Risk Of Overall Bleeding Research Articles

Direct oral anticoagulants vs Vitamin-K antagonists in solid organ transplant recipients: A systematic review and meta-analysis.

Oure review aimed to examine evidence on the safety and efficacy of direct oral anticoagulants (DOAC) vs Vitamin K antagonists (VKA) in patients with solid organ transplants. PubMed, Embase, and Web of Science libraries were searched from inception to 25th November 2023 for all studies comparing DOAC with VKA in solid organ recipients. Nine studies were included with patients who had undergone kidney, heart, or liver transplants. Meta-analysis showed that patients receiving DOAC had a significantly reduced risk of composite bleeding as compared to those with VKA (RR: 0.45 95% CI: 0.30, 0.68 I2=25%). However, the risk of major bleeding was not significantly different between the two groups (RR: 0.76 95% CI: 0.40, 1.42 I2=37%). Pooled analysis showed that the risk of VTE (RR: 0.90 95% CI: 0.72, 1.13 I2=0%) and ischemic stroke (RR: 0.87 95% CI: 0.39, 1.94 I2=12%) was not significantly different between DOAC and VKA groups. Limited data shows that DOAC are safe and effective in patients with solid organ transplants. The overall risk of bleeding may be reduced with the use of DOAC. There is a need for randomized controlled trials comparing DOAC and VKA in such patients to obtain high-quality evidence.

A retrospective analysis of anticoagulant safety among heart transplant recipients undergoing endomyocardial biopsy.

Transvenous endomyocardial biopsy is an invasive procedure which is used to diagnose rejection following an orthotopic heart transplant. Endomyocardial biopsy is widely regarded as low risk with all-cause complication rates below 5% in most safety studies. Following transplant, some patients require therapeutic anticoagulation. It is unknown whether anticoagulation increases endomyocardial biopsy bleeding risk. Records from 2061 endomyocardial biopsies performed for post-transplant rejection surveillance at our institution between November 2016 and August 2022 were reviewed. Bleeding complications were defined as vascular access-related hematoma or bleeding, procedure-related red blood cell transfusion, and new pericardial effusion. Relative risk and small sample-adjusted 95% confidence interval was calculated to investigate the association between bleeding complications and anticoagulation. The overall risk of bleeding was 1.2% (25/2061 cases). There was a statistically significant increase in bleeding among patients on intravenous (RR 4.46, CI 1.09-18.32) but not oral anticoagulants (RR .62, CI .15-2.63) compared to patients without anticoagulant exposure. There was a trend toward increased bleeding among patients taking warfarin with INR ≥ 1.8 (RR 3.74, CI .90-15.43). Importantly, no bleeding events occurred in patients taking direct oral anticoagulants such as apixaban. Based on these results, intravenous rather than oral anticoagulation was associated with a significantly higher risk of bleeding complications following endomyocardial biopsy.

Impact of type of anticoagulant on clinical outcomes in cancer patients who had atrial fibrillation

To date, evidence on optimal anticoagulant options in patients with AF who concurrently have active cancer remains elusive. To describe anticoagulant patterns and clinical outcomes among patients with a concomitant diagnosis of AF and cancer. Data were obtained from the University of Utah and Huntsman Cancer Institute (HCI) Hospitals. Patients were included if they had diagnosis of AF and cancer. Outcome was type and pattern of anticoagulant. Clinical outcomes were stroke, bleeding and all-cause mortality. From October 1999 to December 2020, there were 566 AF patients who concurrently had active cancer. Mean age ± standard deviation was 76.2 ± 10.7 and 57.6% were males. Comparing to warfarin, patients who received direct oral anticoagulant (DOACs) were associated with similar risk of stroke (adjusted hazard ratio, aHR 0.8, 95% confidence interval [CI] 0.2–2.7, P = 0.67). On contrary, those who received low-molecular-weight heparin (LMWH) were associated with significantly higher risk of stroke comparing to warfarin (aHR 2.4, 95% CI 1.0–5.6, P = 0.04). Comparing to warfarin, DOACs and LMWH was associated with similar risk of overall bleeding with aHR 1.1 (95% CI 0.7–1.6, P = 0.73) and aHR 1.1 (95% CI 0.6–1.7, P = 0.83), respectively. Patients who received LMWH but not DOACs were associated with increased risk of death as compared to warfarin, aHR 4.5 (95% CI 2.8–7.2, P < 0.001) and 1.2 (95% CI 0.7–2.2, P = 0.47). In patients with active cancer and AF, LMWH, compared to warfarin, was associated with an increased risk of stroke and all-cause mortality. Furthermore, DOACs was associated with similar risk of stroke, bleeding and death as compared to warfarin.

