Reduction In Bleeding Events Research Articles

Duration of dual antiplatelet therapy and outcome in patients with acute coronary syndrome undergoing percutaneous revascularization: A meta-analysis of 11 randomized trials

BackgroundAcute coronary syndromes (ACS) represent a context of higher thrombotic risk, where larger advantages have been achieved by the administration of dual antiplatelet therapy (DAPT). However, the indication of 1 year DAPT after coronary angioplasty for ACS has been supported by an outdated randomized trial (PCI-CURE). In addition, the initial fear of late thrombotic events emerged with first generation drug-eluting stents (DES), that suggested the need of a prolonged DAPT prescription, has been completely overcome by the recent technological evolution of DES, that have shown faster re-endothelization and lower rates of late thrombotic complications. By keeping in mind the balance between thrombotic and bleeding complications, and due to the paucity of dedicated randomized trials, the identification of the optimal duration of DAPT after ACS is still matter of debate, and is therefore the aim of the present meta-analysis. MethodsLiterature and main scientific session abstracts were searched. The primary efficacy endpoint was mortality, primary safety endpoint was the occurrence of major bleedings. A pre-specified analysis was conducted according to the DAPT strategy allocation (<12 vs standard 12 months duration and 6–12 months vs extended DAPT). ResultsWe included 3 RCTs and subanalyses from 8 RCTs, with a total of 17,941 patients. No difference in mortality was observed between shorter vs longer DAPT (OR[95%CI] = 1.11[0.90,1.36], p = 0.33; phet = 0.76). A shorter DAPT duration significantly reduced the rate of major bleeding events (1.5%, vs 1.9%, OR [95%CI] = 0.75 [0.60, 0.94], p = 0.01; phet = 0.43). The reduction in bleeding events was more significant in trials evaluating extended DAPT duration (OR[95%CI] = 0.62[0.45, 0.85], p = 0.003; phet = 0.49). No difference in cardiovascular mortality, myocardial infarction and stent thrombosis was observed with shorter vs standard 12-moth DAPT, whereas a more extended treatment (beyond 1 year), was associated with a significant reduction in recurrent ischemic events. Similar results were observed at a sensitivity analysis conducted according to the type of stent, time to randomization or DAPT duration. ConclusionsBased on the current meta-analysis including 17,941 ACS patients undergoing PCI, a short duration of DAPT may be safely considered, with similar rates of recurrent thrombotic complications as compared to the standard 12 months, and similar mortality. A more extended DAPT administration (beyond 1 year) provides benefits in ischemic events, but with an excess in haemorragic complications, with overall neutral effects on mortality.

PD01 IPC For Prevention Of VTE: An Economic Analysis

Introduction:Total hip and knee arthroplasty (THKA) patients are at risk of venous thromboembolism (VTE). Guidelines recommend 10–35 days of pharmacoprophylaxis, but this may induce bleeding resulting in increased healthcare costs. This study assessed whether using intermittent pneumatic compression (IPC) for VTE prophylaxis is associated with reduced healthcare costs compared to anticoagulants.Methods:Studies related to VTE and prophylaxis in THKA were identified by a structured search of the PubMed database. VTE incidence and cost data were Australia specific or, if not available, taken from other developed healthcare systems. A Markov model was used to estimate the incidence of deep vein thrombosis (DVT), pulmonary embolism (PE), death, post-thrombotic syndrome, as well as minor and major bleeding and heparin-induced-thrombocytopenia, to assess the budget impact of different VTE prophylaxis strategies. The time horizon was one year, low-molecular-weight-heparin (LMWH) was used as the reference intervention, and effectiveness data were obtained from meta-analyses.Results:A total of 102,459 THKA were performed in Australia in 2015. The twelve-day incidence of DVT and PE using LMWH prophylaxis were 4.48 percent and 0.25 percent, respectively, with minor and major bleeding occurred in 9.9 percent (within twelve days) and 1.9 percent (within 10 days) of the patients, respectively. The incidence of VTE was not different between LMWH and IPC after THKA. The model estimated that the total cost of post-operative care for THKA was AUD 101.7 million (USD 77 million) in 2015. A one percent-point change from LMWH to IPC prophylaxis (n=1025 patients) would reduce the total healthcare costs by AUD 317,361 (USD 240,274) per year (or AUD 310 (USD 235) per patient), primarily through reduced bleeding events (-72 minor and -3 major bleeds). Sensitivity analysis including 500 simulations demonstrated a likelihood of 100 percent for IPC to reduce both costs and bleeding events compared to LMWH. Similarly, a one percent-point change from dabigatran and rivaroxaban to IPC also resulted in total healthcare savings of AUD 320,580 (USD 242,711) and AUD 702,584 (USD 531,926) per year, respectively, with two-thirds and ninety-nine percent of the simulations favored IPC over dabigatran for bleeding and cost savings, respectively.Conclusions:Using IPC for VTE prophylaxis after THKA has the potential to substantially reduce total healthcare costs compared to anticoagulants, primarily through reduced bleeding events. IPC is suitable for all patients, but may be particularly cost-effective in the immediate postoperative period or in patients at high-risk of bleeding.

