Gastrointestinal Bleeding Research Articles

Impact of digoxin on gastrointestinal bleeding following left ventricular assist device implantation: a systematic review and meta-analysis

Abstract Introduction Gastrointestinal bleeding (GIB) is a common complication post Left Ventricular Assist Device (LVAD) implantation for patients with advanced heart failure. Recent observational evidence suggested a potential association of digoxin use and GIB reduction post LVAD; however, the proposed benefit remains uncertain. Therefore, we conducted a systematic review and meta-analysis to assess the impact of digoxin use on GIB post LVAD. Methods We performed a systematic review and meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched PubMed and EMBASE for the studies published in English exploring GIB with chronic digoxin use following LVAD implantation, till 15/01/2024. Two independent reviewers assessed the quality and risk of bias of the included studies. A random-effect model was used to combine data. The primary outcome was all-cause GIB associated with digoxin use in comparison to non-digoxin use. Heterogeneity was assessed using Q test and I2, with I2 > 50% indicating marked heterogeneity. Results A total of three peer-reviewed observational studies (n= 14277) were included in the analysis of the primary outcome. More than 50% of patients received ACE inhibitors/angiotensin receptor blockers. Digoxin use post LVAD was associated with similar GIB incidence in comparison to non-digoxin use (Odds Ratio [OR]= 0.61; 95% CI, 0.33-1.14, I2= 81%, P=0.12), as shown in Figure 1. Interestingly, one study of 199 recipients of LVAD reported significantly lower gastrointestinal angiodysplasia-induced GIB with digoxin use (3% versus 13%, P=0.039). Conclusion Among patients with advanced HF requiring LVAD implantation, the use of digoxin demonstrated similar effectiveness of GIB prevention compared to non-digoxin use. Future studies needed to explore the potential use of digoxin for gastrointestinal angiodysplasia-induced GIB.Figure 1.Forest plot of gastrointestina

Impact of resumption of Oral AntiCoagulation therapy (OAC) after GastroIntestinal Bleeding (GIB) on clinical outcomes in patients with Non-Valvular Atrial Fibrillation (NVAF)

Abstract Purpose Optimal resumption of oral anticoagulation therapy (OAC) after gastrointestinal bleeding (GIB)has not been well established. This study aimed to compare clinical outcomes between patients who resumed or discontinued OAC after index GIB. Methods We retrospectively enrolled consecutive patients with non-valvular atrial fibrillation (NVAF) and prior GIB from January 2018 to July 2022 in 16 public hospitals in Hong Kong. Resumption of OAC was substantiated by new prescription after index GIB on electronic medical records. Patients were divided into 5 groups: (i) OAC naïve (as reference group); (ii) resume direct oral anticoagulant (DOAC); (iii) resume Vitamin K antagonist (VKA); (iv) discontinue DOAC; (v) discontinue VKA. Endpoints included recurrent GIB, ischemic stroke and all-cause death. Risks of target events were estimated for all groups and compared with individuals without OAC, using adjusted sub-distribution hazard ratios (aSHR) derived from Fine and Gray regression models, accounting for death as competing risk for recurrent GIB and stroke, and COX proportional regression for all-cause mortality, adjusting for components of CHA2DS2VASC, HASBLED scores, causes of index GIB (i.e., GI ulcer, diverticular disease, angiodysplasia or undermined) and endoscopy intervention. Among patients who resumed OAC, outcomes were compared between different DOAC agents (i.e, apixaban, dabigatran, edoxaban, rivaroxaban), using VKA as reference. Results Of 2,350 patients identified (mean age 80.5±10.4, female 54.5%), 44.0% (n=1,034) were OAC naïve, 4.4% (n=103) discontinued VKA, 11.7% (n=275) discontinued DOAC, 11.2% (n=263) resumed VKA, and 28.7% (n=675) resumed DOAC. During a median follow-up duration of 1.2(IQR:0.2-2.5) years, discontinuation of DOAC (aSHR=0.5(0.29-0.9) was associated with lower risk of recurrent GIB, whereas resumption of VKA (aSHR=1.8(1.0-3.1)) was associated with the highest risk of recurrent GIB (Figure 1a). Among DOACs, apixaban (aSHR=0.5(0.3-0.9)) was associated with the lowest risk of recurrent GIB (Figure 1b). Risk of ischemic stroke across groups were similar. Patients who discontinued DOAC (aHR=1.4(1.2-1.6)) were at higher risk of all-cause mortality, whereas resumption of VKA (aHR=0.4(0.3-0.6)) and DOAC (aHR=0.4(0.4-0.5)) were both associated with decreased mortality (Figure 1c). Conclusion In this real-world dataset, resumption of VKA in NVAF patients after GIB was associated with high risk of recurrent GIB and lowest risk with apixaban. OAC resumption either VKA or DOAC was associated with reduced mortality.