Transhepatic versus transperitoneal approach in percutaneous cholecystostomy: a meta-analysis

To determine whether the transhepatic or transperitoneal approach is the optimal percutaneous cholecystostomy approach. A systematic review and meta-analysis was undertaken in which the Medline, EMBASE, and PubMed databases were searched for studies that compared both approaches in patients undergoing percutaneous cholecystostomy. Statistical analysis of dichotomous variables was carried out using odds ratio as the summary statistic. Four studies totalling 684 patients (396 [58%] males, mean age 74 years) who had undergone percutaneous cholecystostomy via the transhepatic (n=367) and transperitoneal (n=317) approach were analysed. Although the overall risk of bleeding was low (4.1%), it was significantly higher in the transhepatic approach compared with the transperitoneal approach (6.3% versus 1.6% respectively, odds ratio=4.02 [1.56, 10.38]; p=0.004). There were no significant differences in pain, bile leak, tube-related complications, wound infection, or abscess formation between the approaches. Percutaneous cholecystostomy can be performed safely and successfully via the transhepatic and transperitoneal approaches. Although the overall rate of bleeding was significantly higher with the transhepatic approach, there were confounding factors due to technical differences between the studies. The small number of the included studies, in addition to variability of the definitions of outcomes, imposed other limitations. Further large-volume cases series and ideally a randomised trial with well-defined outcomes are required to confirm these findings.

Risk of Bleeding with Endoscopic Ultrasound-Guided Tissue Acquisition in Patients on Antithrombotic Therapy: A Systematic Review and Meta-Analysis.

The present guidelines stratify endoscopic ultrasound-guided tissue acquisition (EUS-TA) as a high-bleeding risk procedure in patients on antithrombotics. However, the data regarding the same are conflicting. Therefore, this meta-analysis aimed to analyze the bleeding event rates associated with EUS-TA in patients receiving antithrombotic therapy. A literature search from January 2000 to August 2022 was done for studies on EUS-guided TA in patients receiving antithrombotics. The primary outcome was incidence of overall and major bleeding. Pooled event rates across studies were expressed with summative statistics. A total of 12 studies were included in the meta-analysis. The pooled risk of overall bleeding and major bleeding in patients on antithrombotics was 2.0% (0.6-3.4) and 0.8% (0.0-1.6), respectively. In patients taking thienopyridine or anticoagulants, the pooled risk of overall bleeding and major bleeding was 2.4% (0.9-3.9) and 1.7% (0.4-3.1), respectively. Patients on antithrombotics had a higher odd of overall bleeding (OR 2.12, 1.20-3.83) and major bleeding (OR 3.58, 1.11-11.52) compared to controls. The odds of overall bleeding (OR 0.95, 95%CI 0.38-2.42) and major bleeding (OR 1.57, 95%CI 0.45-5.54) were comparable between patients on antithrombotics who continued and those who discontinued it preprocedural. Despite an increase risk of bleeding with EUS-TA in patients on antithrombotics, the pooled incidence remains low. Compared to the previous guidelines stating thienopyridine use as high risk for bleeding, the present analysis showed a bleeding rate of less than 1%. Discontinuing antithrombotics prior to EUS-TA does not reduce the bleeding risk significantly, requiring strict monitoring.

Anticoagulation treatment for patients with coronavirus disease 2019 (COVID-19) and its clinical effectiveness in 2020: A meta-analysis study.

Background:To better inform efforts to treat and control the current outbreak with effective anticoagulant treatment strategies for coronavirus disease 2019 patients.Methods:We searched Cochrane Library, Pubmed, EMBASE, MEDLINE, SCIEXPANDED, Web of Science, Google Scholar, CNKI (Chinese Database), WanFang (Chinese Database), CBM (Chinese Database), VIP (Chinese Database) for studies published from November 1, 2019 to October 1, 2020, and we searched references of identified articles. Studies were reviewed for methodological quality. A random-effects model was used to pool results. Heterogeneity was assessed using I2. Publication bias was assessed using funnel plot.Results:Fourteen studies involving 7681 patients were included. We meta-analyzed the bleeding, deep vein thrombosis, and pulmonary embolism risk between no anticoagulation and prophylactic anticoagulation, and found no significant difference. The same trend occurred in the comparison between with and without anticoagulation. However, when compared with no anticoagulation, both prophylactic anticoagulation (odd ratio [OR] = 0.80, 95% confidence interval [CI]: 0.69–0.93) and therapeutic anticoagulation (OR = 0.91, 95% CI: 0.80–1.05) had lower risk of mortality. Furthermore, the risk of overall bleeding among patients with therapeutic anticoagulation was 3.11 times (95% CI: 2.29–4.24) than that of patients with prophylactic anticoagulation. On the contrary, therapeutic anticoagulation had lower risk of deep vein thrombosis than prophylactic anticoagulation (OR = 0.34, 95% CI: 0.19–0.63).Conclusions:Among coronavirus disease 2019 patients, preventive and therapeutic anticoagulation were more beneficial than no anticoagulation for reducing mortality rate. The result will inform healthcare providers and public health policy makers in efforts to treat and control the current outbreak.

