Bleeding Academic Research Consortium Classification Research Articles

Chronic Kidney Disease and Third-Generation P2Y12 Inhibitors Use in Patients With Acute Coronary Syndrome: Impact on the Prognosis at 1 Year.

Chronic kidney disease (CKD) is associated with worse clinical outcomes in patients with acute coronary syndrome. However, they are underrepresented in clinical trials. We aimed to investigate differences in prognosis of acute coronary syndrome patients with and without CKD, focusing on the use of novel P2Y12 receptor inhibitors. This multicenter registry involved patients with acute coronary syndrome from 3 tertiary institutions. After excluding anticoagulated patients and patients on antiplatelet monotherapy, 1280 patients remained. During 1 year of follow-up, we recorded all major adverse cardiovascular events (composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal ischemic stroke), bleeds (Bleeding Academic Research Consortium classification) and deaths. Of 1280 patients, 325 (25.4%) had CKD; 55.5% of non-CKD patients and 22.7% of CKD patients were prescribed novel P2Y12 inhibitors. During follow-up, CKD patients under novel P2Y12 inhibitors showed a not statistically significant lower mortality and incidence of thrombotic events than clopidogrel-treated ones. In contrast, non-CKD patients taking novel P2Y12 inhibitors had better outcomes in terms of major adverse cardiovascular events (4.72 vs 9.41; P=.006), all-cause mortality (1.32 vs 4.24; P=.006), and severe bleeding events (Bleeding Academic Research Consortium 3-5) (0.94 vs 2.82; P=.030), without differences for any bleeding (8.11 vs 8.47; P=.849). Bleeding risk was not increased by using third-generation P2Y12 inhibitors in either group of patients. In conclusion, the use of third-generation P2Y12 inhibitors among non-CKD patients was associated with better outcomes. CKD patients receiving third-generation P2Y12 inhibitors treatment showed no statistically significant lower mortality and thrombotic events. Bleeding risk was not increased with the use of third-generation P2Y12 inhibitors in either group of patients.

Disparities in the Estimation of Glomerular Filtration Rate According to Cockcroft‐Gault, Modification of Diet in Renal Disease‐4, and Chronic Kidney Disease Epidemiology Collaboration Equations and Relation With Outcomes in Patients With Acute Coronary Syndrome

BackgroundA simple method to assess renal function is the estimated glomerular filtration rate, and it shows prognostic implications. However, it remains unknown which equation should be used in patients with acute coronary syndrome. We compared the ability and correlation of the Cockcroft‐Gault, Modification of Diet in Renal Disease‐4 (MDRD‐4), and Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) equations and their predictive performance for major adverse cardiovascular events, all‐cause mortality, and major bleeding in a cohort of patients with acute coronary syndrome.Methods and ResultsMulticenter prospective registry involving 1699 consecutive patients with acute coronary syndrome from 3 tertiary institutions. At entry, renal function was assessed using the Cockcroft‐Gault, MDRD‐4, and CKD‐EPI‐creatinine equations. During 12 months of follow‐up, we recorded all major adverse cardiovascular events (composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal ischemic stroke), bleeding events (Bleeding Academic Research Consortium classification), and all‐cause mortality. Receiver operating characteristic curve comparisons demonstrated that Cockcroft‐Gault equation had higher predictive ability compared with MDRD‐4 equation for major adverse cardiovascular events (0.651 versus 0.616; P=0.023), major bleeding (0.600 versus 0.551; P=0.005), and all‐cause mortality (0.754 versus 0.717; P=0.033), as well as higher predictive ability compared with CKD‐EPI equation for major bleeding (0.600 versus 0.564; P=0.018). Integrated discrimination improvement and net reclassification improvement analyses showed superior discrimination and reclassification of Cockcroft‐Gault equation. Decision curve analyses graphically demonstrated higher net benefit and clinical usefulness of the Cockcroft‐Gault equation in comparison with MDRD‐4 and CKD‐EPI equations.ConclusionsIn patients with acute coronary syndrome, the Cockcroft‐Gault equation presented superior predictive ability for major adverse cardiovascular events, major bleeding, and all‐cause mortality compared with MDRD‐4 equation, and superior predictive ability for major bleeding compared with CKD‐EPI equation. The Cockcroft‐Gault equation also showed higher net benefit and clinical usefulness.