Association between reduced risk of gastrointestinal bleeding related to proton pump inhibitor use and subsequent all-cause death in patients with percutaneous coronary intervention

Abstract Background Gastrointestinal bleeding is the leading cause of post-percutaneous coronary intervention (PCI) bleeding complications which are associated with a high risk for subsequent clinical outcomes. The aim of this study was to estimate association between risk of gastrointestinal bleeding events related to proton pump inhibitor (PPI) use and subsequent clinical outcomes in patients with PCI. Methods The Clinical Deep Data Accumulation System (CLIDAS) is a database for inclusive of patient characteristics, medications, laboratory test, physiological test, cardiac catheterization and PCI treatment, all of which were aggregated from electronic medical records in 7 tertiary hospitals in Japan. Data of 6457 patients who underwent PCI between April 2014 and March 2020 and were then followed for 30 days after the index PCI, were analyzed. These patients were divided into two groups based on use of PPI; the PPI group (n=5285; 82%) and the non-PPI group (n=1172; 18%). Clinical outcomes, defined as gastrointestinal bleeding and all-cause death, were assessed using propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) models. Results Among the 6457 PCI patients, 90 (1.7%) in the PPI group and 31 (2.6%) in the non-PPI group experienced gastrointestinal bleeding events. Adjusting for baseline demographics, comorbidities, and anti-thrombotic treatments, the multivariable Cox hazard model suggested a trend towards a lower risk of gastrointestinal bleeding with PPI use (HR, 0.70; 95%CI, 0.46-1.05; p=0.087). The PSM analysis confirmed a significant association between PPI use and a lower risk of gastrointestinal bleeding (HR, 0.13; 95%CI, 0.04-0.43; p=0.001), consistent with IPTW model results (HR, 0.60; 95%CI, 0.38-0.95; p=0.031). Subgroup analysis showed that PPI use was associated with a low risk of all-cause death in patients with acute coronary syndrome (ACS) (HR, 0.58; 95%CI, 0.36-0.93; p=0.024). Causal mediation analysis indicated an indirect effect of PPI on reducing all-cause death through the suppression of gastrointestinal bleeding events. Conclusion These findings suggested that use of PPI against gastrointestinal bleeding complications might reduce the risk of subsequent all-cause death in ACS patients undergoing PCI.

Prior fecal immunochemical test positivity is associated with adverse prognosis in patients with acute ST-segment elevation myocardial infarction

Abstract Backgrounds While fecal immunochemical testing (FIT) is commonly used for disease screening, its significance in other conditions, particularly in patients with ST-segment elevation myocardial infarction (STEMI), is not extensively researched. Purpose This study aimed to investigate the impact of prior positive FIT results on the clinical prognosis of patients with STEMI. Methods The data for this study were derived from the Health and Medical Big Data Superplatform, comprising a retrospective cohort of patients discharged from 72 hospitals from 2010 to 2023. A total of 76,157 patients with acute STEMI patients were enrolled. Positive FIT was defined as "+-" or higher on the fecal occult blood test. Propensity score matching (PSM) was employed to balance differences between the two groups. Kaplan-Meier analysis with log-rank tests compared endpoint risks between groups, and a multivariable Cox regression model adjusted for potential confounders. The primary endpoint was Net Adverse Clinical Event (NACE), including cardiac death, recurrent myocardial infarction, revascularization, stroke, cerebral hemorrhage, and gastrointestinal bleeding. Results After 1:3 PSM,2,148acute STEMI patients were included, with 537 having prior positive FIT and 1,611 without. Patients with prior positive FIT were more likely to have comorbidities such as hyperlipidemia, prior malignancy, post-coronary artery bypass grafting, renal insufficiency, and prior cerebral hemorrhage. The prior positive FIT group had a higher proportion of prior clopidogrel and indobufen usage, while aspirin use during follow-up was lower. Kaplan-Meier analysis demonstrated a significantly higher risk of NACE in acute STEMI patients with prior positive FIT (before PSM: log-rank P = 0.001, after PSM: log-rank P = 0.005, Figure 1）, as well as increased rates of Major Adverse Cardiac and Cerebral Events (MACCE), all-cause death, and gastrointestinal bleeding (log-rank P < 0.05 for all). Multivariate Cox-proportional hazard analysis adjusted for age, sex, percutaneous coronary intervention during hospitalization, diabetes, hypertension, ischemic stroke, atrial fibrillation, medication during hospitalization, and follow-up showed similar results (Figure 2). Conclusions This study reveals a significant association between prior positive FIT and higher rates of NACE, MACCE, all-cause death, and gastrointestinal bleeding in STEMI patients within 1 year. A history of positive FIT results could serve as a prognostic indicator in this specific patient population.