Impact of anticoagulation on recurrent thrombosis and bleeding after hematopoietic cell transplantation.

History of venous thromboembolism (VTE) is prevalent among patients undergoing hematopoietic cell transplantation (HCT). Management of anticoagulation is particularly challenging as most patients will have chemotherapy-induced thrombocytopenia while awaiting engraftment post-HCT. We conducted a retrospective study of autologous and allogeneic HCT recipients with prior VTE from 2006-2015 to 1) compare anticoagulant strategies on short-term VTE recurrence and bleeding and 2) assess predictors for VTE recurrence beyond 30 days. Patients with VTE were allocated to two cohorts based on anticoagulant strategy at thrombocytopenia onset and underwent inverse probability weighting to assess primary outcomes of VTE recurrence and bleeding within 30 days post-HCT. Subsequently, multivariable logistic regression model was used to assess the association of 100-day VTE recurrence by the HIGH-2-LOW VTE risk assessment score and whether patients resumed anticoagulation at platelet recovery. Thirteen percent of recipients had VTE prior to HCT; of those meeting inclusion criteria, 227 continued anticoagulation and 113 temporarily discontinued it. Anticoagulant strategy was not significantly associated with decreased risk of VTE recurrence within 30 days (3% vs 4%, p=0.61); however, risk of overall bleeding was non-significantly higher in those who continued vs discontinued anticoagulation (41% vs 31%, p=0.08). In a subgroup of 250 allogeneic HCT patients, every one-point increase of HIGH-2-LOW score was significantly associated with VTE recurrence at 100 days (OR 1.57 [95% CI 1.10-2.23]), while anticoagulation resumption upon platelet engraftment was associated with lower recurrent risk (OR 0.48 [0.20-1.14]). Temporarily withholding anticoagulation during thrombocytopenia may optimize risk-benefit tradeoffs, though additional strategies are essential to prevent VTE recurrence after hematopoietic recovery.

The Effects of Oral Anticoagulant Exposure on the Surgical Outcomes of Patients Undergoing Surgery for High-Risk Abdominal Emergencies

BackgroundIn chronic anticoagulant users undergoing surgery, bleeding and thromboembolism are common and serious complications. Many studies on mainly elective or minor emergency surgical procedures with low associated risks have focused on these outcomes. In comparison, patients undergoing high-risk emergency abdominal surgical procedures have not received sufficient attention. This study aimed to compare outcomes between oral anticoagulant users and nonusers who required emergency laparotomy for high-risk abdominal emergencies. MethodsPatients who underwent surgery for abdominal emergencies at our institution between January 2012 and July 2019 were retrospectively reviewed. ResultsThere were 875 patients, including 370 anticoagulant users and 505 nonusers. Of the 370 anticoagulant users, 189 (51.3), 77 (20.8%), 45 (12.2%), and 59 (15.9%) were prescribed antiplatelets, a vitamin k antagonist, a direct oral anticoagulant, and a combination drug regimen, respectively. The most common high-risk emergencies requiring surgery in both groups were perforated viscus (25.7% vs 40.9%), mesenteric ischemia with enteric necrosis (27% vs 12.8%), and bowel obstruction (17.6% vs 28.1%). The overall bleeding rate was higher (29.2% vs 22%, p = 0.015) in anticoagulant users than in nonusers, but the major bleeding rate was similar (17.8% vs 14.1%, p = 0.129) between the two groups. The rates of thromboembolic events and mortality were significantly higher in anticoagulant users than in nonusers (25.7% vs 9.7%, p < 0.0001 and 39.7% vs 31.1%, p = 0.01, respectively). Liver cirrhosis, peripheral arterial diseases, reoperation, and blood product transfusion were independent predictors of the overall risk of bleeding or TEEs, according to the multivariate analysis. In this model, liver cirrhosis had the largest overall effect on mortality, followed by pneumonia, thromboembolism, peripheral arterial disease, blood product transfusion, and atrial fibrillation. The use of oral anticoagulants was not an independent predictor of either bleeding or in-hospital mortality. The use of oral anticoagulants was associated with a decreased risk of all-cause in-hospital mortality. ConclusionBased on our results, the continued use of oral anticoagulants is more protective than harmful considering the overall outcomes in this subset of patients.

ERCP-Related Bleeding

Clinically significant bleeding is an uncommon complication of diagnostic endoscopic retrograde cholangiopancreatography. But the endoscopists needs to be skilled at prevention and management. Post ERCP bleeding is most often seen following sphincterotomy. The overall risk of bleeding in patients undergoing sphincterotomy is approximately 1-2 percent. Most bleeding episodes are mild to moderate in severity. The risk of bleeding can be minimized by identifying patients at risk, correcting coagulation abnormalities and careful technique by skilled endoscopists in high-volume centers. Post-sphincterotomy bleeding often stops spontaneously and is rarely life-threatening, except in patients with a bleeding diathesis. Most clinically relevant bleedings can be managed with medical treatment and/or endoscopic therapy, which should be performed without delay in patients who have immediate bleeding. Endoscopic therapy options include epinephrine injection, hemostatic clips, thermal therapy and placement of full covered self-expandable metal stents. Angiography or surgery is usually reserved for patients with refractory bleeding and is rarely required.

