Higher Risk Of Gastrointestinal Bleeding Research Articles

Comparative effectiveness of rivaroxaban versus warfarin or dabigatran for the treatment of patients with non-valvular atrial fibrillation

BackgroundRivaroxaban is an oral anticoagulant approved in the US for prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF). We determined the effectiveness and associated risks of rivaroxaban versus other oral anticoagulants in a large real-world population.MethodsWe selected NVAF patients initiating oral anticoagulant use in 2010–2014 enrolled in MarketScan databases. Rivaroxaban users were matched with warfarin and dabigatran users by age, sex, enrolment date, anticoagulant initiation date, and high-dimensional propensity score. Study endpoints, including ischemic stroke, intracranial bleeding (ICB), myocardial infarction (MI), and gastrointestinal (GI) bleeding, were identified from inpatient diagnostic codes. Multivariable Cox models were used to assess associations between type of anticoagulant and outcomes.ResultsThe analysis included 44,340 rivaroxaban users matched to 89,400 warfarin and 16,957 dabigatran users (38% female, mean age 70) with 12 months of mean follow-up. Anticoagulant-naïve rivaroxaban initiators, but not those switching from warfarin, had lower risk of ischemic stroke [hazard ratio (HR) (95% confidence interval (CI)): 0.75 (0.62, 0.91)] and ICB [HR (95%CI): 0.55, (0.39, 0.78)] than warfarin users. In contrast, anticoagulant-experienced rivaroxaban initiators had higher risk of GI bleeding than warfarin users [HR (95%CI): 1.55 (1.32, 1.83)]. Endpoint rates were similar when comparing anticoagulant-naïve rivaroxaban and dabigatran initiators, with the exception of higher GI bleeding risk in rivaroxaban users [HR (95%CI) 1.28 (1.06, 1.54)]. There were no significant differences in the risk of MI among the comparison groups.ConclusionIn this large real-world sample of NVAF patients, effectiveness and risks of rivaroxaban versus warfarin differed by prior anticoagulant status, while effectiveness of rivaroxaban versus dabigatran differed in GI bleeding risk.

Efficacy and safety of non-vitamin K antagonist oral anticoagulants compared with warfarin in patients with atrial fibrillation

AimsNon-vitamin K antagonist oral anticoagulants (NOACs) were in pivotal randomised controlled trials at least non-inferior to warfarin for stroke prevention in atrial fibrillation, but time in therapeutic range (TTR) for...

45 Rivaroxaban vs. dabigatran or warfarin in real-world observational studies of stroke prevention in atrial fibrillation: systematic review and meta-analysis

ObjectiveTo evaluate the effectiveness and safety of rivaroxaban in real-world practice compared with dabigatran (R vs. D) or with warfarin (R vs. W) for stroke prevention in atrial fibrillation (AF)....

Application of degree of portal systemic shunting in assessing upper gastrointestinal bleeding in patients with schistosomiasis cirrhosis

To discuss the application of the degree of portal systemic shunting in assessing the upper gastrointestinal bleeding in patients with hepatic schistosomiasis. Thirty-three patients with upper gastrointestinal bleeding caused by hepatic schistosomiasis (a bleeding group) and 29 schistosomiasis cirrhosis patients without bleeding (a non-bleeding group) were enrolled as investigation subjects in Jinshan Hospital. The subjects were scanned by the 128 abdominal slice spiral CT. The portal systemic shunting vessels were reconstructed by using thin slab maximum intensity projection (TSMIP) and multiplanar reconstruction (MPR). The degrees of the shunting vessels of the subjects were evaluated and compared, and the relationship between upper gastrointestinal bleeding and the degree of the shunting was analyzed. In the bleeding group, the occurrence rates of the shunting vessels were found as follows: 86.4% in left gastric varices, 68.2% in short gastric varices, 50.0% in esophageal varices, 50.0% in para-esophageal varices, 37.9% in gastric varices, 69.7% in gastric-renal varices, 51.5% in spleen-renal varices, 25.8% in abdominal wall varices, 15.2% in omentum varices, 63.6% in para-splenic varices, 34.8% in umbilical varices, 40.9% in retroperitoneal-paravertebral varices, and 36.4% in mesenteric varices. In the bleeding group, the occurrence rates and the degree of shunt were significantly higher than those in the non-bleeding group in esophageal varices, esophageal vein, left gastric vein and gastric varices (all P < 0.05). CT portal vein reconstruction can accurately display the location, degree and walking of all kinds of shunting vessels. Esophageal varices, esophageal vein, left gastric vein and gastric varices can accurately predict the risk of upper gastrointestinal bleeding in patients with hepatic schistosomiasis. The patents with higher degree of the shunting vessels have a higher risk of gastrointestinal bleeding.