Risk of thromboembolic and haemorrhagic events associated with anticoagulation among 11,355 patients with non-valvular atrial fibrillation and thrombocytopenia

Abstract Background Oral anticoagulation (OAC) is the mainstay for stroke prophylaxis in patients with non-valvular atrial fibrillation (NVAF). Management is challenging among patients with NVAF complicated with thrombocytopenia. Purpose We compared risk of thromboembolic and hemorrhagic events between vitamin-k antagonist (VKA) and direct oral anticoagulants (DOAC) users. Methods We retrospectively analyzed patients with thrombocytopenia and NVAF prescribed VKA (N=5,251, 46.2%) and DOAC (N=6,104, 53.8%) between January 2012 and July 2022 in 16 public hospitals in Hong Kong. Mild to moderate thrombocytopenia was defined as mean platelet count (PLT) 100-150 × 10^9/L and 50-100 × 10^9/L respectively, during the year of OAC initiation. Propensity-matched cohorts of VKA and DOAC were generated on the basis of age, sex, baseline co-morbidities (components of CHA2DS2VASC and HAS-BLED scores) and medications. Time to intracranial hemorrhage (ICH), gastrointestinal bleeding (GIB) and ischemic stroke (IS) was analyzed using competing risk regression, accounting for death as competing risk. Subgroup analysis was performed to detect heterogeneity of effect across mild and moderate thrombocytopenia. Secondary outcome included (i) comparisons between 4 DOAC agents with full dose; (ii) Full-dose DOAC vs. reduced-dose DOAC. Results Of the whole cohort (N=11,355, mean age 75.8±10.5, female 38.6%), 10.3% (n=1,174) and 89.7% (n=10,181) had moderate and mild thrombocytopenia, respectively. After propensity-score matching, VKA and DOAC (n=4,302 each cohort) users were well balanced at baseline characteristics, with a median follow-up of 4.0 (IQR: 1.6-7.3) years. Overall, utilization of DOAC was associated with reduced risk of ICH [Hazards Ratio (HR) 0.56 (95% CI 0.45-0.70)] and GIB [HR 0.60 (95% CI 0.48-0.75)], compared with VKA. No difference in risk of IS was observed [HR 1.00 (95%CI 0.83-1.20)]. Dosing reduction of DOAC made no difference in all outcomes. Subgroup analysis demonstrated the benefit in decreasing GIB might be more marked in moderate thrombocytopenia [(HR 0.24 (95%CI 0.09-0.61)], than in mild thrombocytopenia [HR 0.64 (95%CI 0.51-0.81)]. Conclusion In patients with NVAF and thrombocytopenia, DOAC has similar efficacy but better safety profile than VKA. In terms of GIB, the superiority appeared to be more pronounced in patients with more significant thrombocytopenia.

Direct oral anticoagulants exhibit lower risks of mortality and bleeding compared to vitamin-k antagonists in atrial fibrillation patients on chronic hemodialysis: a meta-analysis

Abstract Background Atrial fibrillation (AF) is a common arrhythmia in patients with chronic kidney disease (CKD). Although direct oral anticoagulants (DOACs) are equally or more effective than vitamin K antagonists (VKAs) in patients with moderate CKD, evidence claiming the benefits of DOACs over VKAs in patients on hemodialysis (HD) is scarce. Purpose This meta-analysis aimed to assess the outcomes of patients with AF on chronic HD by comparing the clinical outcomes of DOACs versus VKAs. Methods A systematic literature search was conducted across various databases to retrieve studies focusing on efficacy and safety outcomes in patients with AF on chronic hemodialysis comparing DOACs and VKAs. Relative risks (RRs) with 95% confidence intervals (CIs) were pooled using the Mantel-Haenszel random-effects model in Review Manager 5.4. Statistical significance was set at p <0.05. Results Nine studies with 39, 831 patients were included. The risk of all-cause mortality [RR: 0.73; 95% CI: 0.60, 0.88; p=0.001], major bleeding [RR: 0.63; 95% CI: 0.52, 0.76; p<0.00001], gastrointestinal bleeding [RR: 0.67; 95% CI: 0.53, 0.85; p=0.0009], intracranial hemorrhage [RR: 0.57; 95% CI: 0.38, 0.84; p=0.004], all-cause stroke [RR: 0.64; 95% CI: 0.51, 0.81; p=0.0001], and ischemic stroke [RR: 0.53; 95% CI: 0.29, 0.96; p=0.04] were lower in the DOAC group than in the VKA group. The risk of cardiovascular-related death [RR: 1.34; 95% CI: 0.69, 2.60; p=0.39], and clinically relevant non-major bleeding [RR: 0.90; 95% CI: 0.75, 1.08; p=0.26] showed no significant differences. Conclusion The risks of all-cause stroke, ischemic stroke, all-cause mortality, major bleeding, gastrointestinal bleeding, and intracranial hemorrhage in the patients with AF undergoing chronic HD were lower in the DOAC group than in the VKA group. Further large-scale RCTs are needed to generate more robust evidence through adequately powered studies, leading to conclusive results that are applicable to real-world scenarios.