Clinical and Economic Impact of a Multisciplinary Intervention to Reduce Bleeding Risk in Patients With Acute Coronary Syndrome

Introduction and objectivesTo evaluate the clinical and economic impact of a multidisciplinary program to reduce bleeding events in patients with acute coronary syndrome through optimization of antithrombotic therapy. MethodsWe designed a preintervention (PRE) and postintervention (POST) quasi-experimental study using a retrospective analysis of 2 cohorts. The first cohort was analyzed to detect correctable measures contributing to bleeding (PRE). Afterward, a quality improvement intervention with a bundle of recommendations was implemented. Finally, a second cohort of patients was evaluated to investigate the impact of the measures on bleeding reduction (POST). The impact on health outcomes was evaluated through comparison of the percentage of in-hospital bleeding events and 30-day readmissions between the 2 cohorts. The economic analysis took into account the costs associated with the implementation of the program and the cost-savings associated with the prevention of bleeding events and 30-day readmissions. ResultsA total of 677 patients were included (377 in PRE and 300 in POST). The total bleeding rate was reduced after the implementation of the bundled intervention by 29.2% (31.6% in POST vs 22.3% in PRE; OR, 0.62; 95%CI, 0.44-0.88) while 30-day readmission rates were 7.7% in PRE and 5% in POST (P=.20). The estimated avoided cost was €95 113.6 per year, meaning that €10.1 would be obtained in return for each euro invested during the first year and €36.3 during the following years. ConclusionsThis multidisciplinary program has proven to be effective in reducing bleeding events and is economically attractive.

Edoxaban for stroke prevention in atrial fibrillation and treatment of venous thromboembolism: an expert position paper

Edoxaban is the most recent available representative of the Non-VitaminK antagonist oral anticoagulants (NOAC). The approval was based on the largest phaseIII trials of NOACs for stroke prevention in patients with non-valvular atrial fibrillation (AF, ENGAGE-AF), and for the treatment of venous thromboembolism (VTE, HOKUSAI-VTE). In both trials, edoxaban was associated with similar efficacy and asignificant reduction in bleeding events with respect to the pre-defined primary safety endpoints, as compared to warfarin.Additionally, the once daily dosing of edoxaban, the clinically investigated strategy for dose-reduction based on clearly defined criteria and the favorable pharmacokinetic profile might further support the clinical applicability of the substance.In the light of recent data, this expert consensus document aims to summarize the latest clinical trial results while providing aconcise overview of current guideline recommendations on the management of patients with non-valvular AF and VTE.

Análisis de los resultados económicos y en salud de un programa dirigido a la reducción de hemorragia en pacientes con síndrome coronario agudo

