Higher Incidence Of Bleeding Research Articles

Efficacy and safety of dual antiplatelet therapy after coronary stenting in patients with chronic kidney disease

We compared efficacy and safety of short- (3 or 6 months) versus long-term (≥12 months) dual antiplatelet therapy (DAPT) after drug-eluting stent (DES) implantation, according to the presence of chronic kidney disease (CKD). Patient-level pooled analysis was performed with 7242 patients (87.2% with 2nd generation DES) from 5 randomized controlled trials. In both CKD (1273 patients) and non-CKD (5969 patients) population, the rates of patient-oriented composite outcomes at 1-year (POCO, all-cause death, any myocardial infarction [MI], stroke and TIMI major bleeding) were not different between the short- and long-term DAPT (hazard ratio [HR] 1.19, 95% confidence interval [CI] 0.76-1.86, P=.449 in CKD population; HR 1.14, 95% CI 0.83-1.56, P=.434 in non-CKD population). The rates of coronary thrombotic events (any MI and definite/probable stent thrombosis) also did not differ between short- and long-term DAPT in either CKD or non-CKD population. As for bleeding events, long-term DAPT increased the TIMI major bleeding (HR 2.91, 95% CI 1.31-6.48, P=.009) in non-CKD population. The similar trend was observed with long-term DAPT in CKD population. But it did not reach statistical significance (HR 3.15, 95% CI 0.64-15.63, P=.160). The rates of POCO and coronary thrombotic events were significantly higher in patients with CKD compared with those without CKD, which were not affected by short- or long-term DAPT. Higher bleeding incidence by long-term DAPT was only observed in non-CKD patients but not in CKD patients. Further large scale studies are warranted to confirm our findings.

Low flow extracorporeal CO2 removal in ARDS patients: a prospective short-term crossover pilot study

BackgroundLung protective mechanical ventilation (MV) is the corner stone of therapy for ARDS. However, its use may be limited by respiratory acidosis.This study explored feasibility of, effectiveness and safety of low flow extracorporeal CO2 removal (ECCO2R).MethodsThis was a prospective pilot study, using the Abylcap® (Bellco) ECCO2R, with crossover off-on-off design (2-h blocks) under stable MV settings, and follow up till end of ECCO2R. Primary endpoint for effectiveness was a 20% reduction of PaCO2 after the first 2-h. Adverse events (AE) were recorded prospectively.We included 10 ARDS patients on MV, with PaO2/FiO2 < 150 mmHg, tidal volume ≤ 8 mL/kg with positive end-expiratory pressure ≥ 5 cmH2O, FiO2 titrated to SaO2 88–95%, plateau pressure ≥ 28 cmH2O, and respiratory acidosis (pH <7.25).ResultsAfter 2-h of ECCO2R, 6 patients had a ≥ 20% decrease in PaCO2 (60%); PaCO2 decreased 28.4% (from 58.4 to 48.7 mmHg, p = 0.005), and pH increased (1.59%, p = 0.005). ECCO2R was hemodynamically well tolerated. During the whole period of ECCO2R, 6 patients had an AE (60%); bleeding occurred in 5 patients (50%) and circuit thrombosis in 3 patients (30%), these were judged not to be life threatening.ConclusionsIn ARDS patients, low flow ECCO2R significantly reduced PaCO2 after 2 h, Follow up during the entire ECCO2R period revealed a high incidence of bleeding and circuit thrombosis.Trial registrationhttps://clinicaltrials.gov identifier: NCT01911533, registered 23 July 2013.

Antithrombotic treatment during coronary angioplasty after failed thrombolysis: strategies and prognostic implications. Results of the RESPIRE registry