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

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

Complication comparison in intermediate-to-high risk venous thromboembolism patients, treated with high vs standard dose apixaban and rivaroxaban after low molecular weight heparin

Abstract Background In patients with intermediate-to-high risk venous thromboembolism (VTE), current guidelines recommend initial treatment with low molecular weight heparin (LMWH), followed by an oral anticoagulant. However, the studies supporting these guidelines have only focused on the use of Edoxaban and Dabigatran after 5 days of LMWH treatment. To date there are no studies supporting similarly implemented guidelines for Apixaban and Rivaroxaban. Purpose To investigate the incidence of bleeding complications and thrombosis in intermediate-to-high risk VTE patients, when treated with either lead-in high or standard dose Rivaroxaban or Apixaban, following initial LMWH treatment. Methods Through a real-life retrospective study of 844 intermediate-to-high risk VTE patients, 584 were initially treated with LMWH and subsequently Apixaban or Rivaroxaban and divided into two groups. The first group of 514 patients, received high dose Apixaban or Rivaroxaban (10mg x 2 for 7 days and 15mg x 2 for 21 days respectively) before being reduced to their standard doses. The remaining 70 patients, instead transitioned directly to the standard doses (5mg x 2 and 20mg x 1 respectively) from LMWH. All patients started treatment between 2018 and 2023, and all complications were recorded until one year following initiation of treatment. Treatment complications include recurrent VTE, separated into deep vein thrombosis and pulmonary embolism, and bleeding complications in the form of fatal, non-fatal, minor and a drop in haemoglobin. The recurrence of VTE and incidence of bleeding complications were evaluated as the primary efficacy outcome and safety outcome respectively. Results Overall, 4.7% of patients treated with initial high dose Apixaban or Rivaroxaban suffered major bleeding complications as opposed to 2.9% treated with the standard dose (p=<0.05). Out of all complications, 5 were fatal, all of which were part of the high dose group and included 3 cerebral and 2 gastrointestinal bleeds. However, minor bleeding complications were more frequent in the standard dose group, presenting in 26.1% of patients, while, paradoxically, the high dose group had similar complications in only 15.8% of patients (p=<0.05). Although treated with a higher dose, 6/478 (1,26%) incurred a recurrent thrombus within a year of treatment, while the standard dose group had no cases of recurrence, though this was not a statistically significant result. Conclusion Directly transitioning from LMWH to standard dose Apixaban/Rivaroxaban in intermediate-to-high risk VTE, leads to a statistically significant reduced incidence of major bleeding complications, without an increased risk of recurrent thrombosis.

Antiplatelet agents in patients with intermediate coronary artery stenosis and deferred revascularization

Abstract Background There is no specific recommendation regarding optimal antiplatelet therapy after deferral of revascularization in patients with established coronary artery disease. Objectives The current study investigated safety and efficacy of antiplatelet therapy in patients with intermediate coronary artery stenosis in whom revascularization was deferred based on fractional flow reserve (FFR). Methods In the Korean National Health Insurance Service database 2013-2020, we identified 4,657 patients who had intermediate coronary artery disease on angiography for which revascularization was deferred based on FFR. During this period, reimbursement criteria of FFR were patients with no previous evidence of myocardial ischemia and intermediate coronary artery stenosis (50-70%) by quantitative coronary angiography. Patients were then classified into two groups according to initiation of antiplatelet therapy after the index procedure. Primary efficacy outcome was major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause death, myocardial infarction, unplanned revascularization, and stroke, during 5 years of follow-up. Primary safety outcome was any gastrointestinal bleeding. Results After propensity score matching in a 1:1 ratio, there were 1,634 patients in antiplatelet therapy group and 1,634 in no therapy group (total N=3,268). The risk of MACCE was similar between the two groups (24.8% vs. 24.7%; adjusted hazard ratio [aHR], 0.97; 95% confidence interval [CI], 0.84-1.13; P=0.745). However, the risk of any gastrointestinal bleeding was higher in antiplatelet therapy group than no therapy group (2.2% vs. 1.2%; aHR, 2.07, 95% CI, 1.08-4.00). These results were consistently found in subgroup analyses. Conclusions In patients with intermediate coronary artery stenosis with deferred revascularization based on FFR, antiplatelet therapy was not associated with reduced risk of ischemic events but increased risk of gastrointestinal bleeding.

G-CSF-In Patients With Severe Alcohol-Associated Hepatitis: A Real-World Experience.

Severe alcohol-associated hepatitis (SAH) is associated with high short-term mortality, and failure of response to corticosteroids is associated with a mortality of ~70%-80% within 6 months. Granulocyte colony-stimulating factor (G-CSF) has been studied in steroid non-responders; however, the data are limited. This is a multicentre retrospective cohort study. The study period was from January 2016 to November 2023. SAH was defined as alcohol-associated hepatitis (ICD-10-CM codes) with serum bilirubin ≥ 5.0 mg/dL and INR ≥ 1.5. Other aetiologies of acute hepatitis and biliary obstruction were excluded. The primary outcome was 90-day median overall survival in SAH patients treated with G-CSF compared with standard medical therapy (SMT) or corticosteroids. Propensity score (1:1) matching was performed to control confounding variables. Among 20 132 patients with SAH, 10800 (53.65%) were treated with corticosteroids and 224 (1.11%) G-CSF. The G-CSF group was younger (45.5 vs. 48.4) White (79.91% vs. 72.40%); however, there was no age or gender difference between G-CSF and corticosteroid groups. Whites and patients with more comorbidities received G-CSF more frequently than SMT or corticosteroids. After propensity score matching, 90-day overall survival was better in patients who received G-CSF (88.31% vs. 62.36%, p < 0.01) compared with SMT or corticosteroids (88.31% vs. 74.39%, p < 0.01). Patients on G-CSF had better 6-month transplant-free survival compared with SMT (83.53% vs. 55.36%, p < 0.001) or corticosteroids (82.89% vs. 60.21%, p < 0.001). Gastrointestinal bleeding was less common in G-CSF group compared with corticosteroids (5.02% vs. 10.50%, p < 0.001). A small minority of patients with severe alcohol-associated hepatitis receive G-CSF. G-CSF improves 90-day overall survival in patients with severe alcohol-associated hepatitis and is non-inferior to corticosteroids.