Shear stress alterations in the celiac trunk of patients with a continuous-flow left ventricular assist device as shown by in-silico and in-vitro flow analyses

The use of left ventricular assist devices (LVADs) to treat advanced cardiac heart failure is constantly increasing, although this device leads to high risk for gastrointestinal bleeding. Using in-silico flow analysis, we quantified hemodynamic alterations due to continuous-flow LVAD (HeartWare, Inc., Framingham, MA) in the celiac trunk and major branches of the abdominal aorta, and then explored the relationship between wall shear stress (WSS) and celiac trunk orientation. To assess outflow from the aortic branch, a 3-dimensional-printed patient-specific model of the celiac trunk reconstructed from an LVAD-supported patient was used to estimate echocardiographic outflow velocities under continuous-flow conditions, and then to calibrate computational simulations. Moreover, flow pattern and resulting WSS values were computed for 5 patients with LVAD implantation. Peak WSS values were estimated on the 3 branches of the celiac trunk and the LVAD cannula. The mean WSSs demonstrated that the left gastric artery underwent the highest WSS of 9.08 ± 5.45 Pa, with an average flow velocity of 0.57 ± 0.25 m/s compared with that of other vessel districts. The common hepatic artery had a less critical WSS of 4.58 ± 1.77 Pa. A positive correlation was found between the celiac trunk angulation and the WSS stress just distal to the ostium of the celiac trunk (R = 0.9), which may increase vulnerability of this vessel to bleeding. Although further studies are needed to confirm these findings in a larger patient cohort, computational flow simulations may enhance the information of clinical image data and may have an application in clinical investigations of hemodynamic changes in LVAD-supported patients.

Duodenal ulcers are a major cause of gastrointestinal bleeding after cardiac surgery

ObjectiveTo determine the incidence of gastrointestinal (GI) bleeding in patients after cardiac surgery, assess the perioperative risk factors, and determine the type of GI tract pathology associated with bleeding events. MethodsAt a tertiary referral hospital, all cardiac surgery patients having a postoperative GI bleed from April 2002 to March 2012 were identified. To determine bleeding etiology, only patients requiring endoscopy were included in the analysis. By retrospective review of 3 prospectively maintained databases, the incidence and independent predictors of GI bleeding, as well as endoscopic findings, were determined. ResultsNinety-one GI bleeding events that required endoscopy were identified in 9017 patients. Those that bled were aged 71 ± 12 years, and 76% were men. Sixty-three percent of these patients had valve surgery and 37% had an isolated coronary artery bypass grafting. The overall incidence of GI bleeding was 1.01%, with an upper GI source accounting for 78%. Endoscopy data found a duodenal ulcer as the bleeding source in 71%, whereas stress gastritis accounted for 8%. Preoperative risk factors for bleeding included age ≥70 years, ejection fraction <35%, congestive heart failure, cerebrovascular disease, chronic kidney disease, and gastrointestinal disease. A preoperative history of atrial fibrillation and anticoagulation with Coumadin also was associated with bleeding. Patients that bled had a 30-day mortality rate of 8.8%, which was significantly greater than patients who did not bleed (4.3%; P = .03). ConclusionsClinical variables can be used to identify patients at high risk for GI bleeding after cardiac surgery. When GI bleeding occurs, the most common cause is duodenal ulceration, which has an association with Helicobacter pylori infection. These findings may provide an opportunity to initiate preoperative preventative strategies.

The Morbidity and Mortality Risks following Percutaneous Coronary Interventions in Cirrhosis