Introduction and objectivesTo evaluate the clinical and economic impact of a multidisciplinary program to reduce bleeding events in patients with acute coronary syndrome through optimization of antithrombotic therapy. MethodsWe designed a preintervention (PRE) and postintervention (POST) quasi-experimental study using a retrospective analysis of 2 cohorts. The first cohort was analyzed to detect correctable measures contributing to bleeding (PRE). Afterward, a quality improvement intervention with a bundle of recommendations was implemented. Finally, a second cohort of patients was evaluated to investigate the impact of the measures on bleeding reduction (POST). The impact on health outcomes was evaluated through comparison of the percentage of in-hospital bleeding events and 30-day readmissions between the 2 cohorts. The economic analysis took into account the costs associated with the implementation of the program and the cost-savings associated with the prevention of bleeding events and 30-day readmissions. ResultsA total of 677 patients were included (377 in PRE and 300 in POST). The total bleeding rate was reduced after the implementation of the bundled intervention by 29.2% (31.6% in POST vs 22.3% in PRE; OR = 0.62; 95%CI, 0.44-0.88) while 30-day readmission rates were 7.7% in PRE and 5% in POST (P = .20). The estimated avoided cost was 95 113.6€ per year, meaning that 10.1€ would be obtained in return for each euro invested during the first year and 36.3€ during the following years. ConclusionsThis multidisciplinary program has proven to be effective in reducing bleeding events and is economically attractive.Full English text available from:www.revespcardiol.org/en

Predictors of clinically significant bleeding events in bivalirudin-treated Chinese patients with acute myocardial infarction undergoing percutaneous coronary intervention

Objective: This study was designed to further clarify the independent predictors of clinically significant bleeding events in bivalirudin-treated patients with acute myocardial infarction(AMI) undergoing percutaneous coronary intervention (PCI). Methods: A total of 3 023 AMI patients from 88 centers of China who underwent PCI and received periprocedural bivalirudin treatment between August 2012 and December 2015 were involved in this study.The primary outcome was clinically significant bleeding events defined as the Bleeding Academic Research Consortium(BARC) grades 2-5, with 30 days after PCI.A multivariate Logistic regression model was performed to identify the independent predictors of the primary outcome. Results: Bleeding events occurred in 88(2.9%) patients during the 30-day follow up, with clinically significant bleeding (BARC types 2-5) in 22(0.7%) and BARC types 3-5 in 7(0.2%). Multivariate regression analysis revealed radial access (OR: 0.196, 95%CI: 0.074-0.517, P=0.001) as the independent protector of the significant bleeding events, anemia (OR: 2.956, 95%CI: 1.024-8.528, P=0.045) and eGFR<30 ml/min (OR: 7.860, 95%CI: 1.515- 40.776, P=0.014) as independent risk factors. Conclusions: The rate of clinically significant bleeding complications in Chinese AMI patients undergoing PCI with concomitant use of bivalirudin is low in real-world clinical practice.Radial access is independent protective factor that reduces bleeding events, whereas anemia and eGFR <30 ml/min are independent risk factors that increase bleeding risk.

Eltrombopag versus placebo for low-risk myelodysplastic syndromes with thrombocytopenia (EQoL-MDS): phase 1 results of a single-blind, randomised, controlled, phase 2 superiority trial

In myelodysplastic syndromes, thrombocytopenia is associated with mortality, but treatments in this setting are scarce. We tested whether eltrombopag, a thrombopoietin receptor agonist, might be effective in improving thrombocytopenia in lower-risk myelodysplastic syndromes and severe thrombocytopenia. EQoL-MDS was a single-blind, randomised, controlled, phase 2 superiority trial of adult patients with low-risk or International Prognostic Scoring System intermediate-1-risk myelodysplastic syndromes and severe thrombocytopenia. Patients with a stable platelet count of lower than 30 × 109 platelets per L, aged at least 18 years, with refractoriness, ineligibility to receive treatment with alternative medications, or relapse while receiving treatment with alternative medications were included in this trial. Patients were randomly assigned (2:1) to receive eltrombopag (50 mg to 300 mg) or placebo for at least 24 weeks and until disease progression and were masked to treatment allocation. Here, we report the results in the intention-to-treat population of the first phase of the trial, for which the primary endpoints were the proportion of patients achieving a platelet response within 24 weeks and safety. The interim analysis presented here was protocol-specified and used a two-sided significance level of 0·001 and a p value at or below this limit for both primary endpoints to indicate the need for early trial termination. Duration of platelet transfusion independence, duration of response, overall survival, leukaemia-free survival, and pharmacokinetics will be reported at the end of the phase 2 portion of the trial. This trial is registered with EudraCT, number 2010-022890-33. Between June 13, 2011, and June 17, 2016, we enrolled 90 participants for the first phase of the trial. The median follow-up time to assess platelet responses was 11 weeks (IQR 4-24). Platelet responses occurred in 28 (47%) of 59 patients in the eltrombopag group versus one (3%) of 31 patients in the placebo group (odds ratio 27·1 [95% CI 3·5-211·9], p=0·0017). During the follow-up, 21 patients had at least one severe bleeding event (WHO bleeding score ≥2). There were a higher number of bleeders in the placebo (13 [42%] of 31 patients) than in the eltrombopag arm (eight [14%] of 59 patients; p=0·0025). 52 grade 3-4 adverse events occurred in 27 (46%) of 59 patients in the eltrombopag group versus nine events in five (16%) of 31 patients in the placebo group (χ2=7·8, p=0·0053, stopping rule not reached). The outcome acute myeloid leukaemia evolution or disease progression occurred in seven (12%) of 59 patients in the eltrombopag group versus five (16%) of 31 patients in the placebo group (χ2=0·06, p=0·81). Eltrombopag is well-tolerated in patients with lower-risk myelodysplastic syndromes and severe thrombocytopenia and is clinically effective in raising platelet counts and reducing bleeding events. The assessment of long-term safety and efficacy of eltrombopag and its effect on survival (phase 2 part of study) is still ongoing. Associazione QOL-ONE.