Abstract 15740: Concomitant Use of Dronedarone and Direct Oral Anticoagulants and Risk of Bleeding in Patients With Atrial Fibrillation: An Analysis of the U.S. Truven Health MarketScan Database

Introduction: Dronedarone (DR), a P-gp and CYP 3A4 inhibitor may increase exposure and the risk of bleeding when combined with direct oral anticoagulants (DOACs). Objective: To examine the association between concomitant use of DR and the DOACs, apixaban (A), dabigatran (D), and rivaroxaban (R), and risk of bleeding compared to DOAC monotherapy in patients with atrial fibrillation (AF). Methods: A retrospective cohort study using a U.S. claims database, Truven Health MarketScan identified new users of A, D, and R in patients with AF ≥18 years from Jan 1, 2007 to Sep 30, 2017. Bleeding was defined as hospitalization or emergency room visit with a primary diagnosis of gastrointestinal (GI) bleeding, intracranial hemorrhage (ICH), or bleeding at other sites. Risk of overall and by type of bleeding was examined in concomitant users of DOAC and DR compared to patients using DOAC alone after adjusting for covariates of interest and applying propensity score (PS) trimming via Cox proportional hazards modeling. Results: Among concomitant users of DR and A (1,932), D (3,117), and R (2,395), crude incidence rates of bleeding per 1,000 person-years were 17.2, 37.8, 61.8, respectively versus 26.8, 31.3, and 44.9 in users of A (51,420), D (42,312), and R (57,300) alone. Incidence rates stratified by PS showed higher bleeding incidence in concomitant users of DR with D or R, but not with A. No increased bleeding risk was associated with use of DR and A vs A alone [Adjusted Hazard ratio (aHR): 0.69 (95% CI: 0.40, 1.17), p=0.16]. A modestly increased risk of GI bleeding but not overall bleeding was associated with combined use of DR and D vs D alone [aHR bleeding: 1.18 (95% CI: 0.89, 1.56), p=0.26; aHR GI bleeding: 1.40 (95% CI: 1.01, 1.93); p=0.04]. An increased risk of overall bleeding, driven by GI bleeding, was associated with combined use of DR and R vs R alone [aHR bleeding:1.31 (95% CI: 1.01, 1.69); p=0.04; aHR GI bleeding:1.39 (95% CI: 0.98, 1.95); p=0.06]. There was no increase in the risk of ICH associated with combined use of DR and any DOAC. Conclusions: Concomitant treatment with DR and A showed no increased risk of bleeding, but DR increased the risk of GI bleeding when given with D or R, and of overall bleeding only with R. Concomitant treatment with DR and any DOAC did not increase ICH risk.

Stroke prevention by Non-vitamin K Oral Anticoagulant (NOAC) agents in the absence of atrial fibrillation: meta-analysis of randomized control trials

Abstract Background Anticoagulation to prevent stroke is a mainstay of atrial fibrillation (AF) management. Patients with established cardiovascular disease (CVD) may have conditions that fulfil Virchow's triad for thrombogenesis even in sinus rhythm. Previous investigation into the benefit of warfarin compared to placebo or antiplatelet drug in sinus rhythm found a reduction in stroke rates, but with an increase in bleeding. The efficacy and safety of non-vitamin K oral anticoagulant (NOAC) agents has not been studied. Purpose To assess the safety and efficacy of NOAC agents in patients without AF. Methods An electronic database search for randomized controlled trials that evaluated a NOAC and control drug (placebo or antiplatelet) in non-AF patients with CVD was conducted up until 1 September 2019. The primary efficacy and safety outcomes were ischemic stroke and major bleeding, respectively. The net clinical benefit (NCB) was calculated as a weighted sum of rate differences of ischemic stroke and major bleeding. Groups were stratified according to intensity of anticoagulation (full vs. low dose NOAC). Results Twelve randomized controlled trials were identified with a total of 83,008 patients (50,617 on NOAC, 32391 on control drug; mean age 66±2.7 years). CVD included coronary artery disease (78.3%), hypertension (73.7%), diabetes mellitus (34.7%), peripheral arterial disease (30.3%), previous stroke (21.7%), renal disease (22.9%) and heart failure (18.4%). Over a mean follow-up of 17.3 months, 1347 (1.6%) ischemic strokes occurred. Use of NOAC was associated with 28% reduction in ischemic stroke (odds-ratio [OR] 0.72, 95% confidence-interval [CI] 0.60 to 0.87; 1.1 vs. 1.8 events per 100-person years), with numbers needed to treat of 145 patients to prevent one stroke. Major bleeding was increased nearly 2-fold (OR 1.83, 95% CI 1.46 to 2.29; 2.1 vs. 1.0 events per 100-person years). The NCB demonstrated overall harm with the use of NOAC agents in this patient population (NCB = −0.28, 95% CI: −0.79 to 0.23). Use of full dose NOAC was widely unsafe (NCB = −0.35, 95% CI: −1.25 to 0.54) and low dose NOAC approached null therapeutic safety advantage (NCB = −0.06, 95% CI: −0.47 to 0.35). Conclusion Patients with CVD are at increased of ischemic stroke in the absence of AF. The use of NOAC agents in this non-AF population reduces rate of ischemic stroke however overall risk of bleeding exceeds antithrombotic benefit. Low-dose NOACs demonstrate a neutral NCB suggesting a point of clinical equipoise and deserve further scrutiny. Ischemic stroke vs major bleeding Funding Acknowledgement Type of funding source: None