Background: The prevalence of coronary artery disease in cirrhotic population is estimated to be low and the risk of bleeding in those who had percutaneous catheterization interventions (PCI) is not well studied yet. Our aim in this study is to determine the morbidity and mortality risks in cirrhotic patient undergoing PCI. Methods: We performed a retrospective analysis using the National Inpatient Sample (NIS) database for 2010. The NIS is the largest publicly available inpatient health care database in the United States. It contains data from more than 7 million hospital stays each year. People with Percutaneous coronary intervention (PCI) related admissions and a history of cirrhosis diagnosis were placed in the case group. Equivalent number of people with PCI related admissions and no history of cirrhosis were identified randomly and Case-Control (PCI with cirrhosis vs. PCI without cirrhosis) design is used. All genders, race was with age of 18-year-old and above was included. A binary multivariate Logistic regression statistical test was used to examine the probability difference adjusted odd ratio. IBM SPSS Statistics for Windows was used to execute the analysis. A confidence interval (CI) of 95% and P value less than 0.05 were determined to define significance. Results: A total of 1218 of PCI related admissions were identified. 609 PCI related admissions with cirrhosis (Cases group) and equivalent number of 609 admissions with PCI and no cirrhosis (Control group) were randomly selected. 83.5% of the cohort represented by white race followed by Hispanic and African-American percentages of 10% and 6.5% respectively. The mean age of the cohort was 60 years, 54% represented by male race. The mean length of stay was 1.06 in the non-cirrhosis group compared to the 1.65 days in the cirrhosis group. Tables 1 and 2 (0.3%) out of 609 PCI related admission and no history of cirrhosis group had an Upper Gastrointestinal bleeding (UGIB) Vs. 11 (1.8%) in the PCI related admission with history of cirrhosis group. Inpatient mortality in the PCI+ non Cirrhosis group was 0.3% vs. 1.8% in the PCI and Cirrhosis group. The probability of dying during hospitalization for PCI related admission and have history of cirrhosis is 5 times higher than having a PCI without history of Cirrhosis with an adjusted odd ratio of 5.5(P-Value 0.026). Conclusion: There is a significantly higher risk of gastrointestinal bleeding and mortality in cirrhotic patients compared to the non-cirrhotic patients who underwent PCI.

Thrombosis in the setting of obesity or inflammatory bowel disease.

Obesity and inflammatory bowel disease (IBD) are systemic inflammatory disorders that predispose to arterial and venous thrombosis through similar prothrombotic mechanisms. Obesity and IBD are chronic risk factors that lead to a persistently elevated risk of thrombosis, although the thrombotic risk with IBD appears to wax and wane with disease severity. Because of the lack of high-quality evidence to guide management decisions, approaches to the prevention and treatment of thrombosis in patients with obesity or IBD are based on extrapolation from general guidelines for antithrombotic therapy. Obesity alters the pharmacokinetics of some anticoagulant drugs, and IBD patients present the added management challenge of having a high risk of gastrointestinal bleeding while taking anticoagulants. An extended duration of anticoagulant therapy is often recommended for obese or IBD patients with unprovoked venous thromboembolism unless there is a high risk of bleeding, although more data and better biomarkers are needed to determine whether anticoagulation can be safely stopped in a subset of IBD patients during remission of active disease. Most patients with obesity or IBD require thromboprophylaxis in conjunction with hospitalization or surgery, with adjustment of anticoagulant dosing in patients with severe obesity.

Temporal Trends, Predictors, and Outcomes of In-Hospital Gastrointestinal Bleeding Associated With Percutaneous Coronary Intervention

Since the introduction of new antiplatelet and anticoagulant agents in the last decade, large-scale data studying gastrointestinal bleeding (GIB) in patients undergoing percutaneous coronary intervention (PCI) are lacking. Using the Nationwide Inpatient Sample, we identified all hospitalizations from 2006 to 2012 that required PCI. Temporal trends in the incidence and multivariate predictors of GIB associated with PCI were analyzed. A total of 4,376,950 patients underwent PCI in the United States during the study period. The incidence of GIB was 1.1%. Mortality rate in the GIB group was significantly higher (9.71% vs 1.1%, p <0.0001). Although the incidence of GIB remained stable during the study period (0.97% in 2006 to 1.19% in 2012), in-hospital mortality rate increased significantly from 7.9% in 2006 to 10.78% in 2012, with a peak of 12% in 2010. The GIB group had a longer median length of stay (5.80 vs 1.57days) and an increased median cost of hospitalization ($26,564 vs $16,879). The predictors of GIB included cardiovascular co-morbidities such as acute myocardial infarction, cardiogenic shock, atrial fibrillation, congestive heart failure, valvular heart diseases, and a history of transient ischemic attack/stroke. Gastrointestinal co-morbidities including diverticulosis, esophageal cancer, stomach cancer, small intestine cancer, large intestine cancer, rectosigmoid cancer, gastrointestinal ulcer, and liver disease were predictors of GIB. Interestingly, a lower risk of GIB was associated with obese patients and patients with private insurance. A higher risk of GIB was noted in urgent versus elective admissions and weekend versus weekday admissions. In conclusion, the incidence of GIB in patients who underwent PCI remained stable from 2006 to 2012; however, thein-hospital mortality increased significantly. Identifying patients at higher risk for GIBis critically important to develop preventive strategies to reduce morbidity and mortality.