Romiplostim in Thrombocytopenic Patients with Low- or Int-1- Risk MDS Results in Reduced Bleeding without Impacting Leukemic Progression: Final Follow-up Results from a Randomized, Double-Blind, Placebo-Controlled Study

Romiplostim in Thrombocytopenic Patients with Low- or Int-1- Risk MDS Results in Reduced Bleeding without Impacting Leukemic Progression: Final Follow-up Results from a Randomized, Double-Blind, Placebo-Controlled Study

Alternative agents to prophylactic platelet transfusion for preventing bleeding in people with thrombocytopenia due to chronic bone marrow failure: a meta-analysis and systematic review.

Alternative agents to prophylactic platelet transfusion for preventing bleeding in people with thrombocytopenia due to chronic bone marrow failure: a meta-analysis and systematic review.

TCT-343 Implementation of an Electronic Medical Record Based Bleeding Risk Calculator to Reduce Bleeding Events after PCI

Bleeding events are the most common complication of percutaneous coronary interventions (PCI). A severe bleeding event can outweigh the benefits of a PCI, contributing to increased morbidity, mortality and costs. We sought to develop an electronic medical record (EMR) based system to assess bleeding

Impact of a Guideline for the Management of Antimicrobial/Warfarin Interactions in the Inpatient Setting and Across Transition of Care

Drug-drug interactions (DDIs) with warfarin and antimicrobial agents are a common cause of international normalized ratio (INR) instability, which can affect the risk for bleeding and thrombotic events. The purpose of this study was to assess the impact of a comprehensive guideline for the management of warfarin-antimicrobial DDIs across transitions of care. The guideline emphasizes improving identification of significant antimicrobial-warfarin DDIs during hospitalization, empirical warfarin dose modification based on DDI and baseline INR, patient education, documentation of the DDI, communication with outpatient providers regarding the DDI and anticipated antimicrobial stop date, and warfarin dose adjustment on discontinuation of antimicrobial. This retrospective, single-center, quasiexperimental, pre-post study compared end points 3 months before and after guideline implementation. The primary outcome was time within therapeutic range (TTR). The study included 78 preguideline and 31 postguideline patients; baseline characteristics were similar between groups. Implementation of the guideline resulted in greater in-hospital TTR (72% vs 50%, P = 0.04) and improved TTR across transition of care (70% vs 46%, P = 0.01). Documentation of DDI in the pharmacy anticoagulation discharge summary significantly improved in the postguideline group (40% vs 14%, P = 0.02) and numerically improved within the daily pharmacy progress notes (94% vs 82%, P = 0.13). The implementation of the guideline was associated with a nonsignificant, numerical reduction in bleeding events compared with the preguideline group (0 vs 4 events, P = 0.11). This single-center approach to optimize the comprehensive management of significant antimicrobial-warfarin DDIs resulted in improved communication with outpatient providers and improved INR TTR.