BackgroundThrombolysis is still used when primary angioplasty is delayed for a long time, but 25%–30% of patients require rescue angioplasty (RA). There are no established recommendations for antithrombotic management in RA. This registry analyzes regimens for antithrombotic management.MethodsA retrospective, multicenter, observational registry of consecutive patients treated with RA at 8 hospitals. All variables were collected and follow-up took place at 6 months.ResultsThe study included 417 patients. Antithrombotic therapy in RA was: no additional drugs 22.3%, unfractionated heparin (UFH) 36.6%, abciximab 15.5%, abciximab plus UFH 10.5%, bivalirudin 5.7%, enoxaparin 4.3%, and others 4.7%. Outcomes at 6 months were: mortality 9.1%, infarction 3.3%, definite or probable stent thrombosis 4.3%, revascularization 1.9%, and stroke 0.5%. Mortality was related to cardiogenic shock, age > 75 years, and anterior location. The stent thrombosis rate was highest with bivalirudin (12.5% at 6 months). The incidence of bleeding at admission was high (14.8%), but most cases were not severe (82% BARC ≤2). Variables independently associated with bleeding were: femoral access (OR 3.30; 95% CI 1.3–8.3: p = 0.004) and post-RA abciximab infusion (OR 2.26; 95% CI 1.02–5: p = 0.04).ConclusionsAntithrombotic treatment regimens in RA vary greatly, predominant strategies consisting of no additional drugs or UFH 70 U/kg. No regimen proved predictive of mortality, but bivalirudin was related to more stent thrombosis. There was a high incidence of bleeding, associated with post-RA abciximab infusion and femoral access.

Major Bleeding with Ibrutinib: More Than Expected

▪Introduction: Ibrutinib is a Bruton's tyrosine kinase inhibitor that has significant activity in treating lymphoma. While approved for patients with Chronic Lymphocytic Leukemia (CLL) and Mantle Cell Lymphoma (MCL), its activity in other lymphomas and solid tumors is under investigation and its use is increasing dramatically. Overall it is well tolerated compared to chemotherapy, but bleeding has emerged as a common adverse event with rates as high as 50% and major bleeding around 3% (Jones, abstract #1990, 2014 ASH Annual Meeting). As the use of ibrutinib increases outside of a clinical trial setting, the rate of major bleeding is likely to rise.Methods: To better understand the risk of bleeding in ibrutinib treated patients, we reviewed all patients at the University of Virginia and satellite clinics who were treated with ibrutinib between January 2012 and May 2016. Patients were required to be treated for at least 1 month with documented follow up for assessment of adverse events. Medical charts were reviewed for age, gender, ibrutinib indication and dose, length of treatment, concurrent medications, blood tests and bleeding events. All forms of anti-platelets and anticoagulants drugs, as well as medications interacting with cytochrome P450 3A4 (3A4), which metabolizes ibrutinib, were recorded. All bleeding events were recorded and graded according the Common Toxicity Criteria for Adverse Events, v4.0. Major bleeding events were reviewed by all investigators.Results: Eighty-nine patients were identified. Eighteen patients were excluded for insufficient follow up leaving 71 patients for analysis. Median age was 73 years old (44-92) with 74% male. The most common indications for treatment were CLL (65%) and MCL (27%). Most patients were treated with either 420mg (64%) or 560mg (21%). Median length of time on ibrutinib was 412 days, most with ongoing use at time of data collection. Seventy percent of patients were also treated with an anti-platelet medication, mostly aspirin for CAD with several patients on multiple anti-platelet medications. Seventeen percent were treated with an anti-coagulant, mostly apixaban for atrial fibrillation. Thirteen percent of patients (9/71) were treated with combined anti-platelet and anti-coagulant medications. Ten percent of patients were treated with a medication that has a moderate or strong interaction with 3A4. Bleeding of any grade occurred in 56% of patients, mostly bruising and epistaxis. Major bleeding, defined as grade 3 or higher, occurred in 18% of patients. Three patients developed major bleeding after an invasive procedure without ibrutinib being held. One patient died as a result of peri-procedural bleeding. Of the 9 patients treated with combined anti-platelet and anti-coagulant therapy, 78% suffered a major bleeding event. Of the ten patients on ibrutinib alone, without concurrent use of an anti-platelet, anti-coagulant or 3A4 drug interaction, no major bleeding events occurred.Conclusion: In this study examining real world use of ibrutinib, the rates of major bleeding are higher than previously reported. Most patients who suffered major bleeding were also treated with an anti-coagulant and/or anti-platelet medication. As the use of ibrutinib increases outside of clinical trials, a careful review of medications should be performed in addition to adherence to perioperative drug withholding guidelines. Patients requiring anti-coagulant and/or anti-platelet medications while on ibrutinib need careful consideration of the risks and benefits given the higher incidence of bleeding in this population. [Display omitted] DisclosuresPortell:AbbVie: Research Funding; Roche/Genentech: Research Funding; Infinity: Research Funding; Acerta: Research Funding. Williams:Janssen and Pharmacyclics: Research Funding; University of Virginia: Employment.