The efficacy and safety of NOAC in very elderly atrial fibrillation patients; data from the Korean national health insurance cohort registry

Abstract Background Data regarding efficacy and safety on anticoagulation in very elderly atrial fibrillation patients are relatively sparse. Purpose We investigated the clinical benefit of anticoagulation with NOAC in very elderly AF patients through national healthcare insurance registry. Methods Clinical data of 862,935 patients who were diagnosed with AF from 2015 to 2020 were collected for analysis. Patients under the age of 85, prior history of ICH, GI bleeding and prior prescription days of aspirin, warfarin and NOAC exceeding 90 along with follow up period less than 90 days were excluded. Results A total of 10,625 patients were eligible for analysis. Patients with OAC (HR: 0.60, 95% CI 0.53-0.69), p&amp;lt;0.001) showed higher efficacy regarding systemic embolism compared to aspirin (HR: 0.84, 95% CI 0.74-0.95, p=0.008) and no treatment group. Individual comparison of NOAC and aspirin via propensity score matching showed that patients with NOAC (HR: 0.71, 95% CI 0.61-0.85), p&amp;lt;0.001) showed higher event free survival regarding systemic embolism compared to aspirin. Bleeding risk was also higher for NOAC (HR: 1.28, 95% CI 1.07-1.56, p=0.006) group but did not result in commensurate increase in mortality (HR:0.60, 95% CI 0.45-0.81, p&amp;lt;0.001). Conclusions Anticoagulation with NOAC in very elderly patient showed higher event free survival regarding systemic embolism. Despite having higher event rate of bleeding, eventual death did not show any association with NOAC.

Clinical outcomes in &amp;gt;10,000 Asian vs &amp;gt;61,000 Non-Asian race patients with AF randomized to Warfarin vs DOACs: a patient-level meta-analyses from COMBINE AF

Abstract Background Randomized data comparing clinical outcomes of atrial fibrillation (AF) patients with Asian vs non-Asian races are limited. Methods Using the COMBINE AF (A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation) database (data from RE-LY, ROCKET AF, ARISTOTLE, and ENGAGE AF-TIMI 48), we performed an individual patient-level meta-analysis to investigate and compare clinical outcomes of AF patients with self-defined Asian and non-Asian races adjusted for baseline characteristics. Standard-dose direct oral anticoagulants (SD DOAC) were defined as dabigatran 150mg bid; rivaroxaban 20mg (15mg) QD, apixaban 5 mg (2.5 mg) bid, or edoxaban 60 mg (30 mg) QD. Low-dose DOACs (DOACs [LD]) were defined as dabigatran 110 mg bid or edoxaban 30 mg (15mg) QD. Results There were 10,212 pts of Asian race and 61,471 non-Asian races in the COMBINE AF database. Compared with non-Asians, Asians were on average 3.2 yrs younger, 20 kg lighter, had worse renal function (mean CrCl 64.9 vs. 77.3 mL/min), and higher rates of prior stroke/transient ischemic attack (37.2% vs 26.6%), P&amp;lt;0.001 for each. The median value of time in therapeutic range of patients randomized to warfarin was lower in Asians than non-Asians (57.7% vs. 66.2%, P&amp;lt;0.001). In the warfarin arm, Asians had a higher adjusted risk of stroke/systemic embolic events (SEE), major bleeding (MB), ICH, GI bleeding (GIB), and net clinical outcome (NCO: stroke/SEE, MB, or death)(Figure; Upper panel). Compared to warfarin, SD DOACs significantly reduced the risks of stroke/SEE, MB, and NCO to a greater degree in Asians than non-Asians (HR stroke/SEE: Asians 0.65 vs Non-Asians 0.86; HR MB: Asians 0.62 vs Non-Asians 0.91; HR NCO: Asians 0.76 vs non-Asians 0.94; Pint &amp;lt;0.02 for each), while SD DOACs increased GIB only in non-Asians (Asian HR 0.92 [0.69-1.23] vs Non-Asians HR 1.41 [1.25-1.58], Pint 0.009; Figure Lower panel). Conclusions The adjusted risks of stroke/SEE and major bleeding with warfarin were higher in Asians compared to non-Asians. The benefits of DOACs over warfarin in preventing stroke/SEE, MB, and net clinical outcomes were significantly greater in Asians than non-Asians.

