). Rivaroxaban versus warfarin was associated with a higher risk of major bleeding (incidence rate, 4.9 versus 2.9 per 100 person-years; sub-HR, 1.65 [95% CI, 1.10-2.48]), with no difference in risks for stroke/systemic embolism and death. Apixaban versus rivaroxaban was associated with a lower risk of major bleeding (sub-HR, 0.53 [95% CI, 0.36-0.78]). These real-world findings are consistent with potential safety advantages of apixaban over warfarin and rivaroxaban for patients with atrial fibrillation and severe chronic kidney disease. Further randomized trials comparing individual oral anticoagulants are warranted.

Comparative effectiveness of antiplatelet therapies for saphenous venous graft occlusion and cardiovascular outcomes: a network meta-analysis.

The ideal antiplatelet therapy to maintain graft patency after coronary artery bypass graft surgery (CABG) remains controversial. This review of randomized controlled trials (RCTs) aims to compare aspirin monotherapy, ticagrelor monotherapy, dual antiplatelet therapy (DAPT) with aspirin and ticagrelor (Asp+Tica) or with aspirin and clopidogrel (Asp+Clopi) to evaluate differences in post-CABG saphenous vein graft (SVG) occlusion, internal mammary artery (IMA) occlusion, myocardial infarction (MI), bleeding, and all-cause mortality (ACM) rates. The literature review was conducted on several electronic databases, including Medline, Embase, and Cochrane Central, from inception to August 10, 2022. Data was extracted using a predefined proforma. A Bayesian random-effects model was used for calculating point effect estimates (odds ratio and standard deviation). Quality assessment was done using the Cochrane RoB-2 tool. Ten RCTs comprising 2139 patients taking anti-platelets post-CABG were included. For preventing SVG occlusion, Asp+Tica showed the lowest mean AR of 0.144±0.068. Asp+Tica also showed a trend toward lesser postoperative MI risk and lower ACM rates, with a mean AR of 0.040±0.053 and 0.018±0.029, respectively. For maintaining IMA graft patency, Asp+Clopi showed the lowest mean AR of 0.092±0.053. Ticagrelor had the lowest mean AR of 0.049±0.075, with Asp+Tica showing a similar mean AR of 0.049±0.045 for postoperative major bleeding risk. Our analysis demonstrates that Asp+Tica can be the ideal therapy for patients undergoing CABG using SVG as it decreases the risk of post-CABG SVG occlusion and is not associated with a significantly higher risk for major bleeding.

The impact of ticagrelor therapy on CABG-related bleeding in patients with STEMI managed with pPCI and following on-pump CABG.

Patients on double antiplatelet treatment who need early in-hospital coronary artery bypass grafting (CABG) are at high risk of major bleeding. In this study, we aimed to investigate the impact of ticagrelor preloading on CABG related bleeding in patients with ST-segment elevation myocardial infarction (STEMI) initially managed with primary percutaneous coronary intervention (pPCI). Patients with the diagnosis of STEMI who were managed with pPCI and underwent subsequent early (4-7days following pPCI) or delayed (> 7days following pPCI) on-pump CABG surgery were included. All study patients were preloaded with ticagrelor 180mg prior to pPCI procedure. Patients' demographics, clinical variables, and short-term cardiovascular outcomes were recorded. This is a retrospective study which included 98 patients. Fifty-four (54%) patients underwent early and 44 (45%) patients underwent delayed CABG surgery. CABG-related bleeding occurred in 22 (22.4%) patients. There was no significant difference with respect to total ticagrelor dose and timing of the surgery between patients with or without CABG-related bleeding (p: 0.165 and p: 0.142). Multivariate analyses demonstrated that only preoperative hemoglobin level < 10.9 and use of mechanical cardiac support devices were independent predictors of CABG-related bleeding [OR: 3719, p: 0.009 and OR: 11,698, p: 0.004, respectively].There were three deaths within the 30days of surgery, all occurring in patients with CABG-related bleeding. However, CABG-related bleeding was not associated with long-term cardiovascular events during the follow-up. Our results indicated that discontinuation of ticagrelor therapy 3days prior to surgery is sufficient to avoid CABG-related bleeding. Moreover, early CABG following STEMI does not increase the risk of long-term cardiovascular events.