Anticoagulants' Safety and Effectiveness in General Practice: A Nationwide Prospective Cohort Study.

Most real-world studies on anticoagulants have been based on health insurance databases or performed in secondary care. The aim of this study was to compare safety and effectiveness between patients treated with vitamin K antagonists (VKAs) and patients treated with direct oral anticoagulants (DOACs) in a general practice setting. The CACAO study (Comparison of Accidents and their Circumstances with Oral Anticoagulants) is a multicenter prospective cohort study conducted among ambulatory patients taking an oral anticoagulant. Participants were patients from the study's cross-sectional phase receiving oral anticoagulants because of nonvalvular atrial fibrillation, for secondary prevention of venous thromboembolism, or both. They were followed as usual for 1 year by their general practitioners, who collected data on changes in therapy, thromboembolic events, bleeding, and deaths. All events were adjudicated by an independent committee. We used a propensity score and a Cox regression model to derive hazard ratios. Between April and December 2014, a total of 3,082 patients were included. At 1 year, 42 patients (1.7%) had experienced an arterial or venous event; 151 (6.1%) had experienced bleeding, including 47 (1.9%) who experienced major bleeding; and 105 (4.1%) had died. There was no significant difference between the VKA and DOAC groups regarding arterial or venous events, or major bleeding. The VKA group had a lower risk of overall bleeding (hazard ratio = 0.65; 95% CI, 0.43-0.98) but twice the risk of death (hazard ratio = 1.98; 95% CI, 1.15-3.42). VKAs and DOACs had fairly similar safety and effectiveness in general practice. The substantially higher incidence of deaths with VKAs is consistent with known data from health insurance databases and calls for further research to understand its cause.

Thromboembolic and bleeding risk of periprocedural bridging anticoagulation: A systematic review and meta-analysis.

The risk and benefit of periprocedural heparin bridging is not completely clarified. We aimed to assess the safety and efficacy of bridging anticoagulation prior to invasive procedures or surgery. Heparin bridging was associated with lower risks of thromboembolism and bleeding compared to non‐bridging. PubMed, Ovid and Elsevier, and Cochrane Library (2000‐2016) were searched for English‐language studies. Studies comparing interrupted anticoagulation with or without bridging and continuous oral anticoagulation in patients at moderate‐to‐high thromboembolic risk before invasive procedures were included. Primary outcomes were thromboembolic events and bleeding events. Mantel‐Haenszel method and random‐effects models were used to analyze the pooled risk ratio (RR) and 95% confidence interval (CI) for thromboembolic and bleeding risks. Eighteen studies (six randomized controlled trials and 12 cohort studies) were included (N = 23 364). There was no difference in thromboembolic risk between bridged and non‐bridged patients (RR: 1.26, 95% CI: 0.61‐2.58; RCTs: RR: 0.71, 95% CI: 0.23‐2.24; cohorts: RR: 1.45, 95% CI: 0.63‐3.37). However, bridging anticoagulation was associated with higher risk of overall bleeding (RR: 2.83, 95% CI: 2.00‐4.01; RCTs: RR: 2.24, 95% CI: 0.99‐5.09; cohorts: RR: 3.09, 95% CI: 2.07‐4.62) and major bleeding (RR: 3.00, 95% CI: 1.78‐5.06; RCTs: RR: 2.48, 95% CI: 1.29‐4.76; cohorts: RR: 3.22, 95% CI: 1.65‐6.32). Bridging anticoagulation was associated with increased bleeding risk compared to non‐bridging. Thromboembolism risk was similar between two strategies. Our results do not support routine use of bridging during anticoagulation interruption.

Intracranial haemorrhages vs. stent thromboses with direct oral anticoagulant plus single antiplatelet agent or triple antithrombotic therapy: a meta-analysis of randomized trials in atrial fibrillation and percutaneous coronary intervention/acute coronary syndrome patients.

