Risk Of Gastrointestinal Bleeding Research Articles

Bleeding Associated With Antiarrhythmic Drugs in Patients With Atrial Fibrillation Using Direct Oral Anticoagulants: A Nationwide Population Cohort Study.

This study investigated drug-drug interactions in patients with atrial fibrillation taking both a direct oral anticoagulant (DOAC) and an antiarrhythmic drug. Using data from the National Health Insurance database (2012-2018), we identified 78 805 patients with atrial fibrillation on DOACs, with 24 142 taking amiodarone, 8631 taking propafenone, 2784 taking dronedarone, 297 taking flecainide, 177 taking sotalol, and 42 772 on DOACs alone. Patients with bradycardia, heart block, heart failure, mitral stenosis, prosthetic valves, or incomplete data were excluded. Propensity score matching compared those taking both DOACs and antiarrhythmic drugs with those on DOACs alone. There was an increased risk of major bleeding in patients concomitantly taking DOACs with amiodarone when compared with matched patients taking DOACs alone (hazard ratio [HR],1.13 [95% CI, 1.04-1.23]; P=0.0044), particularly in patients taking dabigatran (HR, 1.19 [95% CI, 1.03-1.38]; P=0.0175). No significant difference in bleeding risk was found for propafenone, dronedarone, flecainide, or sotalol. The small sample sizes in the flecainide and sotalol groups limit interpretation. Notably, intracranial bleeding risk was higher in patients on DOACs and amiodarone, regardless of age. Additionally, patients <80 years old taking dabigatran with amiodarone or propafenone had a higher risk of gastrointestinal bleeding. Concomitant use of DOACs with amiodarone, but not dronedarone or propafenone, increases the risk of major bleeding, particularly intracranial bleeding. This study provides new evidence to guide clinicians to tailor concomitant anticoagulation and antiarrhythmic therapy for patients with atrial fibrillation.

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.

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.

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 &amp;lt;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&amp;lt;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.

Impact of statins on incidence of gastrointestinal bleeding events among patients with continuous-flow left ventricular assist devices.

Patients with continuous flow left ventricular assist devices (CF-LVADs) are at increased risk of gastrointestinal bleeding (GIB). Statins are commonly prescribed in LVAD patients for cardiovascular disease prevention. However, their impact on GIB events is controversial. Importantly, literature regarding statins impact on GIB in CF-LVAD patients is lacking. A single-center, retrospective review of adult patients who underwent CF-LVAD implantation between May 2016 and January 2020 was performed. Patients were categorized based on statin use throughout the study period. The primary outcome was the composite of arteriovenous malformation confirmed GIB and major GIB events for up to 1-year post-LVAD implantation. Of 123 patients included in the final analysis, 66 (54%) received statin therapy during the study period. No difference was observed in the primary outcome between the statin and control groups (RR: 1.73; 95% CI: 0.75-3.98; p=0.20). Multivariable Cox regression revealed that older age and higher baseline creatinine were associated with an increased risk of GIB within 1-year of CF-LVAD implantation. Among patients with CF-LVADs, there was no significant difference in the incidence of major GIB events associated with the use of statin therapy. Further studies are needed to assess whether a true association exists.

Prophylactic Proton Pump Inhibitors in Upper Gastrointestinal Bleeding: Impact and Underprescription in a French Multicentric Cohort.

Appropriate prescription of Proton pump inhibitors (PPIs) remains an important concern amid the rising overuse. A gap exists in the literature regarding the benefit of PPI prophylaxis and the consequences of underprescription in patients at risk for upper gastrointestinal bleeding (UGIB). This study aims to describe the characteristics of hemorrhage in relation to PPI use in patients experiencing UGIB, with a focus on high-risk individuals requiring gastroprotection. Data from a French multicentric cohort of patients experiencing UGIB were analyzed. Patients using PPI were compared to those without PPI considering bleeding etiologies and outcomes of peptic ulcer disease (PUD)-related hemorrhage. The rate of PPI use and its effect on bleeding characteristics in high-risk populations, defined based on international guidelines, were also assessed. Among 2497 included patients, 31.1% were on PPI at bleeding onset. PPI users exhibited a significantly lower rate of PUD-related bleeding in comparison with those without PPI (24.7 vs 40.8%, respectively, p < 0.0001). Similar difference was observed in high-risk populations, of whom, only 40.3% had gastroprotection with PPI before bleeding onset. PPI prophylaxis, however, did not influence the severity of bleeding in the general study population or in high-risk groups. Multivariate analysis identified age, comorbidities, and having more than two anti-thrombotic agents as predictors of severe bleeding. PPI users appear to have a lower rate of bleeding ulcers compared to non-users. However, underprescription in high-risk groups raises the need for standardized care to ensure appropriate PPI use.