Left atrial appendage occlusion for stroke prevention in atrial fibrillation: multicentre experience with the AMPLATZER Cardiac Plug.

To investigate the safety, feasibility, and efficacy of left atrial appendage occlusion (LAAO) with the AMPLATZER Cardiac Plug (ACP) for stroke prevention in patients with atrial fibrillation (AF). Data from consecutive patients treated in 22 centres were collected. A total of 1,047 patients were included in the study. Procedural success was 97.3%. There were 52 (4.97%) periprocedural major adverse events. Follow-up was complete in 1,001/1,019 (98.2%) of successfully implanted patients (average 13 months, total 1,349 patient-years). One-year all-cause mortality was 4.2%. No death at follow-up was reported as device-related. There were nine strokes (0.9%) and nine transient ischaemic attacks (0.9%) during follow-up. The annual rate of systemic thromboembolism was 2.3% (31/1,349 patient-years), which is a 59% risk reduction. There were 15 major bleedings (1.5%) during follow-up. The annual rate of major bleeding was 2.1% (28/1,349 patient-years), which is a 61% risk reduction. Patients with single LAAO on aspirin monotherapy or no therapy and longer follow-up had fewer cerebral and fewer bleeding events. In this multicentre study, LAAO with the ACP showed high procedural success and a favourable outcome for the prevention of AF-related thromboembolism. Modification in antithrombotic therapy after LAAO may result in reduction of bleeding events.

Liberal Vs. Restrictive Transfusion Thresholds in Leukemia Patients: A Feasibility Pilot Study

Transfusion of red blood cells (RBCs) is vitally important for the care of patients (pts) undergoing myelosuppressive therapy for acute leukemia (AL). At diagnosis and before bone marrow recovery, RBCs are given liberally with hemoglobin (Hb) transfusion triggers of 8-9 g/dL or higher, often with two RBC units given at a time. Research in a variety of non-oncologic settings suggests that lower Hb triggers (7-8 g/dL) do not increase mortality whereas higher Hb triggers (9 g/dL) may increase mortality. For pts with hematologic malignancies, the ideal Hb threshold is unknown. Also, there is literature to suggest that higher Hb values force platelets to the periphery of capillaries and reduce bleeding events. A study of red cell triggers in pts with thrombocytopenia (as in AL) is important as we may not be able to rely on trigger data from others in this setting. This feasibility study was designed to determine whether a randomized trial of Hb triggers could be performed and what challenges may be encountered with this select population.In this prospective randomized study, we enrolled adult pts with AL (myeloid and lymphoid) undergoing intensive induction therapy to evaluate both patient and physician tolerance for a transfusion threshold of 7g/dL (LOW) compared to the standard threshold of 8g/dL (HIGH), as well as operationalize transfusion to a single unit per episode. Pts were randomized with a 2:1 ratio of LOW threshold to HIGH threshold. Pts were ineligible if there was clinical concern for acute coronary syndrome or active blood loss. Pts were monitored from the study enrollment date through the next marrow evaluation after completion of induction therapy. Vital status at Day 60, accrual rate, and safety endpoints (mortality, length of stay, infection, fatigue scores, renal, respiratory, thrombotic, bleeding events) were monitored. Total transfusions, length of inpatient stay, and percentage of pts who crossed over to HIGH threshold for symptomatic reasons were also monitored.Between April 15, 2014 and July 23, 2015, 162 acute leukemia pts would have been eligible for this trial. Of the eligible pts, 112 (69%) were approached and 90 (of planned 90) have enrolled to date. Twenty-two pts (19.6%) of those offered the trial declined. Seventy-four pts are currently evaluable for response (13 pts have not been on-study long enough to evaluate and 3 pts are not eligible for data analysis): 51 pts in LOW arm and 23 in HIGH arm. Interim data is shown in Table 1. In the LOW arm, three pts withdrew consent due to self-reported fatigue and one patient was removed by physician due to clinical scenario. Seventeen pts (33%) in the LOW arm and six pts (26%) in the HIGH arm were transfused outside their hemoglobin trigger without meeting criteria to discontinue the study. No deaths were attributable to Hb thresholds in this study. Significant bleeding events (Grade 3 or 4 by CTCAE 4.0) were comparable with 4 in LOW arm and 3 in HIGH arm. More minor bleeding events (Grade 1 or 2 by CTCAE 4.0) were higher in LOW (24 events) than in HIGH arm (15 events).Acute leukemia and its therapies carry a significant mortality risk and it is not clear how transfusion thresholds and number of PRBC units transfused impact this mortality. Furthermore, blood is an expensive and scarce resource. Without a clear benefit of higher Hb thresholds, the added risks and costs of transfusion may not be justified. This pilot study shows that both pts and leukemia physicians will tolerate randomization between Hb thresholds and there is not a signal for harm in either Hb threshold at present. Pts in the LOW arm receive fewer transfusions and do not experience higher fatigue scores nor increased significant bleeding events. Length of hospitalization was similar in both arms. This safety data will serve as a platform for a larger mortality study in leukemia and possibly additional studies in other oncologic diseases.Table 1LOWHIGHP valuePatients (n)51 (69%)23 (31%)Gender Male23 (45%)11 (48%)Median Age (Years)58630.35AML44 (86%)18 (78%)ALL5 (10%)5 (22%)APL2 (4%)0Patients Alive at Day 6046 (90%)21 (91%)Red Cell Transfusions in Units (Median)8 (IQR: 5)10 (IQR: 4)0.008*Platelet Transfusions in Episodes (Median)9 (IQR: 6.5)9 (IQR: 5)0.86Length of Stay (Median)35 (IQR: 10)36 (IQR: 15)0.72Fatigue Scale Score (Median)4.33 (IQR: 1)4.54 (IQR: 1.25)0.40AML: acute myeloid leukemia; ALL: acute lymphoid leukemia; APL: acute promyelocytic leukemia DisclosuresNo relevant conflicts of interest to declare.