Minimizing the Risk of Bleeding with NOACs in the Elderly.

Novel oral anticoagulants (NOACs) such as dabigatran, rivaroxaban, apixaban and edoxaban have gained a lot of popularity as alternatives to warfarin for anticoagulation in various clinical settings. However, there is conflicting opinion regarding the absolute benefit of NOAC use in elderly patients. Low body mass, altered body composition of fat and muscle, renal impairment and concurrent presence of multiple comorbidities predispose elderly patients to many adverse effects with NOACs that are typically not seen in younger patients. There have been reports that NOAC use, in particular dabigatran, is associated with a higher risk of gastrointestinal bleeding in the elderly. Diagnosis and management of NOAC-associated bleeding in the elderly is difficult due to the absence of commonly available drug-specific antidotes that can rapidly reverse the anticoagulant effects. Moreover, in elderly patients, a number of factors such as the presence of other comorbid medical conditions, renal insufficiency, drug interactions from polypharmacy, risk of falls and dementia need to be considered before prescribing anticoagulation therapy. Elderly patients frequently have compromised renal function, and therefore dose adjustments according to creatinine clearance for NOACs need to be made. As each NOAC comes with its own unique advantages and safety profile, an individualized case by case approach should be adopted to decide on the appropriate anticoagulation regimen for elderly patients after weighing the overall risks and benefits of therapy.

Impact of concomitant use of proton pump inhibitors and clopidogrel or ticagrelor on clinical outcomes in patients with acute coronary syndrome.

BackgroundThere is great debate on the possible adverse interaction between proton pump inhibitors (PPIs) and clopidogrel. In addition, whether the use of PPIs affects the clinical efficacy of ticagrelor remains less known. We aimed to determine the impact of concomitant administration of PPIs and clopidogrel or ticagrelor on clinical outcomes in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI).MethodsWe retrospectively analyzed data from a “real world”, international, multi-center registry between 2003 and 2014 (n = 15,401) and assessed the impact of concomitant administration of PPIs and clopidogrel or ticagrelor on 1-year composite primary endpoint (all-cause death, re-infarction, or severe bleeding) in patients with ACS after PCI.ResultsOf 9429 patients in the final cohort, 54.8% (n = 5165) was prescribed a PPI at discharge. Patients receiving a PPI were older, more often female, and were more likely to have comorbidities. No association was observed between PPI use and the primary endpoint for patients receiving clopidogrel (adjusted HR: 1.036; 95% CI: 0.903–1.189) or ticagrelor (adjusted HR: 2.320; 95% CI: 0.875–6.151) (Pinteraction = 0.2004). Similarly, use of a PPI was not associated with increased risk of all-cause death, re-infarction, or a decreased risk of severe bleeding for patients treated with either clopidogrel or ticagrelor.ConclusionsIn patients with ACS following PCI, concomitant use of PPIs was not associated with increased risk of adverse outcomes in patients receiving either clopidogrel or ticagrelor. Our findings indicate it is reasonable to use a PPI in combination with clopidogrel or ticagrelor, especially in patients with a higher risk of gastrointestinal bleeding.

Abstract P005: Comparative Effectiveness of Rivaroxaban versus Warfarin for the Treatment of Patients with Non-valvular Atrial Fibrillation