The clinical outcomes of triple antiplatelet therapy versus dual antiplatelet therapy for high-risk patients after coronary stent implantation: a meta-analysis of 11 clinical trials and 9,553 patients.

BackgroundThe optimal antiplatelet regimen after in-coronary intervention among patients presenting with complex coronary artery lesions or acute coronary syndrome (ACS) has remained unclear. This study sought to evaluate the clinical outcomes of triple antiplatelet treatment (TAPT) (cilostazol added to aspirin plus clopidogrel) in these patients.MethodsThe PubMed, EMBASE, MEDLINE, and other Internet sources were searched for relevant articles. The primary end point was major adverse cardiac events (MACE), including all-cause mortality, myocardial infarction, and target vessel revascularization. The incidence of definite/probable stent thrombosis and bleeding were analyzed as the safety end points.ResultsEleven clinical trials involving 9,553 patients were analyzed. The risk of MACE was significantly decreased following TAPT after stent implantation in the ACS subgroup (odds ratio [OR]: 0.72; 95% confidence interval [CI]: 0.61–0.85; P<0.001), which might mainly result from the lower risk of all-cause mortality in this subset (OR: 0.62; 95% CI: 0.48–0.80; P<0.001). The risk of bleeding was not increased with respect to TAPT.ConclusionTAPT after stent implantation was associated with feasible benefits on reducing the risk of MACE, especially on reducing the incidence of all-cause mortality among patients suffering from ACS, without higher incidence of bleeding. Larger and more powerful randomized trials are still warranted to prove the superiority of TAPT for such patients.

Risk of Ischemic Stroke, Hemorrhagic Stroke, Bleeding, and Death in Patients Switching from Vitamin K Antagonist to Dabigatran after an Ablation.

BackgroundSafety regarding switching from vitamin K antagonist (VKA) to dabigatran therapy in post-ablation patients has never been investigated and safety data for this is urgently needed. The objective of this study was to examine if switch from VKA to dabigatran increased the risk of stroke, bleeding, and death in patients after ablation for atrial fibrillation.MethodsThrough the Danish nationwide registries, patients with non-valvular atrial fibrillation undergoing ablation were identified, in the period between August 22nd 2011 and December 31st 2015. The risk of ischemic stroke, hemorrhagic stroke, bleeding, and death, related to switching from VKA to dabigatran was examined using a multivariable Poisson regression model, where Incidence rate ratios (IRR) were estimated using VKA as reference.ResultsIn total, 4,236 patients were included in the study cohort. The minority (n = 470, 11%) switched to dabigatran in the follow up period leaving the majority (n = 3,766, 89%) in VKA treatment. The patients in the dabigatran group were older, were more often males, and had higher CHA2DS2-VASc, and HAS-BLED scores. The incident rates of bleeding and death were almost twice as high in the dabigatran group compared with the VKA group. When adjusting for the individual components included in the CHA2DS2-VASc and HAS-BLED scores, the multivariable Poisson analyses yielded a non-significant IRR (95%CI) of 1.64 (0.72–3.75) for bleeding and of 1.41 (0.66–3.00) for death associated with the dabigatran group, compared to the VKA group. A significant increased risk of bleeding was found in the 110mg bid group with an IRR (95%CI) of 4.49(1.40–14.5).ConclusionShifting from VKA to dabigatran after ablation was associated with twice as high incidence of bleeding compared to the incidence in patients staying in VKA treatment. The only significant increased risk found in the adjusted analyses was for bleeding with 110mg bid dabigatran and not for 150mg bid. Since there was no dose-response for bleeding, the switch from VKA to dabigatran in itself was not a risk factor for bleeding.