Poor patients' knowledge about venous thromboembolism and its therapy is associated with increased risk of major bleeding and discontinuation of anticoagulation: A cohort study.

It has been shown that patients' knowledge about venous thromboembolism (VTE) and its therapy is suboptimal, which might reduce compliance and worsen prognosis. We investigated whether low VTE patients' knowledge affects their clinical outcomes during long-term follow-up. We evaluated 151 consecutive patients (51.8 ± 15.7 years) after unprovoked VTE, who were recruited from the outpatient clinic (Krakow, Poland). All patients received anticoagulant treatment, mostly with direct oral anticoagulants (n = 113, 74.8%). The modified Jessa Atrial fibrillation Knowledge Questionnaire (JAKQ-VTE; 16 questions) was used to assess the knowledge of VTE and anticoagulant therapy. During a median follow-up of 58.0 months, VTE recurrence, major bleeding, and anticoagulation withdrawal were recorded. The median percentage of correct responses was 62.5% (12.5-100%) and was inversely correlated with age (P < .01). Diabetic patients and those with positive family history of VTE had lower overall scoring compared to the remainder (both P < .05). Major bleeding (n = 10, 6.6%) and anticoagulation withdrawal (n = 28, 18.5%), but not VTE recurrence (n = 12, 7.9%), were associated with lower overall scoring compared to the remainder (48.8% ± 12.5% vs 63.8% ± 16.3%, P = .003 and 55.3% ± 14.7% vs 64.4% ± 16.3%, P = .040, respectively). Major bleeding was independently associated with the female sex (hazard ratio [HR] 6.18; 95% confidence interval [CI] 1.15-33.19, P = .034), younger age (HR per 10 years 0.55; 95% CI 0.34-0.90, P = .016), OAC therapy discontinuation (HR 6.69; 95% CI 1.62-27.70), and lower overall scoring of JAKQ-VTE (HR 0.60 per 10 percentage points; 95% CI 0.40-0.92, P = .019). Insufficient knowledge about VTE and anticoagulant treatment predisposes to a higher risk of major bleeding and therapy discontinuation, but not VTE recurrence in unprovoked VTE patients during long-term follow-up.

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.

Platelet-fibrin clot strength and platelet reactivity predicting cardiovascular events after percutaneous coronary interventions.

Platelet-fibrin clot strength (PFCS) is linked to major adverse cardiovascular event (MACE) risk. However, the association between PFCS and platelet reactivity and their prognostic implication remains uncertain in patients undergoing percutaneous coronary intervention (PCI). In PCI-treated patients (n = 2512) from registry data from January 2010 to November 2018 in South Korea, PFCS using thromboelastography and platelet reactivity using VerifyNow were measured. High PFCS (PFCSHigh) was defined as thromboelastography maximal amplitude ≥ 68 mm, and high platelet reactivity (HPR) was defined as >208 P2Y12 reaction units. Patients were stratified into four groups according to maximal amplitude and P2Y12 reaction unit levels: (i) normal platelet reactivity (NPR)-PFCSNormal (31.8%), (ii) HPR-PFCSNormal (29.0%), (iii) NPR-PFCSHigh (18.1%), and (iv) HPR-PFCSHigh (21.1%). Major adverse cardiovascular event (all-cause death, myocardial infarction, or stroke) and major bleeding were followed up to 4 years. High platelet reactivity and PFCSHigh showed an additive effect for clinical outcomes (log-rank test, P < .001). Individuals with NPR-PFCSNormal, NPR-PFCSHigh, HPR-PFCSNormal, and HPR-PFCSHigh demonstrated MACE incidences of 7.5%, 12.6%, 13.4%, and 19.3%, respectively. The HPR-PFCSHigh group showed significantly higher risks of MACE compared with the NPR-PFCSNormal group [adjusted hazard ratio (HRadj) 1.89; 95% confidence interval (CI) 1.23-2.91; P = .004] and the HPR-PFCSNormal group (HRadj 1.60; 95% CI 1.12-2.27; P = .009). Similar results were observed for all-cause death. Compared with HPR-PFCSNormal phenotype, NPR-PFCSNormal phenotype was associated with a higher risk of major bleeding (HRadj 3.12; 95% CI 1.30-7.69; P = .010). In PCI patients, PFCS and platelet reactivity demonstrated important relationships in predicting clinical prognosis. Their combined assessment may enhance post-PCI risk stratification for personalized antithrombotic therapy.