Comparative Analysis of Anticoagulation Versus Combination Anticoagulation and Antiplatelet Therapy in Atrial Fibrillation Patients Presenting With Gastrointestinal Bleeding.

Patients with atrial fibrillation (AF) taking antithrombotic (AT) therapy are at increased risk of gastrointestinal bleeding (GIB). The comparative effect of a combination of anticoagulant (AC) and antiplatelet (AP) versus AC monotherapy on clinical outcomes in patients with AF presenting with GIB is not well characterized. This study compares outcomes in AF patients with GIB on AC alone to those on combination AP and AC therapy, as part of a larger prospective study from 2013 to 2023. 137 patients diagnosed with AF who presented with overt GIB were evaluated during their hospitalization, at one month and one year post-discharge, and then annually. The median follow-up of patients was 57 months. Patients in the combination AP +AC therapy group had a higher prevalence of CAD, myocardial infarction, and coronary/vascular stent placement compared to the AC monotherapy group. No statistically significant differences were noted between the two groups in terms of end-of-follow-up mortality, in-hospital mortality, major bleeding, rebleeding, and length of hospital stay. Cox regression analysis revealed chronic kidney disease (CKD) (hazard ratio (HR) 2.05, 95% confidence interval (CI) [1.04,4.05] (p= 0.038)] and warfarin use [(HR 4.94, 95% CI [1.11,22.09] (p= 0.037)] to be independent predictors of mortality at 12 months. Anti-thrombotic therapy in patients with AF who experience GIB should be mainly directed by their cardiovascular needs. Healthcare providers may explore non-vitamin K antagonist oral anticoagulants as alternatives to warfarin for AF patients at risk of GIB, and efforts must be maximized to prevent bleeding in patients with CKD.

Nonvitamin K Anticoagulants: Risk of Bleeding When Interacting With Other Medications: A Cohort Study From Medicare.

Patients on nonvitamin K antagonist (NVKA) are usually taking other drugs. Potential interaction may increase the gastrointestinal (GI) bleeding risk associated with NVKA. Observational cohort study using Medicare data from 2017 to 2020. Participants receiving a NVKA were included. A concomitant overlapping period while on NVKA was assessed for nonsteroidal anti-inflammatory drugs (NSAIDS), selective serotonin reuptake inhibitors (SSRI), antiplatelets, glucocorticoids, aspirin and proton pump inhibitors (PPI). A logistic regression predicting either any bleeding or GI bleeding was conducted estimating the odds ratio (OR) and 95% confidence interval (CI). A total of 102 531 people on NVKA with mean age 77 years (SD = 9.8) and 55% females (N = 56 671) were included. Previous history of GI bleeding occurred in 2 908 (2.8%) participants, concomitant exposure to PPI occurred in 38 713 (38%), SSRI in 16 487 (16%), clopidogrel in 15 795 (15.4%), NSAIDs in 13 715 (13.4%) and glucocorticoids in 13 715 (13.4%). Risk for any bleeding was shown for clopidogrel (OR: 1.37, 95% CI: 1.30, 1.44), prasugrel/ticagrelor (OR: 1.36, 95% CI: 1.18, 1.58), glucocorticoids (OR: 1.26, 95% CI: 1.19, 1.34), and SSRIs (OR: 1.13, 95% CI: 1.07, 1.19). GI bleeding risk was shown for clopidogrel (OR: 1.44, 95% CI: 1.34, 1.55), prasugrel/ticagrelor (OR: 1.47, 95% CI: 1.20, 1.79), SSRIs (OR: 1.09, 95% CI: 1.01, 1.17) and glucocorticoids (OR: 1.33, 95% CI: 1.23, 1.44). PPI use was correlated with both NSAID (r = 0.07, p ≤ 0.0001) and SSRI use (r = 0.09, p ≤ 0.0001). NVKA concomitantly taken with antiplatelets, glucocorticoids, and SSRIs showed an increased risk for any bleeding and GI bleeding.