Transcatheter Aortic Valve Replacement in Women Versus Men (from the US CoreValve Trials)

Treatment for severe symptomatic aortic stenosis has changed significantly in recent years due to advances in transcatheter aortic valve replacement (TAVR). Recent studies with the CoreValve prosthesis have demonstrated superior results compared with surgical aortic valve replacement in patients at increased risk for surgery, but there are limited data on gender-related differences in patient characteristics and outcomes with this device. We compared baseline characteristics and clinical outcomes in women and men undergoing TAVR with the CoreValve prosthesis. A total of 3,687 patients (1,708 women and 1,979 men) were included. At baseline, women tended to be slightly older and to have increased frailty, but they had fewer cardiac co-morbidities, higher left ventricular systolic function, less coronary artery disease, and fewer previous strokes. All-cause mortality was 5.9% for women and 5.8% for men at 30days (p= 0.87) and 24.1% and 21.3%, respectively, at 1year (p= 0.08). The incidence of stroke was 5.7% in women and 4.0% in men at 30days (p= 0.02) and 9.3% and 7.7%, respectively, at 1year (p= 0.05). Women had a higher incidence of bleeding, including more life-threatening bleeds, and a greater incidence of major vascular complications than men at 30days. Device success was achieved in 86.9% of women and 86.1% of men (p= 0.50). In conclusion, although there were significant baseline differences and procedure-related complications between women and men undergoing TAVR with the CoreValve prosthesis, this analysis found no significant difference in 30-day or 1-year mortality.

Antiplatelet therapy versus observation in low-risk essential thrombocythemia with a CALR mutation.

The role of antiplatelet therapy as primary prophylaxis of thrombosis in low-risk essential thrombocythemia has not been studied in randomized clinical trials. We assessed the benefit/risk of low-dose aspirin in 433 patients with low-risk essential thrombocythemia (271 with a CALR mutation, 162 with a JAK2(V617F) mutation) who were on antiplatelet therapy or observation only. After a follow up of 2215 person-years free from cytoreduction, 25 thrombotic and 17 bleeding episodes were recorded. In CALR-mutated patients, antiplatelet therapy did not affect the risk of thrombosis but was associated with a higher incidence of bleeding (12.9 versus 1.8 episodes per 1000 patient-years, P=0.03). In JAK2(V617F)-mutated patients, low-dose aspirin was associated with a reduced incidence of venous thrombosis with no effect on the risk of bleeding. Coexistence of JAK2(V617F)-mutation and cardiovascular risk factors increased the risk of thrombosis, even after adjusting for treatment with low-dose aspirin (incidence rate ratio: 9.8; 95% confidence interval: 2.3-42.3; P=0.02). Time free from cytoreduction was significantly shorter in CALR-mutated patients with essential thrombocythemia than in JAK2(V617F)-mutated ones (median time 5 years and 9.8 years, respectively; P=0.0002) and cytoreduction was usually necessary to control extreme thrombocytosis. In conclusion, in patients with low-risk, CALR-mutated essential thrombocythemia, low-dose aspirin does not reduce the risk of thrombosis and may increase the risk of bleeding.

(123) - Heparin-Free Off-Pump LVAD Implantation Reduces Early Adverse Events Compared with On-Pump Implantation

Left ventricular assist device implantation is associated with a relatively high incidence of bleeding and right ventricular failure (RVF). These adverse events increase resource use, hospital stay and compromise survival. An off-pump implant technique without using intra-operative systemic heparin was developed to reduce these adverse events. Early outcomes of patients implanted with the HeartWare HVAD using cardiopulmonary bypass (CPB) or the heparin-free off-pump implant technique were compared. A retrospective analysis of 57 consecutive patients who underwent HeartWare HVAD implantation from October 2009 to October 2015 was carried out. Demographic and perioperative clinical variables were analyzed using Fisher’s exact test and Wilcoxon Rank-Sum test. HeartWare HVADs were implanted using CPB (Group CPB, n = 34) or the heparin free off pump technique (Group HFOP, n = 23); in the latter group, 7 were performed with a full sternotomy and 16 with minimal access using hemi-sternotomy plus left anterior thoracotomy. All patients required inotropic therapy for stage-D heart failure. Group HFOP had significantly higher pre-operative mean transpulmonary gradient and higher INTERMACS profile. In the peri-implant period, 13 (56.5%) patients in the HFOP group did not require Red Cell transfusion and none required FFP or platelet transfusion. Post-operatively, Group CPB had significantly higher rate of hemorrhage (P=0.007), chest re-exploration (P=0.002), Red Cell (P=0.013) and blood products (P=0.002) transfusion. There was a trend towards shorter ICU stay and lower incidence of RVF in the HFOP group. Overall 30-day and 1-year survivals were 96.4% and 81% respectively with no difference between groups. HFOP implantation of HVAD in patients with higher INTERMACS profile is associated with less bleeding, blood product usage and a trend towards less RV failure and shorter ICU stay. Use of this technique should be further explored in a larger clinical trial.Tabled 1HVAD TableClinical VariablesGroup HFOP (N= 23) Mean ± SDGroup CPB (N=34) Mean ± SDP-ValueAge50.3 ± 15.048.3 ± 9.70.576Sex (Male)82.6%76.5%0.744Dilated cardiomyopathy43.7%56.2%0.796Preoperative TPG (mm Hg)15.7±4.612.6 ± 4.10.012INTERMACS Profile2.3±0.481.8 ±0.690.018Inotropes duration (days)7.2 ± 6.58.8 ± 6.70.357Red blood cells (ml)399.3 ± 693.71992.5 ±3488.60.013Platelets (ml)0315.1 ± 410.90.005Fresh frozen Plasma (ml)0320.9 ± 559.00.002Re-exploration of chest4.3%41.2%0.002Post-operative hemorrhage (ml)202.4 ± 105.2476.2 ± 239.40.007Need for RVAD4.3%23.5%0.069Need of Ventilation (Hours)33.9 ± 35.345.9 ± 33.80.215ICU stay (days)8.8 ± 5.312.2 ± 7.60.0595Late drive line infection17.0%20.5%1Late bleeding complications8.7%14.7%0.68930-day mortality4.3%2.9%1One year survival82.6%79.4%1 Open table in a new tab