Clinical impact of renal function changes in patients with atrial fibrillation receiving anticoagulation with marginal renal function

Abstract Background Renal function changes were frequently observed in patients with marginal renal function. Renal function is one of crucial components to determine the doses and types of oral anticoagulants in atrial fibrillation (AF) patients and also closely associated with the risk of stroke and bleeding. However, the incidence of renal function changes and its impact on the clinical outcomes were not well-elucidated in anticoagulated AF patients. Purpose To evaluate renal function changes during follow-up in anticoagulated AF patients with marginal renal function defined as estimated glomerular filtration rate (eGFR) 45 to &amp;lt;60 ml/min/1.73m2. We also analysed the association between renal function changes and clinical outcomes. Methods Using a Korean nationwide claims database, we included anticoagulated AF patients who underwent a national health examination from January 2014 to December 2018 and also had follow-up examination within 2-year. Patients with eGFR 45 to &amp;lt;60 ml/min/1.73m2 at baseline examination were included. Based on the follow-up eGFR values, patients were categorised into three groups according to the change in renal function: maintained group (maintaining follow-up eGFR ranges from eGFR 45 to &amp;lt;60 ml/min/1.73m2), improved group (eGFR &amp;gt;60 ml/min/1.73m2), and aggravated group (eGFR &amp;lt;45 ml/min/1.73m2). After follow-up examination, ischemic stroke, major bleeding, end-stage renal disease (ESRD), all-cause death, and the composite of all clinical outcomes were evaluated. Results A total of 5126 patients were included: 42.3 % of patients (n=2170) maintained their renal function at follow-up examination, renal function of 44.4 % of patients (n=2276) were improved, whereas 13.3% of patients (n=680) were aggravated at follow-up examination. The mean eGFR values at baseline of maintained, improved, and aggravated groups were 54.2±4.1, 55.5±3.7, and 52.2±4.3 ml/min/1.73m2, respectively (p&amp;lt;0.001). The aggravated group was older, had higher CHA2DS2-VASc scores, and had more prevalent comorbidities, including hypertension, diabetes, prior myocardial infarction, and heart failure, than other groups. After multivariable adjustment, the aggravated group was associated with significantly higher risks of major bleeding, ESRD, all-cause death, and the composite outcome (HR [95% confidence interval], 1.46 [1.03-2.07], p=0.035; 1.49 [1.24-1.80], p&amp;lt;0.001; 9.29 [4.92-17.6], p&amp;lt;0.001; 1.57 [1.36-1.83], p&amp;lt;0.001, respectively). Conclusion In the anticoagulated AF patients with marginal renal function, a substantial proportion of patients (13%) experienced renal function decline below eGFR 45 ml/min/1.73m2 within 2-year. Renal function decline was associated with higher risks of major bleeding, ESRD, all-cause death and the composite outcome than those maintained their baseline renal function. Performing regular check-ups of renal function and protecting renal function should be emphasised in anticoagulated patients with AF and marginal renal function.