The relationship between serum uric acid and gastrointestinal bleeding in peritoneal dialysis patients: a propensity score analysis

Purpose Gastrointestinal bleeding is an important gastrointestinal complication among peritoneal dialysis patients and correlated with a higher risk of mortality. Increased uric acid levels are a significant complication for peritoneal dialysis patients and have been associated with an increased risk of hemorrhagic stroke. The objective of the present study was to investigate the relationship between serum uric acid levels and gastrointestinal bleeding in peritoneal dialysis patients. Methods A total of 2498 peritoneal dialysis patients were recruited. Based on the optimal uric acid cutoff value, two groups of patients were divided. We constructed a propensity-score-matched population of 1762 patients by matching sex, age, and body mass index. Survival outcomes between the two groups were compared using adjusted Kaplan–Meier curves. We constructed the restricted cubic splines regression to assess the correlation between levels of uric acid and gastrointestinal bleeding. A multivariate Cox proportional hazards regression was performed to test whether higher levels of uric acid are an independent risk factor for gastrointestinal bleeding. We performed a forest plot to show interaction effects in different subgroups. Results According to restricted cubic splines regression, uric acid levels were positively correlated with the risk of gastrointestinal bleeding events. After adjusted different confounding factors, patients with high levels of uric acid were prone to experience gastrointestinal bleeding (HR 1.868, 95%CI 1.001–3.486). In subgroups, the interaction between higher levels of uric acid and utilizing proton pump inhibitors was significant (P for interaction = 0.034). Further research found that taking proton pump inhibitors could decrease the risk of gastrointestinal bleeding in peritoneal dialysis patients accompanied high levels of uric acid. Conclusion The baseline high levels of uric acid are an independent risk factor for gastrointestinal bleeding in patients undergoing peritoneal dialysis.

Multicenter retrospective cohort study demonstrates superior safety profile of indobufen over aspirin for Post-CABG antiplatelet therapy.

Coronary artery bypass grafting (CABG) is essential for treating coronary artery disease, with postoperative aspirin crucial to prevent graft restenosis. However, its gastrointestinal side effects may limit tolerability in some patients. Indobufen presents a potential alternative, but its safety and efficacy need further validation. This study aimed to compare the efficacy and safety of indobufen versus aspirin in patients' post-CABG. This retrospective observational study included 39 patients who underwent CABG at two centers from January to December 2023. Patients were retrospectively assigned to two groups based on the antiplatelet therapy they received: the indobufen group (n = 19) and the aspirin group (n = 20). The primary endpoint was a composite of non-fatal myocardial infarction, stroke, and revascularization due to acute coronary syndrome in the intention-to-treat population. Postoperative data on platelet count, hemoglobin, D-dimer, activated partial thromboplastin time (APTT), and hospital stay length were collected. Transfusion rate, bleeding, thrombotic events, and gastrointestinal adverse reactions were compared between the two groups. Over the 8-to-18-month follow-up period, 5 patients (25%) in the aspirin group reached the primary endpoint, while none in the indobufen group did, a difference that was statistically significant (p = 0.02). Although the rates of non-fatal myocardial infarction, revascularization, stroke, and thrombotic events were higher in the aspirin group, these differences did not reach statistical significance. Importantly, the total bleeding events were markedly lower in the indobufen group (15.79% vs. 55%, p = 0.011), with major bleeding events also significantly reduced in the indobufen group (0% vs. 20%, p = 0.04). Both groups showed no significant differences were observed in postoperative hospital stay, hemoglobin, and D-dimer levels between the groups. However, the indobufen group demonstrated significantly lower platelet count and APTT. The average daily cost of indobufen was 27.8 times higher than that of aspirin. Indobufen demonstrates a comparable antiplatelet effect to aspirin and offers significant advantages in reducing gastrointestinal adverse reactions and bleeding risk. It can be considered a preferable alternative for patients who cannot tolerate or have contraindications to aspirin. Further large-scale clinical trials are needed to confirm its potential as the first-choice antiplatelet therapy post-CABG.