D-dimer predicts bleeding complication in out-of-hospital cardiac arrest resuscitated with ECMO

PurposeIn out-of-hospital cardiac arrest (OHCA) patients resuscitated with veno-arterial extracorporeal membrane oxygenation (VA-ECMO), known as extracorporeal cardiopulmonary resuscitation (ECPR), bleeding is a common complication. The purpose of this study was to assess the risk factors for bleeding complications in ECPR patients. MethodsWe retrospectively analyzed the data for OHCA patients admitted to our hospital and resuscitated with ECPR between October 2009 and December 2016. We compared patients with and without major bleeding (i.e. the Bleeding Academic Research Consortium class≥3 bleeding) within 24h of hospital admission. Patients, whose bleeding complication was not evaluated, were excluded. ResultsDuring the study period, 133 OHCA patients were resuscitated with ECPR, of whom 102 (77%) were included. In total, 71 (70%) patients experienced major bleeding. There were significant differences in age (median 65 vs. 50years, P<0.001), prior antiplatelet therapy (25% vs. 3%, P=0.008), hemoglobin (median 11.6 vs. 12.6g/dL, P=0.003), platelet count (median 125 vs. 155×103/μL, P=0.001), and D-dimer levels on admission (median 18.8 vs. 6.7μg/mL, P<0.001) among patients with and those without major bleeding. Multivariate analysis showed significant associations between major bleeding and D-dimer levels (odds ratio, 1.066; 95% confidence interval, 1.018–1.116). Area under receiver-operating characteristic curve, which describes the accuracy of D-dimer levels in predicting major bleeding, was 0.76 (95% confidence interval, 0.66–0.87). ConclusionD-dimer levels may predict major bleeding in ECPR patients, suggesting that hyperfibrinolysis may be related to bleeding.

Minor Nonintracranial Hemorrhage and Poor Prognosis among Stroke Patients Undergoing Intravenous Thrombolysis

Whether nonintracranial hemorrhage (NICH) associated with intravenous thrombolysis (IVT) is a predictor of intracranial hemorrhage (ICH) and poor prognosis is ambiguous. We sought to analyze the rate of NICH and the relationship between NICH and poor outcome in the ischemic stroke population undergoing IVT. This is a single-center, hospital-based prospective study. All ischemic stroke patients undergoing IVT between December 2015 and November 2016 were included. NICH was defined according to the criteria of the Bleeding Academic Research Consortium (BARC). ICH associated with IVT was defined based on the European Cooperative Acute Stroke Study II definition. On the basis of the modified Rankin Scale (mRS), 90-day outcome was divided into favorable outcome (mRS score 0-1) versus unfavorable outcome (mRS score 2-6) and independency (mRS score 0-2) versus dependency and death (mRS score 3-6). A total of 212 patients undergoing IVT were included in the analysis. Forty-five NICH events were reported in 42 patients (19.8%). Older age was independently associated with NICH (P = .049, odds ratio [OR] = .97, 95% confidence interval [CI] .94-1.0). Neither NICH with BARC class 1 or higher (P = .56, OR = .61, 95% CI .11-3.24) nor NICH with BARC class 2 or higher (P = .87, OR = 1.19, 95% CI .14-10.23) was associated with ICH. NICH with BARC class 1 or higher was not associated with unfavorable outcome (P = .67, OR = 1.17, 95% CI .56-2.45) and dependence and death (P = .47, OR = .72, 95% CI .30-1.75), neither was NICH with BARC class 2 or higher (P = .97, OR = 1.02, 95% CI .46-2.27 and P = .30, OR = .59, 95% CI .22-1.62). NICH was common among ischemic stroke populations receiving IVT. NICH with BARC class 2 or lower was not associated with ICH and poor outcome.