The real-world safety of ticagrelor among older adults (above 75 years): a pharmacovigilance study from the FDA data

Abstract Introduction Potent P2Y12 inhibitors are recommended in conjunction with Aspirin for the treatment of acute coronary syndrome. Since Prasugrel is relatively contraindicated in patients older than 75 years, Ticagrelor remains the primary potent P2Y12 inhibitor option for this age group. However, its safety profile among older adults has not been adequately examined. Purpose To examine Ticagrelor safety profile among older adults (≥75 years) patients Methods We conducted a retrospective pharmacovigilance study utilizing the FDA Adverse Event Reporting System (FAERS) database. We employed disproportionality analysis comparing Ticagrelor to Clopidogrel. We evaluated the reporting of predefined adverse events (dyspnea, bradyarrhythmia, complete AV block [CAVB], intracranial hemorrhage, gastrointestinal hemorrhage, acute kidney injury [AKI], and gout) in adults (&amp;lt;75 years) and older adults (≥75 years). For each group, we calculated reporting odds ratio (ROR) and its 95% confidence interval and compared them by calculating P for interaction. Results The FAERS database encompassed 6,476 adverse event reports for Ticagrelor; 4,795 (74%) adults and 1,681 (26%) older adults. Among older adults and compared to Clopidogrel, Ticagrelor was not associated with an increased reporting for dyspnea (ROR 3.3 [2.7-3.9] vs. 3.9 [3.5-4.5]), bradyarrhythmia (ROR 4.1 [2.5 – 6.7] vs 5.4 [3.9 – 7.6]) intracranial hemorrhage (ROR 1.1 [0.7-1.7] vs. 1.1[0.8-1.5]), CAVB (ROR 11.5 [3.1–42.4] vs. ROR 27.8 [6.7-116.3]), and gout (ROR 3.8 [0.5-27] vs. 3.9 [2-7.5]). AKI was reported more frequently among older adults (ROR 2.3 [1.5-3.6] vs. 0.6 [0.4-0.9]). Ticagrelor was not associated with an increased reporting of GI hemorrhage. Conclusion According to the FAERS, Ticagrelor is generally safe for use in older adults (≥75 years) with no significant increase in the reporting of major adverse events compared to adults (&amp;lt;75 years), except for a higher reporting of AKI.

Evaluation of the biomarker-based ABC-AF-bleeding risk score and clinically based bleeding scores in 31,605 patients with atrial fibrillation treated with oral anticoagulation

Abstract Background International guidelines recommend a systematic evaluation of bleeding risk in patients with atrial fibrillation (AF) to guide oral anticoagulation. However, it remains challenging to accurately predict bleeding risk. The biomarker-based ABC-AF-bleeding risk score to predict bleeding in anticoagulated patients with AF has shown promise. Purpose To evaluate the performance of the biomarker-based ABC-AF-bleeding risk score and compare its performance with other bleeding risk scores in 31,605 patients randomized to direct oral anticoagulant or warfarin using individual patient data from three randomized clinical trials. Methods The COMBINE AF biomarker data set contains individual patient data from three pivotal randomized trials (ARISTOTLE, ENGAGE AF-TIMI 48, and RE-LY) comparing apixaban, edoxaban or dabigatran with warfarin, in patients with AF at increased risk of stroke. The ABC-AF-bleeding biomarkers were analyzed in plasma samples collected at baseline (hemoglobin, troponin T high-sensitivity, and GDF-15) using Roche Diagnostics Elecsys assays. The biomarker-based ABC-AF-bleeding risk score (Age, Biomarkers, Clinical history of prior bleeding) was calculated as previously published. The discrimination was assessed by Harrell’s c index and compared with three clinically based bleeding risk scores; HASBLED, ORBIT, and DOAC. Results During a median follow-up time of 2.0 years, a total of 1,572 ISTH major bleeding events occurred (incidence rate per 100 person-years of 2.79) including 593 gastrointestinal (1.04) and 270 intracranial (0.47) bleeding events. The biomarker-based ABC-AF-bleeding score was well calibrated for major bleeding in the total material (Figure). The c indices for major bleeding were 0.68 (95% confidence interval 0.67-0.70), for gastrointestinal bleeding 0.70 (0.68-0.72), and for intracranial bleeding 0.66 (0.63-0.69). The biomarker-based ABC-AF-bleeding risk score provided superior discrimination compared with the clinically based risk scores in the full cohort (Table). The ABC-AF-bleeding risk score also provided superior discrimination for major bleeding in clinically relevant subgroups based on age, sex, body mass index, coronary artery disease, diabetes, heart failure, kidney function, and irrespective of DOAC or VKA use. Conclusions In patients with AF treated with different types of OAC the biomarker-based ABC-AF-bleeding score provide better discrimination of the risk för major bleeding than risk scores based only on clinical factors. The results were consistent for different types of bleeding and across multiple subgroups. There was good calibration when comparing predicted vs observed rate of major bleeding. These findings support the utility of the biomarker-based ABC-AF-bleeding risk score for advancing precision medicine in patients with AF.Calibration of ABC-AF-bleeding scoreTable

Rationale and study design of the international randomized control trial MYocarditis THerapy with Steroids: the MYTHS trial