Cost-Effectiveness of Romiplostim As First-Line Primary Immune Thrombocytopenia (Itp) Treatment in Adult Splenectomised Patients Who are Refractory to Other Treatments and As Second-Line Itp Treatment in Adult Non-Splenectomised Patients Where Surgery is Contraindicated in Colombia

To conduct a cost-effectiveness analysis of romiplostim as first-line ITP treatment in adult splenectomised patients who are refractory to other treatments and as second-line treatment in adult non-splenectomised patients for whom surgery is contra-indicated vs. eltrombopag. A Markov model with embedded decision tree containing three health status (platelets≥50×109/L; platelets<50×109/L; and dead) was developed from a Colombian Health Ministry perspective and evaluated at 4-week cycles over a lifetime horizon. Efficacy was characterized by initial response; mean time to response, and duration of response and was estimated from literature review. Used resources and treatment patterns were obtained by a modified Delphi panel from a group of four hematologist. Costs include drug administration, visits, laboratory tests, rescue therapy, intracranial, GI and gynecological bleeding. Social Security costs (ISS+30) are used for procedures, visits and laboratory tests; and SISMED-2014 prices for drugs. Clinical benefits and costs are discounted 5% per annum. Total expected treatment cost for romiplostim arm was $1,276,302,002 (romiplostim cost $408,991,91; subsequent treatment lines $4,612,365; rescue therapy (IVIg and IV steroids) $859,929,341; and bleedings $2,768,379) vs. $1,315,173,138 for eltrombopag arm (eltrombopag cost $191,795,316; subsequent treatment lines $5,836,389; rescue therapy $1,113,981,314; and bleedings $3,560,119). Use of romiplostim, compared with eltrombopag, increased 4.46 years response duration, prevented 4.5 bleeding episodes and 1.5 admissions over a lifetime horizon. Romiplostim proves to be the dominant approach compared with eltrombopag. Use of romiplostim in the ITP treatment pathway, compared with eltrombopag, improves clinical outcomes, by increasing and maintaining platelet count, reducing bleeding events and rescue therapy need. These benefits generate cost savings and positioning romiplostim as a dominant approach.

Early stent thrombosis with bivalirudin in patients undergoing percutaneous coronary intervention. A meta-analysis of randomised clinical trials.