Benefit of switching dual antiplatelet therapy after acute coronary syndrome: the TOPIC (timing of platelet inhibition after acute coronary syndrome) randomized study.

Newer P2Y12 blockers (prasugrel and ticagrelor) demonstrated significant ischaemic benefit over clopidogrel after acute coronary syndrome (ACS). However, both drugs are associated with an increase in bleeding complications. The objective of the present study was to evaluate the benefit of switching dual antiplatelet therapy (DAPT) from aspirin plus a newer P2Y12 blocker to aspirin plus clopidogrel 1 month after ACS. We performed an open-label, monocentric, and randomized trial. From March 2014 to April 2016, patients admitted with ACS requiring coronary intervention, on aspirin and a newer P2Y12 blocker and without adverse event at 1 month, were assigned to switch to aspirin and clopidogrel (switched DAPT) or continuation of their drug regimen (unchanged DAPT). The primary outcome was a composite of cardiovascular death, urgent revascularization, stroke and bleeding as defined by the Bleeding Academic Research Consortium (BARC) classification ≥2 at 1 year post ACS. Six hundred and forty six patients were randomized and 645 analysed, corresponding to 322 patients in the switched DAPT and 323 in the unchanged DAPT group. The primary endpoint occurred in 43 (13.4%) patients in the switched DAPT group and in 85 (26.3%) patients in the unchanged DAPT (HR 95%CI 0.48 (0.34-0.68), P < 0.01). No significant differences were reported on ischaemic endpoints, while BARC ≥ 2 bleeding occurred in 13 (4.0%) patients in the switched DAPT and in 48 (14.9%) in the unchanged DAPT group (HR 95%CI 0.30 (0.18-0.50), P < 0.01). A switched DAPT is superior to an unchanged DAPT strategy to prevent bleeding complications without increase in ischaemic events following ACS.

Should a prolonged duration of dual anti-platelet therapy be recommended to patients with diabetes mellitus following percutaneous coronary intervention? A systematic review and meta-analysis of 15 studies.

BackgroundThis study aimed to compare the adverse clinical outcomes associated with a short and a prolonged duration of Dual Anti-Platelet Therapy (DAPT) in patients with Diabetes Mellitus (DM) after undergoing Percutaneous Coronary Intervention (PCI).MethodsMedline/PubMed, EMBASE and the Cochrane library were searched for studies comparing the short and prolonged DAPT use in patients with DM. Adverse outcomes were considered as the clinical endpoints in this analysis. Odds Ratios (OR) with 95 % Confidence Intervals (CI) were used to express the pooled effect on discontinuous variables and the pooled analyses were performed with RevMan 5.3.ResultsFifteen studies with a total number of 25,742 patients with DM were included in this current analysis which showed no significant differences in primary endpoints, net clinical outcomes, myocardial infarction and stroke with OR: 1.03, 95 % CI: 0.65–1.64; P = 0.90, OR: 0.96, 95 % CI: 0.69–1.34; P = 0.81, OR: 0.85, 95 % CI: 0.70–1.04; P = 0.12 and OR: 0.94, 95 % CI: 0.65–1.36; P = 0.75 respectively. Revascularization was also similar between these 2 groups of patients with DM. However, even if mortality favored prolonged DAPT use, with OR: 0.87, 95 % CI: 0.76–1.00; P = 0.05, the result only approached significance. Also, stent thrombosis insignificantly favored a prolonged DAPT duration with OR: 0.56, 95 % CI: 0.27–1.17; P = 0.12. Thrombolysis In Myocardial Infarction (TIMI) defined major and minor bleeding were not significantly different in these diabetic patients with OR: 0.91, 95 % CI: 0.60–1.37; P = 0.65 and OR: 1.08, 95 % CI: 0.62–1.91; P = 0.78 respectively. However, bleeding defined by the Bleeding Academic Research Consortium (BARC) classification was significantly higher with a prolonged DAPT use in these diabetic patients with OR: 1.92, 95 % CI: 1.58–2.34; P < 0.00001.ConclusionFollowing PCI, a prolonged DAPT use was associated with similar adverse clinical outcomes but with a significantly increased BARC defined bleeding compared to a short term DAPT use in these patients with DM. However, even if mortality and stent thrombosis favored a prolonged DAPT use, these outcomes only either reached statistical significance or were insignificant respectively, showing that a clear decision about recommending a prolonged duration of DAPT to patients with DM might not be possible at this moment, warranting further research in this particular subgroup.