Abstract Background Immunosuppression is generally suggested in patients with specific subtypes of acute myocarditis, such as eosinophilic myocarditis or giant cell myocarditis or associated with systemic autoimmune disorders. In contrast, no specific treatment for most acute myocarditis complicated by acute heart failure (HF) or cardiogenic shock is recommended beyond the management of acute HF and supportive therapy. Nevertheless, large registries commonly reported using corticosteroids in severe forms without data supporting this strategy. Purpose To assess the safety and efficacy of high-dose pulse intravenous (IV) corticosteroid therapy to treat patients with complicated/fulminant acute myocarditis based on clinical suspicion. Methods An international pragmatic investigator-initiated single-blinded randomized controlled trial that screens patients between 18 and 70 years admitted to the hospital for suspected acute myocarditis (cardiac symptoms onset within three weeks) complicated by acute HF/cardiogenic shock and left ventricular (LV) ejection fraction&amp;lt;41% without significant LV dilation is ongoing. Patients are randomized in a 1:1 ratio to pulsed IV methylprednisolone (1 g) in saline solution (250 mL) daily for three days or placebo (saline without methylprednisolone) on top of standard therapy and maximal supportive care. A final diagnosis of myocarditis is confirmed by histology or cardiac magnetic resonance imaging. A population of 288 patients has been planned to assess a reduction in the probability of reaching the primary endpoint from 25% in the placebo arm to 12% in the methylprednisolone arm with a power of 0.80 (Figure). The main analysis will be conducted on an intention-to-treat basis. Results The primary efficacy endpoint of the trial is defined as the time from randomization to the first event occurring within 6 months, including all-cause death, heart transplantation, or long-term LV assist device implant, or need for an upgrading of the temporary mechanical circulatory support (t-MCS), or ventricular tachycardia (VT)/fibrillation (VF) treated with direct current (DC) shock, or first rehospitalization due to HF or VT/VF, or advanced atrioventricular block. The safety endpoints include a composite of potential complications that can occur, including serious infections, acute gastrointestinal bleeding, and other complications that can be related to corticosteroid therapy or prolonged stay on t-MCS. There are 32 active centers, and 48 patients have been randomized since December 2021. The trial is expected to be completed by the end of 2028. Conclusion The results of the MYTHS trial can define the role of IV methylprednisolone in the initial treatment of patients with complicated forms of acute myocarditis that currently have an unacceptably high mortality rate.

GLASGOW-BLATCHFORD AND ROCKALL SCORE UTILITY IN PREDICTING FINDINGS ON VIDEO CAPSULE ENDOSCOPY IN PATIENTS ADMITTED WITH OVERT SMALL BOWEL BLEEDING

Background and Aims Glasgow-Blachford (GBS) and Rockall scores are recognised tools to prioritize patients with upper gastrointestinal bleeding. Its utility in predicting findings on capsule endoscopy (CE) in patients with overt small bowel bleeding (OSBB) remains unclear. The aim was to assess the use of these scores in predicting relevant findings on CE and outcome among patients with suspected OSBB. Methods Retrospective analysis from January 2019 to June 2022. Clinical parameters and scores were collected at presentation and at 24 hours. Univariate analysis used simple logistic regression, chi-squared test or Mann-Whitney as needed. ROC analysis was performed selecting the optimal cut-off point maximized by the Youden index. Results 79 patients were included. 62% had relevant findings. The predictor showing the highest discrimination ability was the Initial GBS (AUC 0.625 95%CI 0.49 – 0.76). The optimal cut-off point was at least 4, with a sensitivity 98%, specificity 30% and accuracy 72%. Multivariable regression analysis showed inpatient status on CE (OR 117.27; CI 11.32 – 4492.93; p=0.001), shorter time to CE (OR 1.02; CI 1.01 – 1.04 p=0.018), higher initial GBS (OR 1.22; CI 1.06 – 1.43 p=0.009) and higher GBS within 24 hours (OR 1.19; CI 1.04 – 1.37 p= 0.013) were predictive factors for relevant findings on CE, with a model AUC 0.802, Sensitivity 91.8% and Specificity 63.3%. Conclusions GBS and Rockall score were useful in predicting relevant findings on CE in this cohort of patients with suspected OSBB. In patients with GBS 5 or higher, an early CE during the same admission, is warranted.

Predictive value of a noninvasive serological model for disease outcomes in patients with acute upper gastrointestinal bleeding

Predictive value of a noninvasive serological model for disease outcomes in patients with acute upper gastrointestinal bleeding

Adverse event profile of albumin-bound paclitaxel: a real-world pharmacovigilance analysis

