Aspirin Dose, Not Duration, May Raise GI Bleeding Risk

Background: In-hospital stroke (IHS) may differ from out-of-hospital stroke (OHS) in terms of mechanism, risk factors and outcomes. Objective/Hypothesis: We compared IHS and OHS treated with systemic or intra-arterial thrombolysis from a large national cohort in a cross-sectional study to further clarify these differences. Our hypothesis was that there would be poorer patient outcomes associated with IHS than OHS. Methods: Nationwide inpatient sample (NIS) for years 2005-2009 was searched for stroke cases treated with thrombolysis by using International Classification of Diseases-9 codes. Patients treated on the day of admission were classified as OHS. Primary outcome measures were inpatient mortality and functional independence at discharge as indicated by discharge to home (self-care). Secondary outcomes included intracranial hemorrhage (ICH), GI bleeding, tracheostomy and gastrostomy tube placement. IHS as an independent predictor of outcomes was studied using multivariate logistic regression. Results: IHS comprised of 1,054 (11.3%) cases of all (N=9,353) thrombolysed ischemic strokes. IHS was associated with higher co-morbidity profile and higher rates of acute medical conditions. In unadjusted analyses, IHS had higher inpatient mortality (18.8% vs. 10.9%, p<0.001) and lower rate of functional independence at discharge (21.7 vs. 28.6%, p<0.001). While IHS had higher rates of GI bleeding, tracheostomy and gastrostomy, the rate of ICH in IHS was similar to that of OHS (4.6% vs. 4.8%, p=0.807). After controlling for demographics, hospital characteristics and co-morbidities, inpatient mortality (adj. OR:1.82; 95% CI:1.53-2.16, p<0.001) and favorable discharge outcome (adj. OR:0.80; 95% CI:0.68-0.94, p=0.007)) remained significantly worse in IHS while the rate of ICH (adj. OR:0.91; 95% CI:0.67-1.23) remained similar to that of OHS. Conclusions: Thrombolysis in IHS is associated with worse outcomes and higher rates of inpatient medical complications compared to OHS, likely due to their higher co-morbidities and additional medical reasons for hospital admission. In spite of presumed higher bleeding risk in IHS, thrombolytic use is not associated with higher rate of ICH among IHS.

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Abstract 53: Ablation of Thrombin Signaling in Platelets but Not in Endothelial Cells Impairs Hemostasis in a Mouse Model of Spontaneous Gastrointestinal Bleeding

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.37.suppl_1.53 ◽

2017 ◽

Vol 37 (suppl_1) ◽

Author(s):

Stephen J Wilson ◽

Maria M Stevens ◽

Shaun R Coughlin

Keyword(s):

Myocardial Infarction ◽

Endothelial Cells ◽

Platelet Activation ◽

Bleeding Risk ◽

Arterial Disease ◽

Gi Bleeding ◽

Intestinal Polyposis ◽

Wild Type ◽

Spontaneous Bleeding ◽

Peripheral Arterial

Human PAR1 is expressed in endothelial cells as well as in platelets where it facilitates the response to thrombin and platelet activation. Vorapaxar, a PAR1 antagonist, prevents myocardial infarction and stroke in patients with prior MI or peripheral arterial disease at a cost of increased bleeding risk. Par1 is also highly expressed in endothelial cells in mice, and Par1-deficiency is associated with bleeding in the mouse embryo at midgestation. Additionally, known actions of endothelial PAR1 activation suggest pro-hemostatic functions. This raises the question of whether inhibition of PAR1 function in endothelial cells (in addition to PAR1 inhibition in platelets) contributes to the bleeding risk associated with Vorapaxar treatment. Our previous work demonstrated that Par1 deficiency results in loss of thrombin signaling in mouse endothelial cells but not mouse platelets, while Par4 deficiency ablated thrombin-induced platelet activation in mice. Thus, mice allow us to separate loss of thrombin signaling in platelets from loss of thrombin signaling in endothelial cells. Accordingly, we used Apc min/+ mice, which develop intestinal polyposis and spontaneous GI bleeding, as a model to determine whether loss of thrombin signaling in platelets (Par4 KO) or endothelial and other cells (Par1 KO) exacerbates spontaneous bleeding. Hematocrit and other hematologic parameters were measured biweekly from 7 weeks through 15 weeks of age. Hematocrits in mice wild-type for Apc were stable over this period (41.48 ± 0.48 at 7 weeks; 40.48 ± 0.37 at 15 weeks, n=15). Hematocrits in Apc min/+ mice fell approximately linearly from 37.06 ± 0.82 at 7 weeks to 14.39 ± 1.12 at 15 weeks (n=15). Hematocrits in Par1-deficient Apc min/+ mice were indistinguishable from those in Apc min/+ without Par deficiency (14.39 ± 1.12 vs 14.47 ± 1.66 at 15 weeks; n=6-15). By contrast, Par4-deficient Apc min/+ mice were already severely anemic at 7 weeks compared to Apc min/+ mice (19 ± 2.0 vs 39 ± 3.6; p<0.01, n=4). Par-dependent differences in polyp count and size were not detected. Taken together, our results suggest that loss of thrombin signaling in platelets promotes spontaneous GI bleeding in the Apc min model while loss of thrombin signaling in endothelial cells is without effect in this system.