To assess the efficacy-safety profile of dual antithrombotic therapy (DAT) including direct oral anticoagulant (DOAC) vs. triple antithrombotic therapy (TAT) in patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI). Randomized trials of AF patients with ACS/PCI, comparing DAT using DOACs against TAT, were selected. Overall, 11161 studies were screened, 458 trials assessed, and four included, comprising 10234 patients followed for a mean of 11 months. DAT compared to TAT resulted in significant reductions of trial-defined primary safety outcome [odds ratio (OR) 0.63, 95% confidence interval (CI) 0.50-0.79, number needed to treat (NNT) 17] and of thrombolysis in myocardial infarction (TIMI) major bleeding (OR 0.54, 95% CI 0.41-0.70, NNT 76) and in a numerical reduction of intracranial haemorrhage (OR 0.50, 95% CI 0.21-1.19, NNT 314), which became significant after exclusion of DOACs from TAT and vitamin K antagonist from DAT arms (OR 0.31, 95% CI 0.15-0.64). There were no significant differences in the risks of cardiovascular or any deaths or stroke, but with DAT, there was a numerical increase in myocardial infarctions (MIs) (OR 1.23, 95% CI 0.99-1.54, estimated NNT for an additional harmful outcome (NNTH) 151), which became significant in the ACS/PCI subgroup (OR 1.43, 95% CI 1.02-2.00), and a 60% significant increase in stent thrombosis risk (OR 1.60, 95% CI 1.02-2.52; NNTH 274). Dual antithrombotic therapy, compared to TAT, conferred a significantly reduced risk of overall bleeding but with a significant increase of stent thrombosis risk in the overall population and a significant 43% increase of MI in the ACS/PCI subgroup.

P763Home Monitoring is associated with fewer gastrointestinal bleeding events following ventricular assist device implantation

Abstract Introduction Patients (pts) treated with a continuous flow left ventricular assist device (LVAD) are at increased risk for both bleeding and thromboembolic events. Maintenance of oral anticoagulation (AC) in the therapeutic range is difficult to achieve. Hypothesis Increased frequency of international normalized ratio (INR) home monitoring (HM) decreases the incidence of gastrointestinal bleeding and thromboembolic events (stroke, pump thrombosis) compared to standard of care (SOC). Methods We analyzed the efficacy of outpatient AC monitoring in consecutive pts who underwent VAD implantation at our institution between 2008–2018. Time in therapeutic range (TTR) was defined as percent of time with INR 2.5–2.8. HM pts had biweekly INR measurements using the Coagucheck XS ROCHE, while SOC pts had INR measured every 1–3 weeks. Gastrointestinal bleeding (GIB) and thromboembolic events were assessed by retrospective blinded chart review. Logistic regression was used to model the impact of TTR on the risk of GIB and THROMB. Results There were 85 pts: 44 in HM and 40 in SC arm with similar characteristics. SOC patients were more likely to have ischemic cardiomyopathy (63% vs 30%, p=0.006) and an LVAD (60% vs 25%, p=0.002). The use of HM was associated with a 19.7% reduction in the risk of GIB (8.8% vs 28.5%, p=0.043) and a trend towards lower risk of THROMB (6.8% vs 14.9%, p=0.19). HM pts had significantly longer TTR (52±20% vs 39±22%, p=0.007). Each percentage increase in TTR was associated with a 5.2% decrease in the risk of GIB [Odds Ratio (OR) 0.95, 95% Confidence Interval (CI) 0.91–0.99, p=0.009] even after adjustment for aspirin use and monitoring duration (OR 0.95, 95% CI 0.91–0.99, p=0.020). There was a similar decrease in the risk of overall bleeding (OR 0.94, 95% CI 0.90–0.98, p=0.008). Conclusions Increased frequency of home INR monitoring achieved a higher TTR and was associated with a 20% reduction in risk of gastrointestinal bleeding.

Intranasal desmopressin reduces renal biopsy-related bleeding and serum sodium levels in patients with reduced renal function.