BackgroundAbraxane plays a crucial role in the treatment of various types of cancer, despite the considerable attention it has garnered for its adverse drug events (ADEs). Nevertheless, there is currently a significant lack of comprehensive real-world pharmacovigilance studies on the ADEs associated with Abraxane.MethodsWe conducted a retrospective analysis of ADEs associated with Abraxane using data mining from the FAERS database, analyzing data from 2005 to 2023. In a real-world setting, we quantified and visualized the signals of these ADEs using four pharmacovigilance algorithms.ResultsThe FAERS database identified a total of 10,230 adverse event reports associated with Abraxane. The study revealed that Abraxane-related adverse drug events involved 27 system organ classes (SOC), with the strongest signals associated with the lymphatic and hematological systems and hepatobiliary disorders. Additionally, we identified 70 significant Preferred Terms (PT) signals, which included some critical adverse events not highlighted in the product labeling, such as cystoid macular edema. Further analysis of the timing of adverse reactions showed a median onset time of 41 days. Most adverse events (AEs) occurred within the first month of using Abraxane (43.5%), although some were still possible 1 year after treatment (3.5%). Gender-specific analysis indicated that high-risk AEs differed between females (nausea, vomiting, and erythema) and males (febrile neutropenia, disseminated intravascular coagulation, and upper gastrointestinal bleeding).ConclusionThe examined results provide crucial recommendations for optimizing the administration of Abraxane, enhancing its effectiveness, and mitigating potential adverse effects. This knowledge will substantially facilitate the implementation of the substance in clinical settings.

Empiric embolization by vasospasm therapy for acute lower gastrointestinal bleeding: a preliminary report

To report the preliminary result of empiric embolization for angiographycally-negative lower gastrointestinal bleeding (LGIB) by using the pharmaco-induced vasospasm technique with or without the adjunctive use of intra-arterial multi-detector computed tomography (MDCT). 23 LGIB patients with positive MDCT findings but negative angiographic results underwent empiric pharmaco-induced vasospasm therapy. The presumed bleeding artery was semi-selectively catheterized, and a segment of bowel was temporarily spasmed with bolus injection of epinephrine and immediately followed by 4-h’ vasopressin infusion. The rebleeding, primary and overall clinical success rates were reported. MDCT showed 19 bleeders in the SMA territory and 4 bleeders in the IMA territory. Early rebleeding was found in 6 patients (26.1%): 2 local rebleeding, 3 from new-foci bleeding and 1 uncertain. Of the 10 small bowel bleeding patients, only 1 out of the 7 who underwent intra-arterial MDCT showed rebleeding, whereas 2 out of the 3 without intra-arterial MDCT rebled. No patients exhibited procedure-related major complications, including bowel ischemia and cardiopulmonary distress. The overall clinical success rate was 91.3% (21/23) with a 30-day mortality rate of 26.1% (2 of the 6 patients had early rebleeding). Empiric pharmaco-induced vasospasm therapy, when localized with/without adjunctive intra-arterial MDCT, seems to be a safe and effective method to treat angiographically-negative LGIB patients.

Clinical impact of performing esophagogastroduodenoscopy before percutaneous coronary intervention in patients with acute coronary syndrome patients and anaemia

Abstract Background In patients presenting with acute coronary syndrome (ACS) and anaemia, esophagogastroduodenoscopy (EGD) is commonly performed to exclude an upper gastrointestinal source of bleeding prior to perform percutaneous coronary intervention (PCI). However, the diagnostic yield and clinical impact of EGD in this setting is uncertain. Purpose We aimed to investigate the clinical yield and impacts of EGD on the 1-year clinical outcomes in ACS patients with concomitant anaemia who underwent PCI. Methods We retrospectively analysed electronic health records of ACS patients who underwent PCI at 16 public hospitals from 2014-2018. Patients with anaemia (defined as haemoglobin (Hb) &amp;lt;11dl/L) and EGD before PCI during the same admission were identified. The primary outcomes were bleeding events including clinical GIB (as diagnosed by EGD), need for urgent EGD, need for transfusion, Hb drop of &amp;gt;3 dl/L and Hb &amp;lt;8 dl/L. Secondary outcomes were 12-month 4-point MACE including myocardial infarction (MI), stroke, subsequent PCI or CABG, or cardiovascular-related death. Propensity-score models with inverse probability of treatment weighting (IPTW) against EGD were developed for the comparisons. A weighted Cox Proportional Hazard Model was performed to estimate adjusted hazards ratio (aHR) with corresponding 95% confidence intervals (CI). Results Of 13,793 patients, 3625 (25%) had anaemia on admission and 12.8% (n=466/3625) underwent EGD. Most EGD findings were not accountable for overt GIB, with gastritis, gastric polyps and gastric erosion being the 3 most common EGD diagnoses. After IPTW, clinical outcomes of 466 patients with EGD were compared with 3159 patients without EGD. 12-month bleeding event rates were higher among EGD patients compared to non-EGD patients (59.7% vs. 27.6%, p&amp;lt; 0.01; aHR = 3.01, 95% CI 2.58-3.52, p&amp;lt;0.005). Overall, 12-month GIB rate was low 1.0%, with 4.1% in EGD patients and 0.57% in non-EGD patients (aHR=7.99, 95% CI 4.13-15.45, p&amp;lt;0.005). The 12-month cumulative MACE rate overall was 39.9% and no significant difference between EGD and non-EGD patients. Conclusion Our real-world data demonstrated that the presence of anaemia is common among ACS patients. The yield of EGD in identifying sources of upper GI bleeding was low and there was no difference in 12-month clinical outcome among EGD patients. Although EGD was associated with higher rates of 12-month bleeding events, the cause was unclear with very low incidence of upper GI bleeding events. Therefore, the benefits of routine EGD prior to PCI in ACS patients with anaemic is unclear.