Effect of Preprocedural Thrombocytopenia on Prognosis After Percutaneous Coronary Intervention

ObjectiveTo assess early and late outcomes, including bleeding, in patients with thrombocytopenia undergoing percutaneous coronary intervention (PCI). Patients and MethodsWe performed a retrospective single-center study of patients with preprocedural thrombocytopenia (platelet count ≤100,000/μL; n=204) undergoing PCI between 2003 and 2015. Inhospital and late outcomes were compared with those of a matched control group without thrombocytopenia (n=1281). ResultsThe most common causes of thrombocytopenia were liver disease, immune-mediated disease, and hematologic malignant neoplasms. Inhospital bleeding events after PCI were similar in patients with thrombocytopenia and matched controls (24 of 146 [16.4%] vs 179 of 1281 [14.0%]; P=.40) and were largely classified as minor using the Bleeding Academic Research Consortium (BARC) classification (89% BARC 1 or 2). There was no significant difference in inhospital death (4 of 146 [2.7%] vs 71 of 1281 [2.0%]; P=.56), but patients with thrombocytopenia had higher rates of platelet and red blood cell transfusion (18 of 146 [12.3%] vs 93 of 1281 [7.2%]; P=.05). During long-term follow-up, Kaplan-Meier estimated rates of bleeding events (BARC ≥2) were higher for thrombocytopenia (at 5 years, 7.9% vs 3.6%; P=.03). Patients with thrombocytopenia had a similar risk of long-term cardiac mortality, but significantly higher rates of noncardiac mortality (at 5 years, 28% vs 21%; P=.02). ConclusionThis study suggests that short-term outcomes after PCI in patients with thrombocytopenia were favorable. On long-term follow-up, thrombocytopenia was associated with a higher risk of long-term noncardiac mortality and bleeding.

Validation of Three Platelet Function Tests for Bleeding Risk Stratification During Dual Antiplatelet Therapy Following Coronary Interventions.

Although low platelet reactivity (LPR) is commonly detected during bleeding, a validated threshold for reliable DAPT bleeding risk stratification is lacking. We tested the diagnostic utility of 3 conventional platelet-activity assays to define the predictive value (if any) of LPR for bleeding. We hypothesized whether one of these tests be better than any others for predicting bleeding events. Patients (n = 800) following drug-eluting stent implantation received DAPT. Bleeding was assessed by Bleeding Academic Research Consortium (BARC) classification and events were collected for 1 year after stenting. Platelet reactivity was measured by light transmittance aggregometry (LTA), VerifyNow, and multiple electrode aggregometry (MEA). The LPR values for bleeding event stratification were defined as ≤15% for LTA, ≤139 PRU for VerifyNow, and ≤25 U for MEA. Bleeding events occurred in 18 patients (2.3%). All tests distinguished LPR as an independent predictor for bleeding by univariate analysis ([HR]: 5.00, 95% [CI]: 1.8-14.0, P = 0.002 for LTA; HR: 21.3, 95% CI: 6.2-73.0, P < 0.0001 for VerifyNow; and HR: 7.4, 95% CI: 2.2-25.5, P = 0.002 for MEA). Multivariate analysis revealed that only VerifyNow (HR: 11.5, 95% CI: 2.9-45.7, P < 0.0004) remained an independent predictor for bleeding. However, the specificity (81.5%, 60.2%, and 81.7%, respectively) and sensitivity (61.1%, 83.3%, and 83.2%, respectively) of all 3 tests were quite low. Among 3 conventional platelet-activity assays, VerifyNow was better than LTA or MEA for triaging future bleeding risks. However, all 3 tests failed to reliably predict future bleeding.