Long-term use of ticagrelor in patients with prior heart attack: ticagrelor plus aspirin versus aspirin monotherapy

ABSTRACTReview of: Bonaca MP, Bhatt DL, Cohen M, et al. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med. 2015;372:1791-1800.This Practice Pearl reviews the recent study Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared With Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54 (PEGASUS-TIMI 54). It challenges the current standard of care of 12 months of dual antiplatelet followed by aspirin indefinitely. The study demonstrated that patients who received ticagrelor, either the 60 mg or 90 mg twice daily plus aspirin, showed a decreased risk of cardiovascular death, myocardial infarction, or stroke. The PEGASUS-TIMI 54 trial also proved that the benefit of ticagrelor was seen early and continued to accrue over time, with a median of 33 months of follow-up, meaning that the benefit persists over time. It is important to note that both doses of the ticagrelor were associated with higher incidence of bleeding, but the rates of fatal bleeding did not show any difference between the ticagrelor or placebo.

Long-term prognostic role of uric acid in patients with ST-elevation myocardial infarction and renal dysfunction.

Patients with renal impairment have decreased excretion of uric acid, thus being particularly prone to having elevated serum uric acid concentrations. No data are available on the long-term prognostic role of uric acid in patients with ST-elevation myocardial infarction (STEMI) and renal dysfunction, submitted to percutaneous coronary intervention (PCI). We therefore prospectively assessed, in 329 patients with STEMI and renal dysfunction (admission estimated glomerular filtration rate <60 ml/min/1.73 m), all submitted to PCI, whether uric acid levels are associated with increased mortality at 1-year postdischarge follow-up.Patients in the third tertile of uric acid showed a higher BMI (P = 0.014), a higher incidence of hypertension (P = 0.029), and two or more comorbidities (P = 0.034). The highest incidence of bleeding and of acute kidney injury was detectable in patients in the third tertile (P = 0.011 and P < 0.001, respectively) who showed the highest mortality rate at 1-year postdischarge follow-up (P = 0.008). At Cox regression analysis, uric acid was an independent predictor of 1-year postdischarge mortality (hazard ratio 1.26, 95% confidence interval 1.06-1.51, P = 0.011).In STEMI patients with estimated glomerular filtration rate below 60 ml/min/1.73 m treated with PCI, uric acid helps in identifying a subset of patients at a higher risk of bleeding and acute kidney injury. Increased uric acid is an independent prognostic risk factor for 1-year mortality. Further studies performed in larger cohorts of patients are needed to confirm our findings and to evaluate whether lowering uric acid in these patients is beneficial.