Background: Rivaroxaban is a novel oral anticoagulant approved in the US in 2011 for prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF). Information on risks and benefits among rivaroxaban users in real-world populations is limited. Methods: We used data from the US MarketScan Commercial and Medicare Supplemental databases between 2010 and 2013. We selected patients with a history of NVAF and initiating rivaroxaban or warfarin. Rivaroxaban users were matched with up to 5 warfarin users by age, sex, database enrollment date and drug initiation date. Ischemic stroke, intracranial bleeding (ICB), myocardial infarction (MI), and gastrointestinal (GI) bleeding outcomes were defined by ICD-9-CM codes in an inpatient claim after drug initiation date. Cox proportional hazards models were used to assess the association between rivaroxaban vs. warfarin use and outcomes adjusting for age, sex, and CHA2DS2-VASc score. Separate models were used to compare a) new rivaroxaban users with new warfarin users, and b) switchers from warfarin to rivaroxaban to continuous warfarin users. Results: Our analysis included 34,998 rivaroxaban users matched to 102,480 warfarin users with NVAF (39% female, mean age 71), in which 487 ischemic strokes, 179 ICB, 647 MI, and 1353 GI bleeds were identified during a mean follow-up of 9 months. Associations of rivaroxaban vs warfarin were similar in new users and switchers; therefore we pooled both analyses. Rivaroxaban users had lower rates of ICB (hazard ratio (HR) (95% confidence interval (CI)) = 0.72 (0.46, 1.12))) and ischemic stroke (HR (95% CI) = 0.88 (0.68, 1.13)), but higher rates of GI bleeding (HR (95% CI) = 1.15 (1.01, 1.33)) when compared to warfarin users (table). Conclusion: In this large population-based study of NVAF patients, rivaroxaban users had a non-significant lower risk of ICB and ischemic stroke than warfarin users, but a higher risk of GI bleeding. These real-world findings are comparable to results reported in published clinical trials.

40-Year-Old Woman With Breathlessness and Fatigue

40-Year-Old Woman With Breathlessness and Fatigue

Choosing a particular oral anticoagulant and dose for stroke prevention in individual patients with non-valvular atrial fibrillation: part 2.

The choice of oral anticoagulant (OAC) for patients with atrial fibrillation (AF) may be influenced by individual clinical features or by patterns of risk factors and comorbidities. We reviewed analyses of subgroups of patients from trials of vitamin K antagonists vs. non-vitamin K oral anticoagulants (NOACs) for stroke prevention in AF with the aim to identify patient groups who might benefit from a particular OAC more than from another. In addition, we discuss the timing of initiation of anticoagulation. In the second of a two-part review, we discuss the use of NOAC for stroke prevention in the following subgroups of patients with AF: (vii) secondary stroke prevention in patients after stroke or transient ischaemic attack (TIA), (viii) patients with acute stroke requiring thrombolysis or thrombectomy, (ix) those initiating or restarting OAC treatment after stroke or TIA, (x) those with renal impairment on dialysis, (xi) the elderly, (xii) those at high risk of gastrointestinal bleeding, and (xiii) those with hypertension. In addition, we discuss adherence and compliance. Finally, we present a summary of treatment suggestions. In specific subgroups of patients with AF, evidence supports the use of particular NOACs and/or particular doses of anticoagulant. The appropriate choice of treatment for these subgroups will help to promote optimal clinical outcomes.

Abstract 38: Comparison of Gastrointestinal Bleeding Risk Among Different Statin Exposures With Warfarin: An Electronic Health Record-based Retrospective Cohort Study

Introduction: Patients who require both warfarin and statin are frequently seen in vascular clinics. Gastrointestinal bleeding (GIB) is one of the most frequently occurring complications when a patient is administered warfarin, and this complication hinders continuous administration of warfarin. Hypothesis: GIB risk may differ among different statin exposures with warfarin. Methods: We observed patients who were exposed to one of four statins (pravastatin, simvastatin, atorvastatin, or rosuvastatin) and warfarin concomitantly for up to 2 years (730 days). Observation was ended when GIB occurred or observation was censored. To evaluate the risk of co-administration of different statins and warfarin on GIB, within-class comparison was used. We performed 1:1 matching using a propensity score for comparison of each single statin and others. Kaplan-Meier analysis with log-rank test and Cox proportional hazard regression were conducted for comparison. Results: We identified 1,686 patients who were administered statin concomitantly with warfarin. The patients were classified by each statin: 287 patients were exposed to pravastatin, 317 to simvastatin, 716 to atorvastatin, and 366 to rosuvastatin. Mean levels of total cholesterol during the observation period were 167 ± 44, 155 ± 36, 145 ± 35, and 139 ± 37 mg/dl, respectively (p&lt;0.001). On Kaplan-Meier curve analyses, GIB was less frequent in the pravastatin group than in others (p&lt;0.05). It was more frequent in the rosuvastatin group than in others (p=0.009). In the Cox proportional hazard regression analysis, age, sex, Charlson comorbidity index, nonsteroidal anti-inflammatory drug exposure, steroid exposure, antiplatelet exposure, and the proportion of time in the therapeutic range of warfarin international normalized ratio were adjusted. Hazard ratio (HR) of GIB on statin exposure in the rosuvastatin group was significantly high (HR, 5.0 [95% confidence interval, 1. 1-23.3], p=0.038) while the ratio in the pravastatin group tended to low (0.3 [0.1-1.0], p=0.051). Conclusions: Rosuvastatin administration has a relatively high risk of GIB among patients who are concomitantly administered warfarin, whereas pravastatin administration appears to carry a low risk.