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Abstract 140: Comparison of Major Complication of Oral Anticoagulants in Non-Valvular Atrial Fibrillation: Systematic Review and Meta-Analyses

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.37.suppl_1.140 ◽

2017 ◽

Vol 37 (suppl_1) ◽

Author(s):

Hong Seok Lee

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Major Bleeding ◽

Oral Anticoagulant ◽

Stroke Risk ◽

Oral Anticoagulants ◽

Bleeding Risk ◽

Gi Bleeding ◽

Ischemic Stroke Risk ◽

Meta Analyses

Background: Oral anticoagulants known as a novel oral anticoagulant have been used for the management of non -valvular atrial fibrillation. There was no enough study regarding the efficacy and safety of three major new oral anticoagulants. We assessed major three oral anticoagulants in terms of major bleeding complication and stroke prevention by meta-analyses studies comparing those drugs. Method: Relevant studies were identified through electronic literature searches of MEDLINE, EMBASE, Cochrane library, and clinicaltrials.gov (from inception to February 24, 2016). RevMan and ITC software were used for direct comparisons, respectively. Results: Apixaban (N=6020), versus dabigatran(N=12038), apixaban versus rivaroxaban(N=8503) and rivaroxaban versus dabigatran were analyzed directly. There was significantly higher major bleeding risks in apixaban compared to dabigatran (both 110mg and 150mg) after adjusting baseline bleeding risk (Relative risk 3.41, 95% confidence interval(2.61 to 4.47) in 110mg, (5.62, 4.83 to 6.54) in 150mg. Intracranial bleeding risk in apixaban was significantly higher than in dabigatran (10.5, 6.10 to18.01). However, apixaban had less GI bleeding risk compared to dabigatran (0.80 , 0.65 to 0.98) and also had less ischemic stroke risk (0.31,0.22 to 0.42). Rivaroxaban showed higher major bleeding risk than dabigatran 110mg (2.34 , 1.81 to 3.03), however, Rivaroxaban had less bleeding risk compared to dabigatran 150mg (0.41, 0.35 to 0.46). Dabigatran 110mg and 150mg had less GI bleeding risk compared to rivaroxaban (0.31 , 0.24 to 0.39) and (0.23,0.17 to 0.29) respectively. Ischemic stroke risk was also decreased in dabigatran110mg (0.46, 0.38 to 0.57). and 150mg (0.66 ,0.52 to 0.83). Conclusion: Observed oral anticoagulants were associated with various complications. Overall, apixaban had higher intracranial bleeding risk than dabigatran. The highest GI bleeding risk in rivaroxaban compared to apixaban and dabigatran. Ischemic stroke risk was the highest in dabigatran. In conclusion, we may use those oral anticoagulant based on risks rates, however, a larger study with longer follow-up is needed to corroborate findings.

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Major GI bleeding in older persons using aspirin: incidence and risk factors in the ASPREE randomised controlled trial

Gut ◽

10.1136/gutjnl-2020-321585 ◽

2020 ◽

pp. gutjnl-2020-321585 ◽

Cited By ~ 3

Author(s):

Suzanne E Mahady ◽

Karen L Margolis ◽

Andrew Chan ◽

Galina Polekhina ◽

Robyn L Woods ◽

...

Keyword(s):