Although bivalirudin has been shown to reduce bleeding events in patients undergoing percutaneous coronary intervention, residual concerns remain about a possible higher risk of early (within 30 days) stent thrombosis (ST). Therefore, we performed a meta-analysis of randomised trials reporting ST events with bivalirudin compared to other antithrombotic therapies (heparins ± glycoprotein IIb/IIIa inhibitors). A systematic literature search of electronic resources was performed through May, 2014. The primary endpoint was definite early ST, according to Academic Research Consortium criteria. Secondary endpoints included: all-cause death, myocardial infarction and major bleeding. A total of 11 trials, including 16,415 patients, were accrued. Compared to other regimens, bivalirudin significantly increased the risk of early ST (odds ratio [OR]=1.80; 95 % confidence interval [CI], 1.28-2.52; p=0.0007) and reduced the risk of major bleeding (OR [95 %CI]=0.64 [0.51-0.82], p=0.0003), with a comparable risk of mortality or myocardial infarction. The higher risk of early ST was mainly attributable to acute (OR [95 % CI] =4.33 [2.33-8.05], p < 0.001) than subacute (OR [95 % CI] =0.89 [0.53-1.50], p =0.67) ST events (p for interaction < 0.001). Non-fatal myocardial infarction was the most common presentation (83 %) of early ST events, while death occurred infrequently (about 5 %). In conclusion, in patients undergoing PCI, bivalirudin compared to heparins is associated with a higher risk of early ST, which is mainly related to more frequent acute events. Further studies are required to evaluate alternative strategies to mitigate this risk, without hampering the benefits derived from the reduction in bleeding events with bivalirudin.

Institutional Switch from Transfemoral to Transradial Vascular Access for Percutaneous Coronary Intervention was Associated with a Reduction in Bleeding Events: A Singlecenter Experience of >10,000 Consecutive Cases.

Transradial (TR) access for percutaneous coronary intervention (PCI) reduces bleeding compared with transfemoral (TF) access, and may reduce mortality in specific patient subsets. However, switching from TF to TR access is associated with a learning curve and it is unclear whether benefits observed in randomized trials translate into practice. We sought to characterize the trends in bleeding and mortality rates at our institution, as we changed from being a TF to predominantly TR center over a 5-year period. 10,213 consecutive patients presenting for PCI were included (mean age 65.0 ± 11.6 years, 76.1% male, 48.0% PCI for acute coronary syndrome) over 5 years at a single center with PCI volume >2,000 cases per annum. Patients were stratified by initial arterial access site (TR or TF) and outcome measures included temporal trends in TR procedural failure, 30-day bleeding complications and all-cause 1-year mortality. TR procedural failure fell to a consistently low rate within 1 year (11.8% in 2008 to 2.9% in 2009, P < 0.001). As TR volume increased, the annual 30-day bleeding rate fell (1.64% in 2008 to 0.68% in 2012, P = 0.006). TR access predicted reduced 30-day bleeding (OR 0.17 [95%CI 0.07-0.38], P < 0.001), but was not a predictor of 1-year survival (HR 0.78 [95%CI 0.58-1.05], P = 0.10). Successful transition from TF to TR PCI at our institution was rapid and associated with a reduction in 30-day bleeding. These data should encourage other centers considering the adoption of TR access.

Surgical treatment of denture-induced fibrous hyperplasia with plasma rich in growth factors.

Denture-induced fibrous hyperplasia is a fibrous connective tissue lesion that commonly occurs in oral mucosa in patients showing important alveolar ridge atrophy. In this study, we propose Plasma Rich in Growth Factors (PRGF) to overcome constrains of traditional surgical treatment. Herein, we demonstrated that PRGF represents an autologous source of growth factors able to reduce the healing time of the alveolar mucosa and the discomfort of those patients. These properties are the result of PRGF's precise biological features that result in the following: reduction of duration and intensity of postsurgical pain, acceleration of re-epithelialization of the wound, and reduction of bleeding events and of edema. In conclusion, we showed that using PRGF on patients affected by denture-induced fibrous hyperplasia allows a short healing time, thereby reducing complications and overall improving their quality of life. The aims of this study were to evaluate the influence of PRGF-ENDORET on secondary re-epithelialization in vestibuloplasty after excision of denture irritation fibrous hyperplasia, with an explorative randomized case control trial with 10 patients, 5 patients treated with PRGF and 5 patients with traditional hemostasis, and to analyze differences with simple surgery, considering postoperative rapidity of re-epithelialization, comfort, and discomfort of patients, pain, swelling, and infections.