Factores asociados a la presencia de sangrado clasificados por el Bleeding Academic Research Consortium, en pacientes con síndrome coronario agudo sometidos a intervención coronaria percutánea

Background and objectivesBleeding is the main non-cardiac complication related to percutaneous coronary intervention and it is associated to an increase of the risk of adverse events. Nowadays there are multiple scales to define risk of bleeding and several definitions for bleeding. The goal is to determine factors associated to the presence of bleeding in patients with acute coronary syndrome undergoing percutaneus coronary intervention, using the the Bleeding Academic Research Consortium scale to then issue recommendations. Material and methodsCase-control analytical observational study in patients with acute coronary syndrome undergoing percutaneous coronary intervention applying the Bleeding Academic Research Consortium scale. Cases were defined by patients who presented bleeding following the surgery (Bleeding Academic Research Consortium type 1-5) and controls by patients who did not show bleeding (Bleeding Academic Research Consortium type 0). Results366 were selected (121 cases, 245 controls). 33% of the patients showed some type of bleeding, divided into: type 1: 12%; type 2: 13.4%; type 3: 7.3% and type 5: 0.3%. Multivariate analysis of most important predictive factors for bleeding that were statistically significant were: female gender, warfarin treatment and use of Tirobifan during percutaneus coronary intervention. ConclusionsBleeding is a frequent event during percutaneus coronary intervention. According to the Bleeding Academic Research Consortium classification, most bleedings were of types 1 and 2. Risk factors for bleeding described worldwide are similar to those of this study. Female gender, warfarin treatment and use of Tirobifan were statistically significant. Bleeding Academic Research Consortium scale is considered a good indicator to define bleeding types.

One-year incidence and clinical impact of bleeding events in patients treated with prasugrel or clopidogrel after ST-segment elevation myocardial infarction

Little information is available on the long-term incidence of bleeding events after ST-segment elevation myocardial infarction (STEMI) with the current antithrombotic strategy. To evaluate the effect of bleedings for up to 12months on clinical events and therapeutic compliance in unselected STEMI patients treated with prasugrel or clopidogrel. Patients were treated with clopidogrel or prasugrel according to guidelines. The primary endpoint was first occurrence of a bleeding event from hospital discharge to 12months, assessed by the Bleeding Academic Research Consortium (BARC) classification using a dedicated questionnaire. Topography of bleedings, causes of premature cessation and ischaemic events were compared between clopidogrel- and prasugrel-treated patients. A total of 390patients were enrolled (211 in the prasugrel group, 179 in the clopidogrel group). Elderly, female and low-body weight patients were more likely to receive clopidogrel. At 12months, the incidence of major bleedings (BARC 3) was lower with prasugrel (1% vs 6%; P=0.02), mainly due to fewer transfusions. Elderly age was a risk factor for severe bleeding. Premature treatment cessation was related to ischaemic complications (P=0.03), and occurred more frequently with prasugrel (P=0.001). One-year mortality was very low (1.9 per 100person-years, 95% confidence interval 0.9-4.0), and was higher in the clopidogrel group (P=0.03). In this unselected STEMI population, the rate of major bleedings with prasugrel at 12months was low, but nuisance bleedings were frequent and led to more premature cessations than with clopidogrel. Prevention of bleeding complications, even minor, is necessary to prevent disruption of antithrombotic medication.

Influence of platelet reactivity on BARC classification in East Asian patients undergoing percutaneous coronary intervention. Results of the ACCEL-BLEED study.