Risk Factors ◽

Randomised Controlled Trial ◽

Absolute Risk ◽

Controlled Trial ◽

Bleeding Risk ◽

The Elderly ◽

Community Dwelling ◽

Gi Bleeding ◽

Prophylactic Use ◽

Randomised Controlled

ObjectiveThere is a lack of robust data on significant gastrointestinal bleeding in older people using aspirin. We calculated the incidence, risk factors and absolute risk using data from a large randomised, controlled trial.DesignData were extracted from an aspirin versus placebo primary prevention trial conducted throughout 2010–2017 (‘ASPirin in Reducing Events in the Elderly (ASPREE)’, n=19 114) in community-dwelling persons aged ≥70 years. Clinical characteristics were collected at baseline and annually. The endpoint was major GI bleeding that resulted in transfusion, hospitalisation, surgery or death, adjudicated independently by two physicians blinded to trial arm.ResultsOver a median follow-up of 4.7 years (88 389 person years), there were 137 upper GI bleeds (89 in aspirin arm and 48 in placebo arm, HR 1.87, 95% CI 1.32 to 2.66, p<0.01) and 127 lower GI bleeds (73 in aspirin and 54 in placebo arm, HR 1.36, 95% CI 0.96 to 1.94, p=0.08) reflecting a 60% increase in bleeding overall. There were two fatal bleeds in the placebo arm. Multivariable analyses indicated age, smoking, hypertension, chronic kidney disease and obesity increased bleeding risk. The absolute 5-year risk of bleeding was 0.25% (95% CI 0.16% to 0.37%) for a 70 year old not on aspirin and up to 5.03% (2.56% to 8.73%) for an 80 year old taking aspirin with additional risk factors.ConclusionAspirin increases overall GI bleeding risk by 60%; however, the 5-year absolute risk of serious bleeding is modest in younger, well individuals. These data may assist patients and their clinicians to make informed decisions about prophylactic use of aspirin.Trial registration numberASPREE. NCT01038583.

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Mo1276 – No Differences in Gi Bleeding Risk Between Clopidogrel-, Ticagrelor- Or Prasugrel- Based Dual Antiplatelet Therapy After Percutaneous Coronary Intervention

Gastroenterology ◽

10.1016/s0016-5085(19)38791-8 ◽

2019 ◽

Vol 156 (6) ◽

pp. S-743

Author(s):

Viviana Laredo ◽

Sandra Garcia ◽

Nuria Saura ◽

Maria Hernandez Ainsa ◽

Patricia Carrera ◽

...

Keyword(s):

Percutaneous Coronary Intervention ◽

Antiplatelet Therapy ◽

Dual Antiplatelet Therapy ◽

Bleeding Risk ◽

Coronary Intervention ◽

Gi Bleeding ◽

Percutaneous Coronary

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COX-2 inhibitors: lower GI bleeding risk but population risk increased?

Reactions Weekly ◽

10.2165/00128415-200410020-00005 ◽

2004 ◽

Vol &NA; (1002) ◽

pp. 3

Author(s):

&NA;

Keyword(s):

Bleeding Risk ◽

Gi Bleeding ◽

Lower Gi Bleeding ◽

Cox 2 ◽

Cox 2 Inhibitors

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Association between Renal Function and Bleeding Risk for Dabigatran after Switching from Warfarin

American Journal of Nephrology ◽

10.1159/000446848 ◽

2016 ◽

Vol 44 (1) ◽

pp. 11-18 ◽

Cited By ~ 3

Author(s):

Roberto S. Kalil ◽

Peter J. Kaboli ◽

Xin Liu ◽

Mary Vaughan-Sarrazin

Keyword(s):

Renal Function ◽

Healthcare Providers ◽

Bleeding Risk ◽

Bleeding Complications ◽

Close Monitoring ◽

Gi Bleeding ◽

Bleeding Events ◽

National Patient ◽

Study Population ◽

The Impact

Background: There is a higher risk of gastrointestinal (GI) bleeding in patients treated with dabigatran versus warfarin. We analyzed the impact of renal function on the relative risk of bleeding in patients converted to dabigatran. Methods: Patients aged ≥65 years who received anticoagulation with warfarin for a minimum of 6 months and subsequently converted to dabigatran or remained on warfarin were studied. Data sources included VA National Patient Care, and VA Decision Support System National Pharmacy and Laboratory. Each patient who converted to dabigatran 150 mg twice daily was matched by propensity score with 2 patients on warfarin who did not convert. Outcomes included rates of hospital admission for GI or other major bleeding and mortality, stratified by estimated glomerular filtration rate (eGFR). Results: Study population included 864 patients who converted and 1,710 patients who did not convert to dabigatran. In patients with eGFR 50-80 ml/min/1.73 m², the hazard of GI bleeding in patients who initiated dabigatran was nearly 3 times higher, (4.1 vs. 1.3 per 100 patient years; hazards ratio 2.94; 95% CI 1.24-7.02; p = 0.015), compared to patients who remained on warfarin. There were relatively few patients with eGFR <50 or >80 ml/min/1.73 m2, and relatively few bleeding events outside the GI tract. Conclusions: Prescribing healthcare providers should exercise caution and close monitoring for bleeding complications when converting from warfarin to dabigatran, even in patients with renal function in the range considered safe for dabigatran use as per current recommendations.

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