Dabigatran in real-world atrial fibrillation. Meta-analysis of observational comparison studies with vitamin K antagonists.

In the RE-LY clinical trial, dabigatran presented a better effectiveness/safety profile when compared to warfarin. However, clinical trials are not very representative of the real-world setting. We aimed to assess the performance of dabigatran in real-world patients with atrial fibrillation (AF) by means of a systematic review and meta-analysis of observational comparison studies with vitamin K antagonists (VKA). We searched PubMed, Embase and Scopus databases until November 2015 and selected studies according to the following criteria: observational study performed with nonvalvular AF patients; reporting adjusted hazard ratios (HR) of clinical events in a follow-up period; for dabigatran 75 mg, 110 mg or 150 mg versus VKA. Twenty studies were selected which included 711,298 patients, 210,279 of which were treated with dabigatran and the remaining 501,019 with VKA. Ischaemic stroke incidence was of 1.65 /100 patient-years for dabigatran and 2.85/100 patient-years for VKA (HR 0.86, 95 % confidence interval of 0.74-0.99). Major bleeding rate was 3.93/100 patient-years for dabigatran and 5.61/100 patient-years for VKA (0.79, 0.69-0.89). Risk of mortality (0.73, 0.61-0.87) and intracranial bleeding (0.45, 0.38-0.52) were significantly lower in patients treated with dabigatran when compared to patients on VKA. Risk of gastrointestinal (GI) bleeding was significantly higher in patients treated with dabigatran (1.13, 1.00-1.28). No significant difference was observed in risk of myocardial infarction (0.99, 0.89-1.11). In this combined analysis of real-world observational comparison studies with VKA, dabigatran was associated with a lower risk of ischaemic stroke, major bleeding, intracranial bleeding and mortality, higher risk of GI bleeding and a similar risk of myocardial infarction.

Patients with Gastric Antral Vascular Ectasia (GAVE) Are at a Higher Risk of Gastrointestinal Bleeding in the Absence of Cirrhosis.

Background and Aims: Gastric antral vascular ectasia (GAVE) is commonly found in patients with cirrhosis, but it is also associated with other diseases in the absence of cirrhosis. Whether GAVE confers a different severity of gastrointestinal (GI) bleeding between patients with and without cirrhosis remains unknown. We aim to examine whether there is a difference in clinically significant GI bleeding due to GAVE in patients with or without cirrhosis. Methods: This is a retrospective case-control study of patients who were diagnosed with GAVE between January 2000 and June 2014. Patients were categorized into cirrhosis and noncirrhosis groups, and those with an additional GI bleeding source were excluded. Univariate comparisons and multivariable models were constructed using logistic regression. Results: In total, 110 patients diagnosed with GAVE on esophagogastroduodenoscopy (EGD) were included in our analysis; 84 patients had cirrhosis (76.4%) and 26 (23.6%) did not. Active GI bleeding was more prevalent in patients without cirrhosis (63.4% vs. 32.1%, p=0.003) despite similar indications for EGD, and endoscopic treatment with argon plasma coagulation (APC) was required more often in this group, approaching statistical significance (27% vs. 10.7%, p=0.056). There was no difference in bleeding severity, as evidenced by similar re-bleeding rates, surgery, or death attributed to uncontrolled bleeding. The strongest independent risk factor for GI bleeding was the absence of cirrhosis (odds ratio (OR): 5.151 (95% confidence interval (CI): 1.08-24.48, p=0.039). Conclusions: Patients with GAVE in the absence of cirrhosis are at higher risk for active GI bleeding and require more frequent endoscopic treatment than similar patients with cirrhosis. It may be worthwhile to treat GAVE in this population even in the absence of active bleeding.