Comparison of conventional compressive dressings vs. wristband devices after catheterization by radial approach

ABSTRACT Background Wristband devices used in the compression of the radial puncture site add cost to the procedure and have not been adequately compared with conventional compressive dressings. This study evaluated the effectiveness and safety of both forms of hemostasis in patients undergoing coronary angiography and/or percutaneous coronary intervention in daily practice. Methods A prospective, multicenter, nonrandomized study, which included consecutive patients who underwent procedures through radial access. The type of compression was at the interventionist's discretion and the availability of wristband devices. The main objective was to compare the patency of the radial artery on the 7 th day after the procedure, measured by Doppler. Secondarily, the authors evaluated the occurrence of bleeding/hematoma at the puncture site during compression, after removal of the device and on the 7 th day after the procedure. Results This study evaluated 528 patients, 416 using conventional compressive dressings and 112 using wristband devices. When the sheath was removed and soon after its removal, a higher incidence of bleeding in the conventional compressive dressings group was observed (13.4% vs. 0%; p p = 0.20). Conclusions The use of wristband devices for radial artery hemostasis did not result in higher rates of late arterial patency when compared to conventional compressive dressings.

Clinical Manifestations and Risk Factors for Complications of Philadelphia Chromosome-Negative Myeloproliferative Neoplasms.

Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders characterized by proliferation of one or more myeloid lineages. Polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) are classical Philadelphia chromosome (Ph)-negative MPN that have a Janus Kinase 2 (JAK2) mutation, especially JAK2V617F in the majority of patients. The major complications of Ph-negative MPNs are thrombosis, hemorrhage, and leukemic transformation. To study clinical manifestations including symptoms, signs, laboratory findings, and JAK2V617F mutations of Ph-negative MPN (PV, ET and PMF) as well as their complications. All Ph-negative MPN (PV, ET and PMF) patients who attended the Hematology Clinic at Maharaj Nakorn Chiang Mai Hospital from January, 1 2003 through December, 31 2013 were retrospectively reviewed for demographic data, clinical characteristics, complete blood count, JAK2V617F mutation analysis, treatment, and complications. One hundred and fifty seven patients were included in the study. They were classified as PV, ET and PMF for 68, 83 and 6 with median ages of 60, 61, and 68 years, respectively. JAK2V617F mutations were detected in 88%, 69%, and 100% of PV, ET and PMF patients. PV had the highest incidence of thrombosis (PV 29%, ET 14%, and PMF 0%) that occurred in both arterial and venous sites whereas PMF had the highest incidence of bleeding (PMF 17%, ET 11%, and PV 7%). During follow up, there was one ET patient that transformed to acute leukemia and five cases that developed thrombosis (three ET and two PV patients). No secondary myelofibrosis and death cases were encountered. Ph-negative MPNs have various clinical manifestations. JAK2V617F mutations are present in the majority of PV, ET, and PMF patients. This study confirmed that thrombosis and bleeding are the most significant complications in patients with Ph-negative MPN.

Role of thrombocytopenia in radiation-induced mortality and review of therapeutic approaches targeting platelet regeneration after radiation exposure

Preclinical studies on irradiated animals show that thrombocytopenia can play a role in radiation mortality, particularly in animals receiving minimal supportive care. These findings are consistent with anecdotal evidence from the atomic bombings, where bleeding complications were noted often in patients. To evaluate the role of thrombocytopenia and hemorrhage in radiation-induced mortality, a review was conducted of publicly available pathology reports of patients who died following radiation exposure. Of the 42 reports identified with reasonably complete information, exposures resulted from nuclear detonation, contact with improperly disposed sources, radiotherapy, or industrial accidents. Consistent with animal data, a high incidence of bleeding was noted in the autopsy reports of the victims. Also presented is a review of animal model data on the use of various forms of thrombopoietin (TPO) as a treatment for hematopoietic acute radiation syndrome (ARS). Although animal studies suggested these approaches would increase platelet levels following lethal irradiation, their clinical development was halted due to lack of significant efficacy for chemotherapy-induced thrombocytopenia and safety concerns. Because there is currently no approved treatment stockpiled for radiation-induced thrombocytopenia, second-generation TPO mimetics and other novel platelet-promoting agents should be developed for this indication.