Is dabigatran a good alternative to warfarin in patients with atrial fibrillation accompanied by valvular and nonvalvular heart diseases? A systematic review and meta-analysis

Abstract Background There is ongoing discussion regarding the terminology used when atrial fibrillation (AF) is present alongside either valvular heart disease (VHD) or non-valvular heart disease (NVHD). Warfarin has been used for decades for stroke (S) and systemic embolism (SE) prophylaxis in atrial fibrillation (AF) patients. However, due to its drug and food interactions, pharmacogenetic approach via VKORC1, narrow therapeutic window, frequent monitoring, and high risk of intracranial hemorrhage (ICH), it is not preferred as a first-line anticoagulant for AF patients. Is it time to retire warfarin and replace it with dabigatran? Aim and objectives We conducted this meta-analysis to assess the effectiveness and safety of dabigatran compared to warfarin and find out how likely it could be used instead of warfarin in AF patients with VHD and NVHD. Methods PubMed, SCOPUS, Web of Science, and Cochrane CENTRAL were searched online from inception till June 2023, and eligible randomized controlled trials (RCTs) were selected. The outcomes were analyzed and calculated using the risk ratio (RR), and its confidence interval (CI) using STATA software. The Cochrane Risk of Bias 2.0 tool (ROB2) was used to assess the included studies. Results In the NVHD subgroup, dabigatran 150 mg showed a significantly low risk of S and SE (RR 0.74, 95% CI: [0.62,0.88]), ICH (RR 0.38, 95% CI: [0.26,0.56]), death (RR 0.85, 95% CI: [0.74,0.99]), and high risk of gastrointestinal bleeding (GIB) (RR 1.47, 95% CI: [1.17,1.85]) compared to Warfarin. Dabigatran 110 mg showed a low risk of ICH (RR 0.31, 95% CI: [0.21,0.47]), and no significant differences in S/SE (RR 1.02, 95% CI: [0.87,1.19]) and death (RR 0.94, 95% CI: [0.82,1.09]) compared to warfarin. In the VHD subgroup, dabigatran showed no significant differences in S/SE (RR 2.57, 95% CI: [0.57,11.56]), major bleeding (RR 1.14, 95% CI: [0.35,3.68]), and death (RR 0.35, 95% CI: [0.07,1.81]) compared to warfarin. In the catheter ablation subgroup, dabigatran showed a significant reduction only in groin hematoma (RR 0.19, 95% CI: [0.05,0.73]), compared to warfarin. Conclusion Dabigatran 150 mg was superior to warfarin in AF patients with NVHD; except with GIB; otherwise, Dabigatran 110 mg was superior only to warfarin in reducing ICH. In catheter ablation, dabigatran only reduced the groin hematoma. In AF patients with VHD, dabigatran did not show either superiority or inferiority to warfarin, further studies are needed. “Non-valvular AF” term is outdated and should be replaced with “type II VHD” to differentiate it from other valvular heart diseases that are accompanied by AF.

Comparison of Oral Anticoagulants vs. Warfarin for Stroke Prevention in Atrial Fibrillation: A Meta-Analysis

Background: Atrial fibrillation (AF) significantly increases the risk of ischemic stroke, necessitating effective anticoagulation therapy. Warfarin has been the standard treatment, but direct oral anticoagulants (DOACs) have emerged as a safer and more effective alternative.Objective: To compare the efficacy and safety of DOACs versus warfarin in stroke prevention among AF patients.Methods: A comprehensive literature search was conducted in PubMed, EMBASE, Cochrane Library, Web of Science, and Scopus following PRISMA guidelines. Randomized controlled trials and observational studies comparing DOACs (dabigatran, rivaroxaban, apixaban, edoxaban) with warfarin in AF patients were included. Primary outcomes were ischemic stroke or systemic embolism, and secondary outcomes included all-cause mortality, major bleeding, intracranial hemorrhage (ICH), and gastrointestinal bleeding. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using a random-effects model.Results: A total of 35 studies involving 172,350 patients were analyzed. DOACs significantly reduced ischemic stroke or systemic embolism (HR: 0.78, 95% CI: 0.72–0.84, p &lt; 0.001) and all-cause mortality (HR: 0.85, 95% CI: 0.79–0.92, p = 0.002). Major bleeding risk was lower (HR: 0.88, 95% CI: 0.80–0.96, p = 0.005), but gastrointestinal bleeding was higher (HR: 1.20, 95% CI: 1.10–1.30, p &lt; 0.001).Conclusion: DOACs provide superior efficacy and safety in stroke prevention compared to warfarin, despite a higher risk of gastrointestinal bleeding.