Effectiveness and Safety of New and Traditional Oral Anticoagulants in a Population-Based Cohort of New Users with Atrial Fibrillation

To compare the effectiveness and safety of oral anticoagulants (OACs) -NOAC and VKA- in patients with atrial fibrillation (AF) in real-world clinical practice. Retrospective population-based cohort study. All new users of OAC from Nov2011 to Feb2014 with AF were included (N=21841). Data were obtained by linking diverse electronic databases of the Valencia Region, Spain. Incidence rates were estimated. Cox proportional hazards models adjusted for sociodemographic, clinical, healthcare use data, and propensity scores assessed the risk of several outcomes on effectiveness and safety of each NOAC compared with acenocumarol. Apixaban and warfarin patients were excluded because of few person-time observations The incidence of ischemic stroke was 12.5, 8.7 and 10.8 per 1000 person-years for acenocumarol, dabigatran and rivaroxaban. After adjustment no differences were found for NOAC in the risk of ischemic stroke compared to acenocumarol (HR:0.78, 95%CI:0.51-1.20 for dabigatran; HR:0.76, 95%CI:0.42-1.35 for rivaroxaban). Regarding the incidence of mortality (80.2, 65.1 and 91.7, respectively) no increased risk was found (HR:0.96, 95%CI:0.81-1.12 for dabigatran; HR: 1.16, 95%CI:0.95-1.42 for rivaroxaban). The incidence of gastrointestinal bleeding was 18.3, 21.4 and 14.4, respectively, being dabigatran associated with a higher risk (HR:1.44, 95%CI:1.08-1.92) but not rivaroxaban (HR: 0.72, 95%CI: 0.43-1.19). However, no differences were found for major gastrointestinal bleeding (HR: 1.01, 95%CI: 0.59-1.73 for dabigatran; HR:0.43, 95%CI:0.16-1.17 for rivaroxaban). Regarding the incidence of intracranial haemorrhage (8.8, 3.0 and 5.4, respectively), dabigatran was found to be associated with a decreased risk (HR:0.36, 95%CI:0.18-0.74), and no differences for rivaroxaban (HR: 0.56, 95%CI 0.25-1.27). NOAC were not associated with an increased risk of stroke or death compared with acenocumarol among newly treated patients with AF. Dabigatran was associated with lower risk of intracranial haemorrhage and higher risk of gastrointestinal bleeding. The risk of major gastrointestinal bleeding related to NOAC was similar to that for acenocumarol.

Efficacy and Harms of Direct Oral Anticoagulants in the Elderly for Stroke Prevention in Atrial Fibrillation and Secondary Prevention of Venous Thromboembolism: Systematic Review and Meta-Analysis.

Evidence regarding the use of direct oral anticoagulants (DOACs) in the elderly, particularly bleeding risks, is unclear despite the presence of greater comorbidities, polypharmacy, and altered pharmacokinetics in this age group. We performed a systematic review and meta-analysis of randomized trials of DOACs (dabigatran, apixaban, rivaroxaban, and edoxaban) for efficacy and bleeding outcomes in comparison with vitamin K antagonists (VKA) in elderly participants (aged ≥75 years) treated for acute venous thromboembolism or stroke prevention in atrial fibrillation. Nineteen studies were eligible for inclusion, but only 11 reported data specifically for elderly participants. The efficacy in managing thrombotic risks for each DOAC was similar or superior to VKA in elderly patients. A nonsignificantly higher risk of major bleeding than with VKA was observed with dabigatran 150 mg (odds ratio, 1.18; 95% confidence interval, 0.97-1.44) but not with the 110-mg dose. Significantly higher gastrointestinal bleeding risks with dabigatran 150 mg (1.78, 1.35-2.35) and dabigatran 110 mg (1.40, 1.04-1.90) and lower intracranial bleeding risks than VKA for dabigatran 150 mg (0.43, 0.26-0.72) and dabigatran 110 mg (0.36, 0.22-0.61) were also observed. A significantly lower major bleeding risk in comparison with VKA was observed for apixaban (0.63, 0.51-0.77), edoxaban 60 mg (0.81, 0.67-0.98), and 30 mg (0.46, 0.38-0.57), whereas rivaroxaban showed similar risks. DOACs demonstrated at least equal efficacy to VKA in managing thrombotic risks in the elderly, but bleeding patterns were distinct. In particular, dabigatran was associated with a higher risk of gastrointestinal bleeding than VKA. Insufficient published data for apixaban, edoxaban, and rivaroxaban indicate that further work is needed to clarify the bleeding risks of these DOACs in the elderly. http://www.crd.york.ac.uk/PROSPERO. Unique identifier: PROSPERO CRD42014007171/.