BackgroundThe use of desmopressin in preventing renal biopsy-related bleeding is not established and its effects on serum sodium levels are not well studied. The study aimed to compare the bleeding complication rates between the groups with and without desmopressin use prebiopsy and to observe the effect of desmopressin on postbiopsy serum sodium levels. MethodsIn this single-center, prospective and retrospective interventional study, from June 2018 onwards, patients with serum creatinine >132.6 μmol/L but not on dialysis and undergoing ultrasound-assisted needle-guided renal biopsy received 150 μg of desmopressin (D-amino D-arginine vasopressin (DDAVP)) (Group II). Data from patients from June 2017 to May 2018 were included in Group I in whom desmopressin was not used. Bleeding complications were monitored by clinical and ultrasound surveillance. Serum sodium levels were checked prior to and 24 h following desmopressin in Group II. ResultsA total of 194 patients were included in the study: 105 in Group I and 89 in Group II. Group II had lower overall minor bleeding complications and perinephric hematomas than Group I (15.7% versus 31.4%, 14% versus 27% and 7.8% versus 19% in Group II and Group I, respectively, with P < 0.05). Not using desmopressin and female sex were significant predictors for overall risk of bleeding on multivariate logistic regression. Serum sodium levels fell in 94% of patients in Group II. Lower prebiopsy serum sodium, higher estimated glomerular function rate and higher spot urine sodium values were associated with a greater decrease in serum sodium after desmopressin.ConclusionIntranasal desmopressin reduces bleeding complications during renal biopsies performed in patients with reduced renal function not requiring dialysis, albeit with a risk of developing hyponatremia.

Risk of Bleeding with Ibrutinib in Patients with B-Cell Malignancies: An Updated Meta-Analysis of Phase III Randomized Controlled Trials

Introduction: Ibrutinib is an oral Bruton's tyrosine kinase (BTK) inhibitor which has transformed the management of several B-cell malignancies. Ibrutinib has been associated with an increased incidence of bleeding in retrospective studies. This phenomenon has been explained by potential effects of ibrutinib on different aspects of platelet function, including adhesion and aggregation, mainly through modification of BTK signaling pathways in platelets. A previous meta-analysis (Caron et al.) found a significant increase in overall bleeding in ibrutinib recipients. We conducted an updated systematic review and meta-analysis of all phase III randomized controlled trials (RCT) available till date to determine the relative risk of overall bleeding associated with ibrutinib use, relative risk of major hemorrhage, and to evaluate if the risk estimate has changed with emergence of new data since prior reports.Methods: We performed a systematic search of Embase, PubMed, Web of Science, Scopus, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and Clinical Trials.gov with appropriate keywords through 07/10/18, to find all RCTs comparing ibrutinib with other agents or placebo in patients with B-cell malignancies and also reporting bleeding as a treatment-emergent adverse event. The search strategy, study selection, data extraction, and analysis were performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines. We pooled the point estimates using random effects model of the generic inverse-variance method described by Der Simonian and Laird. Statistical analyses were performed using the Stata/SE 15.1 (StataCorp LP, College Station, TX, USA).Results: A total of 6 phase III RCTs randomizing 1811 patients (pt; 935 on ibrutinib arms and 876 in the control arms) were included in the final analysis. Four trials were conducted in pts with CLL, one in pts with Waldenstrom macroglobulinemia and the other one in pts with mantle cell lymphoma. Characteristics of these trials are shown in Table 1. In 4 RCTs ibrutinib was compared with an active agent (i.e., ofatumumab, chlorambucil, temsirolimus, and rituximab) and in the other two trials, it was compared with placebo. Ibrutinib was administered as a 1st-line therapy in the RESONATE-2 trial and both as 1st line and in refractory cases in the iNNOVATE trial. The median duration of treatment across studies with ibrutinib was 17.7 months (range 9.4-38.7 months). Major hemorrhage was usually defined as grade 3-5 bleeding or central nervous system bleeding of any grade across trials. The pooled risk ratio (RR) for total number of bleeding events was 2.43 [95%CI: 1.47-4.00, p<0.001, I2=82.5%, figure 1A] in patients on ibrutinib across all B-cell malignancies, as compared to their counterparts in the control arms. The pooled RR for incidence of major hemorrhage in the ibrutinib arm was 1.71 [95%CI: 0.99-2.95, p=0.056, I2=0.0%, figure 1B], showing trend towards statistical significance as compared to control. In subgroup analysis of trials (n=4) in pts with CLL only, ibrutinib was again associated with a significantly increased risk of overall bleeding [pooled RR 3.23, 95%CI: 1.72-6.06, p<0.001, I2=72.7%, figure 2A], although the relative increase in risk was not significant [pooled RR 1.74, 95%CI: 0.83-3.67, p=0.142, I2=0.0%, figure 2B] in the patients on ibrutinib when number of major hemorrhages were compared in both groups. No publication bias was observed across all the studies included in final analysis.Conclusion: In this meta-analysis, ibrutinib was associated with a significantly increased risk of overall bleeding in patients with B-cell malignancies, and incidence of major hemorrhages in ibrutinib arm showed trend towards statistical significance. Knowledge about increased risk of this adverse event should help clinicians to contribute to alleviation of overall morbidity and mortality in patients. DisclosuresMaiti:Celgene Corporation: Other: Research funding to the institution.

Incidence of major hemorrhage after aggressive image-guided liver mass biopsy in the era of individualized medicine.