Cardiac thrombus in acute ischemic stroke: impact on endovascular thrombectomy utilization

Cardiac embolism plays a very significant role in acute ischemic strokes (AIS), constituting approximately one-third of cases. The origin of these emboli often stems from intracardiac thrombi in the left atrium or left ventricle. Utilizing the National Readmission Database from 2016 to 2019, we investigate the prevalence of cardiac thrombi in AIS patients and explore their potential correlation with endovascular thrombectomy (EVT) utilization, and mortality rates. Among 1,272,456 AIS patients, 0.6% had concurrent cardiac thrombus, with an increasing trend observed over the study period (P value < 0.001). The cardiac thrombus cohort showed a higher prevalence of comorbidities such as congestive heart failure and atrial fibrillation. After propensity-score matching, groups were well-balanced in terms of baseline characteristics. Patients within the cardiac thrombus cohort experienced a longer hospital stay (median 5 days vs. 3 days), but no significant difference in mortality was noted. Importantly, the cardiac thrombus cohort demonstrated a higher frequency of EVT utilization, suggesting a link to larger vessel occlusions. Despite matching based on atrial fibrillation, the EVT utilization in the cardiac thrombus cohort remained high, highlighting a significant association. While 30-day readmission rates were comparable, cardiac thrombus patients faced a higher risk of gastrointestinal bleeding and hemorrhagic stroke, likely attributed to anticoagulation use. Limitations include potential miscoding in the administrative database and a lack of detailed imaging findings. In conclusion, this study highlights the increased likelihood of EVT in AIS patients with cardiac thrombus, possibly indicative of larger vessel occlusion associated with cardiac thrombus.

Type 2 Diabetes Mellitus and Helicobacter pylori Gastritis in Patients Referred for Endoscopy-A Single-Center Romanian Study.

Type 2 diabetes mellitus (T2DM) affects up to 10% of adults globally, and its complications can mask the risk of gastrointestinal bleeding or malignancy. Our study enrolled 633 endoscopic patients stratified according to T2DM presence (4:1 ratio in favor of the control group). T2DM patients referred for endoscopy experienced lower prevalence of epigastric pain and heartburn (OR = 0.637/OR = 0.346, p < 0.05). Often being anemic (OR = 2.23, p < 0.001), they had significantly lower hemoglobin (p = 0.001) and serum iron (p = 0.02), but serum cholesterol was higher in non-diabetics. Ulcers, erosions and mucosal hemorrhages were comparable between groups (p < 0.05), although low-dose aspirin use was more prevalent in diabetics (p = 0.000, OR = 2.34). T2DM was associated with the increased frequency of antro-corporal active gastritis (OR = 1.451/OR 1.501), with smokers presenting a higher frequency of active H. pylori infection (OR = 3.37). T2DM predicted anemia (adjusted OR = 1.70) and the absence of gastroesophageal reflux symptoms (adjusted OR = 0.37), but not active H. pylori gastritis or premalignant lesions. In an endoscopic population, patients with T2DM had lower hemoglobin and serum iron levels. There was an inverse correlation between T2DM and heartburn. H. pylori gastritis and premalignant lesions occurred more frequently in diabetic patients (predominantly pangastritis) before adjusting for age or associated comorbidities, with smoking increasing the risk for active infection.

Comparative incidence and risk factors for gastrointestinal bleeding following percutaneous coronary intervention for coronary artery disease: Insights from the Keio Cardiovascular Registry in Japan