Pharmacological interventions for prevention and treatment of upper gastrointestinal bleeding in newborn infants

Background Upper gastrointestinal bleeding is typically a mild, self-limiting condition that can affect both preterm and term neonates, although it can be severe particularly when associated with co-morbidities. Pharmacological interventions with a proton pump inhibitor (PPI), H2 receptor antagonist (H2RA), antacid, bismuth and sucralfate may have effects on both the prevention and treatment of upper gastrointestinal bleeding in infants. Objectives To assess how different pharmacological interventions (PPIs, H2RAs, antacids, sucralfate or bismuth salts) administered to preterm and term neonates for the prevention or treatment of upper gastrointestinal bleeding to reduce morbidity and mortality compare with placebo or no treatment, supportive care, or each other. Search methods We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2018, Issue 6), MEDLINE via PubMed (1966 to 12 July 2018), Embase (1980 to 12 July 2018), and CINAHL (1982 to 12 July 2018). We also searched clinical trial databases, conference proceedings, the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials, and online for Chinese literature articles. Selection criteria We selected randomised, quasi-randomised and cluster-randomised trials involving preterm and term neonates. Trials were included if they used a proton pump inhibitor, H2 receptor antagonist, antacid, sucralfate or bismuth either for the prevention or treatment of upper gastrointestinal bleeding. Data collection and analysis Two review authors independently assessed the eligibility of studies for inclusion, extracted data and assessed methodological quality. We conducted meta-analysis using a fixed-effect model. We used the GRADE approach to assess quality of evidence. Main results Eleven studies with 818 infants met the criteria for inclusion in this review.Four trials with 329 infants assessed the use of an H2 receptor antagonist for prevention of upper gastrointestinal bleeding in high-risk newborn infants. Meta-analysis of these four trials identified a reduction in any upper gastrointestinal bleeding when using an H2 receptor antagonist (typical risk ratio (RR) 0.36, 95% confidence interval (CI) 0.22 to 0.58; typical risk difference (RD) -0.20, 95% CI -0.28 to -0.11; number needed to treat for an additional beneficial outcome (NNTB) 5, 95% CI 4 to 9). The quality of evidence was moderate. A single trial with 53 infants assessing prevention of upper gastrointestinal bleeding reported no difference in mortality in infants assigned H2 receptor antagonist versus no treatment; however the quality of evidence was very low.Seven trials with 489 infants assessed an inhibitor of gastric acid (H2 receptor antagonist or proton pump inhibitor) for treatment of gastrointestinal bleeding in newborn infants. Meta-analysis of two trials (131 infants) showed no difference in mortality from use of a H2 receptor antagonist compared to no treatment. The quality of evidence was low. Meta-analysis of two trials (104 infants) showed a reduction in duration of upper gastrointestinal bleeding from use of an inhibitor of gastric acid compared to no treatment (mean difference -1.06 days, 95% CI -1.28 to -0.84). The quality of evidence was very low. Meta-analysis of six trials (451 infants) showed a reduction in continued upper gastrointestinal bleeding from use of any inhibitor of gastric acid compared to no treatment (typical RR 0.36, 95% CI 0.26 to 0.49; typical RD -0.26, 95% CI -0.33, -0.19; NNTB 4, 95% CI 3 to 5). The quality of evidence was low. There were no significant subgroup differences in duration of upper gastrointestinal bleeding or of continued upper gastrointestinal bleeding according to type of inhibitor of gastric acid. A single trial (38 infants) reported no difference in anaemia requiring blood transfusion from use of a H2 receptor antagonist compared to no treatment.Although no serious adverse events were reported from the use of a H2 receptor antagonist or proton pump inhibitor, some neonatal morbidities - including necrotising enterocolitis, ventilator-associated pneumonia, duration of ventilation and respiratory support, and duration of hospital stay - were not reported. Long-term outcome was not reported. Authors' conclusions There is moderate-quality evidence that use of an H2 receptor antagonist reduces the risk of gastrointestinal bleeding in newborn infants at high risk of gastrointestinal bleeding. There is low-quality evidence that use of an inhibitor of gastric acid (H2 receptor antagonist or proton pump inhibitor) reduces the duration of upper gastrointestinal bleeding and the incidence of continued gastric bleeding in newborn infants with gastrointestinal bleeding. However, there is no evidence that use of an inhibitor of gastric acid in newborn infants affects mortality or the need for blood transfusion. As no study reported the incidence of necrotising enterocolitis, ventilator- or hospital-associated pneumonia, sepsis, or long-term outcome, the safety of inhibitors of gastric acid secretion is unclear.