Factor VIII alloantibody inhibitors: cost analysis of immune tolerance induction vs. prophylaxis and on-demand with bypass treatment.

Development of inhibitors (alloantibodies to exogenous factor VIII) is the most significant treatment complication in patients with haemophilia A. The only proven way to eradicate inhibitors is through immune tolerance induction (ITI), while bypassing agents are typically employed to treat or prevent bleeds in patients with high titre inhibitors. Costs of these approaches have not been well studied. The aim of this study was to compare lifetime costs of treating patients with severe haemophilia A with inhibitors using on-demand or prophylaxis treatment with bypassing agents and ITI. A decision-analytic model was developed to compare the treatment costs and outcomes. Quantitation of the reduction in bleeding events for patients on prophylaxis and after eradication of inhibitors when on ITI and relapse of inhibitors was derived from published studies. Costs were obtained from standard US costing sources and are reported in 2014 US dollars. Costs and outcomes were discounted 3% per annum. Lifetime costs of treating patients with inhibitors are lower for ITI vs. on-demand or prophylaxis. Patients are also projected to live longer, have greater quality-adjusted life-years, and have fewer bleeding events than patients treated on-demand. Treating patients via ITI to eradicate inhibitors may result in lower lifetime costs and greater life-years and quality-adjusted life-years than treating with bypassing agents.

Translational data from adeno-associated virus-mediated gene therapy of hemophilia B in dogs.

Preclinical testing of new therapeutic strategies in relevant animal models is an essential part of drug development. The choice of animal models of disease that are used in these studies is driven by the strength of the translational data for informing about safety, efficacy, and success or failure of human clinical trials. Hemophilia B is a monogenic, X-linked, inherited bleeding disorder that results from absent or dysfunctional coagulation factor IX (FIX). Regarding preclinical studies of adeno-associated virus (AAV)-mediated gene therapy for hemophilia B, dogs with severe hemophilia B (<1% FIX) provide well-characterized phenotypes and genotypes in which a species-specific transgene can be expressed in a mixed genetic background. Correction of the hemophilic coagulopathy by sustained expression of FIX, reduction of bleeding events, and a comprehensive assessment of the humoral and cell-mediated immune responses to the expressed transgene and recombinant AAV vector are all feasible end points in these dogs. This review compares the preclinical studies of AAV vectors used to treat dogs with hemophilia B with the results obtained in subsequent human clinical trials using muscle- and liver-based approaches.

Thrombopoiesis-stimulating agents and myelodysplastic syndromes.

Thrombocytopenia in patients with myelodysplastic syndromes (MDS) is a frequent cause of haemorrhage-related morbidity and mortality, and is associated with increased risk of leukaemic transformation and reduced overall survival. In addition, thrombocytopenia in MDS limits the tolerability and therapeutic efficacy of disease-modifying therapies, such as azacitidine or lenalidomide. The recombinant human erythropoietin (rHuEPO) erythropoiesis-stimulating agents, epoetin and darbepoetin, are an established component of anaemia management in lower-risk MDS. Their success has, in turn, driven the development of haematopoietic growth factors targeting thrombocytopenia. While recombinant thrombopoietin (THPO) proved too immunogenic for clinical use, novel thrombopoiesis-stimulating agents (TSAs) have the potential to reduce bleeding events, decrease dependency on platelet transfusions and extend exposure to disease-modifying therapies. Two TSAs, eltrombopag and romiplostim, have demonstrated benefit in chronic immune thrombocytopenia purpura (ITP) and safety and efficacy data for use of these agents in MDS is growing. However, important safety concerns remain, such as the potential for stimulation of neoplastic myeloid clones by THPO agonists. In this narrative review, we discuss the rationale and biological mechanism for TSAs in MDS, describe the agents currently available and their mechanism of action, and present current clinical data relating to TSA safety and efficacy in the context of MDS.