BackgroundIn patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI), antiplatelet medication usage is crucial for preventing thrombotic events. However, it requires careful monitoring, especially because of the risk of life-threatening bleeding complications. In hemorrhagic complications, assessment of patient background and risk of gastrointestinal bleeding (GIB) remain limited for GIB that develops during long-term observation after hospital discharge. This study aimed to examine the incidence of GIB and patient characteristics in CAD post-PCI. MethodsAll CAD patients undergoing PCI for urgent, emergent, or elective indications were enrolled in the Keio Interhospital Cardiovascular Studies (JCD-KiCS)-PCI registry (January 2009 and December 2017) and followed up to 2 years after PCI discharge. From the JCD-KiCS PCI registry, 8864 patients (median [interquartile range [IQR]] age: non-GIB: 69.0 y [16 y], upper GIB (UGI): 72.0 y [15.5 y], lower GIB (LGI): 73.0 y [IQR: 13 y]) were categorized based on the occurrence of hospitalization-requiring GIB. Patient characteristics and detailed information regarding these GIB events, including the location (upper vs lower GI) and bleeding severity, were analyzed. ResultsOverall, 36 patients experienced UGI, while 85 patients experienced LGI. The rates of dual antiplatelet therapy (DAPT) and triple therapy were significantly different among the non-GIB (n = 8734), UGI (n = 36) and LGI (n = 85) groups (DAPT [aspirin + P2Y12 (clopidogrel/prasugrel/ticlopidine)]: 64 [76.2 %] in the LGI group vs 24 [68.6 %] in the UGI group vs 7330 [84.6 %] in the non-GIB group; triple therapy [aspirin + P2Y12 (clopidogrel/prasugrel/ticlopidine)] + oral anticoagulant (OAC) (warfarin/direct oral anticoagulant [DOAC]): 17 [20.2 %] in the LGI group vs 8 [22.9 %] in the UGI group vs 836 [9.6 %] in the non-GIB group; p < 0.001). In the LGI and UGI groups, aspirin and warfarin were used in 2 (2.4 %) and 2 (5.7 %) patients, respectively, but not in combination with DOAC. The 2-year post-PCI hospitalization incidence for GIB was 1.4 % (LGI, 1.0 %; UGI, 0.4 %). The most common causes were colonic diverticular hemorrhage (43.5 %) for LGI and duodenal ulcer (21.9 %) for UGI. No significant differences were found in the cumulative 2-year post-PCI risks between the LGI and UGI groups (log-rank p = 0.97). Most GIB events were Bleeding Academic Research Consortium 2-equivalent (hemoglobin decrease <3 g/dL). Notably, the use of OACs at PCI discharge, bleeding complications within 72 h, and preprocedural anemia were significantly correlated with an increased GIB risk. ConclusionsThe real-world incidence of LGI is two times higher than that of UGI in CAD patients undergoing PCI, and most events are mild. OAC use at PCI discharge is the strongest potential risk factor for GIB development.

Gastrointestinal Bleeding After Percutaneous Coronary Intervention: Incidence, Risk Factors, and Outcomes.

Percutaneous coronary intervention (PCI) is a well-established method for treating coronary artery disease. However, stent implantation necessitates the use of antiplatelet agents, which increases the risk of gastrointestinal bleeding (GIB). This study aims to assess the incidence, etiology, and outcomes of GIB within one year post-PCI at Sultan Qaboos University Hospital (SQUH), Muscat, Oman. This retrospective analysis included 435 patients who underwent PCI at SQUH between January and December 2017, excluding those with multiple PCI procedures and incomplete data. GIB was defined using the thrombolysis in myocardial infarction (timi) bleeding score. Statistical analysis was performed using IBM SPSS Statistics for Windows, version 23 (IBM Corp., Armonk, NY) with binary logistic regression employed to identify significant risk factors for GIB. A p-value < 0.05 was considered statistically significant. GIB was identified in 15 patients (age 67.8 ± 8.8 years; 60% male), resulting in an incidence within one year post-PCI of 3.4%. Melena (53.3%) and hematemesis (20.0%) were the most frequent clinical presentations, with peptic ulcer disease being the predominant underlying etiology (40%). Significant risk factors included advanced age, chronic kidney disease, pre-existing peptic ulcer disease, and the use of non-steroidal anti-inflammatory drugs. The incidence of GIB observed in this study aligns with previously reported rates. These findings highlight the importance of pre-PCI risk stratification for bleeding, especially in high-risk patients. Prophylactic measures, such as the use of gastric protective agents, should be considered to mitigate the risk of GIB in patients undergoing PCI.

Comparative Effectiveness and Safety of Off-Label Underdosed Direct Oral Anticoagulants in Asian Patients with Atrial Fibrillation: A Systematic Review and Meta-analysis.