Management of isolated calf vein thrombosis in cancer patients

The treatment of isolated calf vein thrombosis remains widely debated. This study highlights the characteristics of isolated calf vein thrombosis in cancer patients and compares to isolated calf vein thrombosis in patients without history of cancer. Between July 2013 and April 2014, a retrospective chart review of consecutive patients with isolated calf vein thrombosis was performed recording patient risk factors, ultrasound characteristics of the thrombus, treatment modalities, long-term recurrence of venous-thromboembolism, incidence of bleeding, and mortality. Of 131 patients with isolated calf vein thrombosis, 53 (40.1%) had history of cancer. Isolated calf vein thrombosis occurred at an older age in cancer patients (66.7 vs 58.5 years, p = 0.004). The anatomical characteristics of isolated calf vein thrombosis on ultrasound were comparable in both groups. Isolated calf vein thrombosis in cancer patients was less likely to be treated with anticoagulation (60.4% vs 80.8%, p = 0.018). However, a trend towards higher incidence of bleeding after initiation of anticoagulation for isolated calf vein thrombosis in cancer patients (11.3% vs 6.4%, p = 0.351) was noted. Mortality in cancer patients was higher (37.7% vs 9.00%, p < 0.001) but was unrelated to isolated calf vein thrombosis or its treatment. In conclusion, the risks of bleeding seem to exceed the benefits of anticoagulation in approximately 50% of cancer patients with isolated calf vein thrombosis. The management of isolated calf vein thrombosis does not seem to impact the survival of cancer patients.

Bivalirudin in stable angina and acute coronary syndromes.

A parenteral anticoagulant is indicated in patients with acute coronary syndromes. Which anticoagulant should be preferred in each setting is not clearly established. Bivalirudin administration was considered in acute coronary syndromes after several clinical trials showed decreased bleeding risk with its use compared with the association of unfractionated heparin (UFH) with glycoprotein IIb/IIIa inhibitors (GPIs). Most recent data demonstrate that the bleeding benefit identified in the previous studies was not due to bivalirudin's properties but to higher bleeding incidence in the comparator arm due to the disproportional use of GPIs with heparin. This paper reviews clinical evidence on bivalirudin as anticoagulant in stable angina and acute coronary syndromes.

The efficacy and safety of mechanical hemodynamic support in patients undergoing high-risk percutaneous coronary intervention with or without cardiogenic shock: Bayesian approach network meta-analysis of 13 randomized controlled trials

BackgroundStudies have reported conflicting results regarding efficacy of mechanical hemodynamic support using intra-aortic balloon pump (IABP) or percutaneous ventricular assisted device (pVAD) in patients undergoing high-risk PCI. We performed a Bayesian network meta-analysis comparing the safety and efficacy of mechanical hemodynamic support devices and medical therapy (MT). Methods and resultsRCTs comparing overall mortality of IABP versus MT or IABP versus pVAD in high-risk PCI populations were included. The primary endpoint was overall mortality, using the longest available follow-up in each study. This analysis included 2843 patients from 13 trials. In network meta-analysis, overall survival benefit was not significant with IABP (RR 0.84, 95% CrI 0.56–1.24) or pVAD (RR 0.95, 95% CrI 0.42–2.06), compared with MT. IABP or pVAD also did not show early survival benefit compared with MT. In terms of bleeding, pVAD was the worst (versus IABP: RR 29.4, 95% CrI 5.99–221.0; versus MT: RR 41.7, 95% CrI 8.19–330.0), which was mainly driven by the higher incidence of bleeding in the ECMO and TandemHeart, while IABP was worse than MT (RR 1.41, 95% CrI 1.01–2.08). The incidence of acute limb ischemia or vascular complication was not different between treatment groups. ConclusionsIn this meta-analysis, routine elective use of IABP or pVAD did not reduce mortality, while it increased bleeding, compared with MT in high-risk PCI population or even in the patients with cardiogenic shock. Thoughtful selection of appropriate patients and balancing the risk and benefit should be the prerequisites to the use of mechanical hemodynamic support devices.

Abstract 20119: Incidence and Predictors of Left Ventricular Thrombus in ST Elevation Myocardial Infarction