To analyze a large volume of image-guided liver mass biopsies to assess for an increased incidence of major hemorrhage after aggressive liver mass sampling, and to determine if coaxial technique reduces major hemorrhage rate. Patients who underwent image-guided liver mass biopsy over a 15-year period (December 7, 2001-September 22, 2016) were retrospectively identified. An aggressive biopsy was defined as a biopsy event in which ≥ 4 core needle passes were performed. Association of major hemorrhage after aggressive liver mass biopsy and other potential risk factors of interest were assessed using logistic regression analysis. For the subset of aggressive biopsies, Fisher's exact test was used to compare the incidence of major hemorrhage using coaxial versus noncoaxial techniques. Aggressive biopsies constituted 11.6% of biopsy events (N =579/5011). The incidence of major hemorrhage with <4 passes was 0.4% (N =18/4432) and with ≥4 passes 1.2% (N =6/579). In univariable models, aggressive biopsy was significantly associated with major hemorrhage (OR 3.0, 95% CI 1.16-6.92, p =0.025). After adjusting for gender and platelet count, the association was not significant at the p =0.05 level (OR 2.58, 95% CI 0.927-6.24, p =0.067). The rate of major hemorrhage in the coaxial biopsy technique group was 1.4% (N =3/209) compared to 1.1% (N =4/370) in the noncoaxial biopsy technique group, which was not a significant difference (p =0.707). Although aggressive image-guided liver mass biopsies had an increased incidence of major hemorrhage, the overall risk of bleeding remained low. The benefit of such biopsies will almost certainly outweigh the risk in most patients.

Eltrombopag versus romiplostim in treatment of children with persistent or chronic immune thrombocytopenia: a systematic review incorporating an indirect-comparison meta-analysis

In absence of direct comparison, we conducted an indirect-comparison meta-analysis to evaluate the efficacy and safety of thrombopoietin-receptor agonists(TPO-RAs) in treatment of pediatric persistent or chronic immune thrombocytopenia(ITP). PubMed, Embase, Cochrane Library, Clinical Trials.gov, China National Knowledge Infrastructure, and Chinese Biomedical Literature Database were searched from their earliest records to May 2017. Randomized controlled trials comparing the TPO-RAs with placebo in pediatric ITP were included. Outcomes included overall response rate(primary), durable response, overall or clinically significant bleeding, the proportion of patients receiving rescue medication, and safety. Five randomized placebo-controlled studies(N = 261) were analyzed. The overall response[Risk Ratio(RR) 0.57, 95% confidence interval(CI) 0.21–1.56], the incidence of adverse events (RR 0.96, 95%CI 0.66–1.39), durable response(RR 2.48, 95%CI 0.31–19.97), and the proportion of patients receiving rescue treatment(RR 0.73, 95%CI 0.20–2.73) were similar between eltrombopag and romiplostim group. Nevertheless, eltrombopag might have lower risk of overall bleeding(RR 0.43, 95%CI 0.23–0.80) and clinically significant bleeding(RR 0.33, 95%CI 0.12–0.89) than romiplostim. This meta-analysis suggests that eltrombopag might be similar to romiplostim in efficacy and safety, but seems to reduce the risk of bleeding compared to romiplostim. Furthermore, cost of the treatment, comorbidity of patients and drug compliance should also be considered in clinical decision making.

Administration of Ticagrelor and Double-Dose Clopidogrel Based on Platelet Reactivity Determined by VerifyNow-P2Y12 for Chinese Subjects After Elective PCI.

Previous studies have identified high on treatment platelet reactivity (HTPR) as a potent factor predicting ischemic events for patients with coronary heart disease. We assessed the efficacy and safety of ticagrelor (90 mg twice-daily) and double-dose of clopidogrel (150 mg once-daily) among Chinese patients for elective percutaneous coronary intervention. We enrolled 40 patients with HTPR from among 317 patients with non-ST-segment elevation acute coronary syndromes after a successful elective percutaneous coronary intervention (PCI). Platelet reactivity was measured by VerifyNow P2Y12 assay. Platelet reactivity was significantly lower for both groups when compared with baseline platelet reactivity after medication adjustment (all P < 0.001). The mean platelet reactivity units (PRU) was significantly lower for the ticagrelor group compared with that of the clopidogrel group over time (all P < 0.001). The differences in the rate of sustained HTPR at different time points between the two groups were significant (2 hours: 0% versus 60%; 8 hours: 5.6% versus 50%; 24 hours: 5.9% versus 43.8%, all P < 0.05). Genetic variation of CYP2C19*2 had no impact on PRU means or rate of HTPR in the ticagrelor group (P > 0.05). During the 30-day follow-up, no MACE occurred in any patient, and the overall risk of bleeding showed no difference between the two groups (35% versus 21%, P = 0.48). Our results suggest that ticagrelor may achieve a more rapid and greater platelet inhibition than double-dose clopidogrel. Further studies are still needed to assess the differences in efficacy and safety between ticagrelor and double-dose clopidogrel administration for Chinese patients post elective PCI.