Off-label underdosed direct oral anticoagulants (DOACs) are commonly utilised in Asian patients with atrial fibrillation (AF) since they are prone to bleeding with OACs. However, the efficacy and safety of off-label underdosing DOACs are controversial. This study aimed to compare the effectiveness and safety of off-label underdosed DOACs in Asian patients with AF. PubMed, Embase, Cochrane library, and ClinicalTrials.gov were searched from 2010 to July 5, 2024, for randomised controlled trials or observational studies that compared off-label DOACs and on-label/warfarin in Asian patients with AF. The primary outcomes included ischaemic stroke or systemic embolism (ISSE) and major bleeding (MB), while secondary outcomes included all-cause death, gastrointestinal bleeding (GIB), intracranial haemorrhage (ICH), and myocardial infarction (MI). Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled using random-effects models. Twenty observational studies were included. Seventeen studies compared off-label underdosed DOACs versus on-label DOACs, whereas five studies compared off-label underdosed DOACs versus warfarin. Off-label underdosed DOACs were associated with higher risk of ISSE (pooled HR [pHR] = 1.17; 95% CI: 1.00-1.38, p = 0.048) and ICH (pHR = 1.27; 95% CI: 1.06-1.52, p = 0.010) versus on-label. Subgroup analysis demonstrated increased ISSE risk with off-label underdosed rivaroxaban compared to on-label (pHR = 1.49; 95% CI: 1.07-2.08). Compared to warfarin, off-label underdosed DOACs were associated with decreased risk of MB (pHR = 0.46; 95% CI: 0.32-0.65, p < 0.001), GIB (pHR = 0.52; 95% CI: 0.29-0.93, p = 0.028), ICH (pHR = 0.60; 95% CI: 0.42-0.86, p = 0.005), and all-cause death (pHR = 0.70; 95% CI: 0.56-0.87, p = 0.001), while illustrating similar ISSE risk. Off-label underdosed DOACs, particularly rivaroxaban, was associated with increased ISSE risk but did not decrease bleeding compared to on-label. Adherence to appropriate DOAC doses should be emphasised to achieve the best clinical outcomes for Asian patients with AF.

Nonsteroidal anti-inflammatory drug use by patients: Impact of modular educational training on pharmacists' questioning, counselling and risk assessments

BackgroundNonsteroidal anti-inflammatory drugs (NSAIDs)-related morbidity and mortality can be reduced through medication counselling and risk reduction. ObjectivesThis study evaluated the impact of short online modular NSAID training on the type and quality of questions asked, risk factors assessed, and counselling offered by community pharmacists to NSAID users. MethodsA cross-sectional questionnaire-guided survey conducted in Ibadan, Nigeria, among 87 pharmacists evaluated the frequency of counselling, NSAID risk factor assessment and barriers to risk assessment. Additionally, a before-and-after RCT was used to evaluate the impact of short online modular NSAID training for the intervention group (IG) on the type and quality of the questions asked, counselling provided, and risk assessed by the pharmacists. Eight standardised patients, aged 25–43 years, four at pre- and postintervention, presented four standardised scenarios at community pharmacies [IG, n = 22, control group (CG, n = 30)] to assess these outcomes. The quality of each outcome (questions asked, counselling offered and risk assessed) was classified as poor (0–≤20%), fair (>20–≤40%), moderate (>40 – ≤60%), or optimal (>60–100%). The data are presented with descriptive statistics. ResultsThe community pharmacists reported counselling patients on NSAID precautions (80–86%) and dosages (51–69%). Gastrointestinal bleeding risk was assessed by 61–89% of the pharmacists, and time constraints (39–42%) and patient impatience (47–75%) were some barriers to risk assessment. Online modular educational intervention significantly improved the types and quality of questions asked by pharmacists (CG: poor to fair, 16%–21%; IG: poor to moderate, 14%–45%), NSAID risk factors assessed (CG: poor to poor, 10%–9%; IG: poor to fair, 11%–27%) and counselling offered (CG: poor to poor, 6%–7%; IG: poor to fair, 6%–22%). ConclusionsShort online modular educational training on NSAIDs improved the types and quality of the questions asked, NSAID risk factors assessed, and counselling provided by community pharmacists to patients during consultations.

Risk of gastrointestinal bleeding in Asian patients receiving oral anticoagulants for stroke prevention in atrial fibrillation.

Non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly used for stroke prevention in atrial fibrillation. At the Asia Pacific Advancing Patient care with EdoXaban 2023 meeting, experts shared insights on gastrointestinal bleeding with NOACs for stroke prevention in atrial fibrillation in Asian clinical practice, where NOACs have gained widespread acceptance due to their favourable profiles. Gastrointestinal bleeding risk varies amongst NOACs, emphasizing the importance of diligent patient assessment, dosage selection and vigilant monitoring. Edoxaban emerged as a viable option with a low gastrointestinal bleeding risk profile in Asian compared with non-Asian patients, supporting its continued clinical utilization for appropriate patients.