Introduction: Anticoagulation with coumadin is often employed after anterior ST-segment elevation myocardial infarction (STEMI) complicated by left ventricular (LV) dysfunction to prevent LV thrombus and cardioembolic events. However, the combination of dual antiplatelet therapy used for coronary stents and coumadin has been repeatedly shown to have a high incidence of bleeding. The current guidelines give coumadin a class II recommendation and support an individualized approach to treatment. Hypothesis: Determining the incidence and predictors of LV thrombus in a contemporary STEMI population at high risk for LV thrombus may assist in clinical decision making. Methods: Anterior STEMI patients at our institution between 2006 and 2013 treated with primary percutaneous intervention (PCI) that had an echocardiogram performed within 1 week and an ejection fraction of less than 40% or less than 50% with anterior apical akinesis were retrospectively identified. 687 patients with anterior STEMI were screened and 310 met inclusion. Demographic, clinical, and angiographic data was extracted from the medical record. Patients were categorized in 2 groups according to echocardiographic findings (no LV thrombus or probable/definite LV thrombus). The groups were compared by chi squared or T-test where appropriate. Logistic regression analysis was performed. Results: The mean age of the study population was 61.8% and 71.5% were male. The incidence of LV thrombus was 15% (n=263 no thrombus; n=47 probable/definite thrombus). Patients with LV thrombus were less likely to have hyperlipidemia, and more likely to have post procedure TIMI 0-1 flow and no stent use compared to patient with no LV thrombus. After adjustment, variables associated with LV thrombus risk were cardiac arrest (OR 4.06, 1.3-12.7), unfractionated heparin post PCI (2.43, 1.16-5.1), and stent use (DES 0.22, .06-.77, BMS 0.23 .07-.75, compared to balloon angioplasty). Conclusions: The incidence of LV thrombus in at risk STEMI patients remains high in contemporary practice. Development of a clinical risk score is limited by the lack of a sufficient number of predictive variables. Further investigation is needed to determine the optimal anticoagulation strategy in these patients.

Safety of Prasugrel in Indian patients – Multicentric registry of 1000 cases

BackgroundClopidogrel has been the only available antiplatelet drug used along with aspirin in patients of ACS. In recent years 2 new antiplatelet drugs (Prasugrel and Ticagrelor) have become available. Prasugrel in the dose of 10 mg OD has been found to be more efficacious but with increased risk of major bleeding. For this reason it has not gained widespread usage in ACS patients undergoing PCI. There are no systematic data on the use of Prasugrel in Indian population. MethodThis is a prospective, multicentric, hospital registry of 1000 patients with ACS undergoing PCI who were administered Prasugrel. The primary safety endpoint of this study was major and minor bleeding while the efficacy endpoint is the composite of CV death, nonfatal MI, nonfatal stroke up to 30 days after PCI. Patients with high bleeding risk were excluded. ResultsMost patients (91%) received loading dose of Prasugrel along with the maintenance dose getting according to the defined protocol. Patients were followed up to 30 days post procedure. Primary efficacy end point was reached in 3 patients only with two of them dying due to possible stent thrombosis and the third requiring revascularization of the target vessel for stent thrombosis. One major and 19 minor bleeding complications were recorded, with access site bleeding in 0.7% & non-access site bleeding in 1.2% of the subjects. ConclusionPrasugrel was found to be effective & not associated with a high incidence of bleeding in the high risk ACS patients when those at a high bleeding risk were excluded.

Risk of Gastrointestinal Bleeding with Dabigatran: A Head-to-Head Comparative Study with Rivaroxaban

Introduction: The risk of gastrointestinal (GI) bleeding of dabigatran and rivaroxaban is relatively unexplored. The aim of our study was to compare this risk in both drugs. Methods: We examined the medical records of patients on either dabigatran or rivaroxaban from October 2010 to April 2013 in two hospitals. Results: A total of 374 patients (147 rivaroxaban vs. 227 dabigatran) were identified. GI bleeding occurred in 5.3% in the dabigatran when compared to 4.8% in the rivaroxaban group (p = 0.8215). Multivariate analysis showed that the odds of GI bleeding while on dabigatran for ≤40 days when compared to ≥40 days was 8.3 (p < 0.0001). In the rivaroxaban group, patients who were on the drug for ≤40 days had a higher incidence of bleeding when compared to those >40 days (OR = 2.8, p = 0.023). Concomitant use of antiplatelets (single or dual) or non-steroidal anti-inflammatory drugs was not associated with increased bleeding in the dabigatran group; however, the use of dual antiplatelet agents with rivaroxaban was associated with an increased risk of GI bleeding (OR = 7.4, p = 0.0378). Prior GI bleeding had a higher risk of bleeding in the rivaroxaban group (OR = 15.5, p = 0.0002). Conclusion: Dabigatran was not associated with a higher incidence of GI bleeding. Both drugs had a higher bleeding risk in the first 40 days.