An increasing body of data suggests that East Asian patients have differing risk profiles for both thrombophilia and bleeding compared with Western population. This study was designed to evaluate the relationship of bleeding to platelet function in East Asians undergoing percutaneous coronary intervention (PCI). Patients who had undergone uneventful PCI (n= 301) were prospectively enrolled and bleeding events were evaluated during dual antiplatelet therapy (DAPT) with aspirin and clopidogrel. Platelet function was measured during hospitalisation and at 30-day follow-up by light transmittance aggregometry (LTA) and vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) assay. During 30-day follow-up, 29.2 % of patients (n= 88) experienced post-discharge Bleeding Academic Research Consortium (BARC) complications (24.6 % and 7.0 % of BARC type 1 and 2, respectively). Patients presenting with acute myocardial infarction had fewer episodes of type 1 BARC bleeding (odds ratio: 0.41; 95 % confidence interval: 0.22 to 0.76; p= 0.005). The cut-off of low platelet reactivity (LPR) (20 µM ADP-induced platelet aggregation ≤ 46.1 %; platelet reactivity index ≤ 45.1 %) was the independent determinant of type 2 BARC bleeding (odds ratio: 3.55 and 4.44; p= 0.009 and 0.002, respectively). The first 30-day BARC bleeding episodes were associated with an increased rate of subsequent premature DAPT discontinuation during one-year follow-up (4.7 % vs 11.4 %; odds ratio: 2.60; 95 % confidence interval: 1.04 to 6.50; p= 0.035). In conclusion, among East Asians, mild bleeding episodes are common early after PCI and are associated with premature DAPT discontinuation. Type 2 BARC bleeding episodes are associated with LPR cut-offs measured at 30 days post-discharge.

Abstract 18394: Predicting Value of Platelet Reactivity on Bleeding and Major Adverse Cardiac Events in Eastern Asian PCI Patients

Introduction: Previous studies have shown that high and low platelet reactivity (HPR and LPR respectively) are associated with adverse events following percutaneous coronary intervention (PCI), however, therapy windows were not consistent in different studies. We aimed to determine the optimal cutoff value of platelet reactivity to prevent major adverse cardiac events (MACE) and bleeding in eastern Asian PCI patients. Methods: Consecutive 6266 non-emergent PCI patients with aspirin and clopidogrel therapy were enrolled prospectively in the single-center, large-volume investigation from January to December 2013. Platelet reactivity (ADP-induced platelet-fibrin clot strength [MAADP]) was determined by thrombelastography. MACE and Bleeding Academic Research Consortium (BARC) classification≥2 bleeding were assessed between different categories of platelet reactivity and Syntax Score (SS). Results: Overall, 475 MACE and 152 major bleeding (BARC grade≥2) events were recorded during one year follow-up. With receiver operating characteristic (ROC) curve, we determined the cutoff values of MAADP for MACE and major bleeding (45 mm and 34mm, respectively). Then, patients were classified according to MAADP (&gt;45 mm, 34-45 mm, and &lt;34 mm) and we evaluated the impact of platelet reactivity on MACE and major bleeding in different Syntax Score subgroups (SS45 mm was the predictor of MACE (HR: 2.3; 95%CI: 1.6-5.9), but MAADP45 mm was still the predictor of MACE (HR: 2.6; 95%CI: 1.3-6.3), while MAADP&lt;34 mm show significant impact on major bleeding (HR: 1.8; 95%CI: 1.2-4.7). Conclusions: Platelet reactivity measured by thrombelastography could predict MACE and major bleeding in elective PCI patients, especially in those with high SS. Therapy window of anti-platelet drugs is narrow in eastern Asian population and further studies on tailored treatment of high-risk patients are needed.

Racial and Ethnic Heterogeneity in Serum Lipid (SL) Prediction of Body Mass Index (BMI)

Whether nonintracranial hemorrhage (NICH) associated with intravenous thrombolysis (IVT) is a predictor of intracranial hemorrhage (ICH) and poor prognosis is ambiguous. We sought to analyze the rate of NICH and the relationship between NICH and poor outcome in the ischemic stroke population undergoing IVT.This is a single-center, hospital-based prospective study. All ischemic stroke patients undergoing IVT between December 2015 and November 2016 were included. NICH was defined according to the criteria of the Bleeding Academic Research Consortium (BARC). ICH associated with IVT was defined based on the European Cooperative Acute Stroke Study II definition. On the basis of the modified Rankin Scale (mRS), 90-day outcome was divided into favorable outcome (mRS score 0-1) versus unfavorable outcome (mRS score 2-6) and independency (mRS score 0-2) versus dependency and death (mRS score 3-6).A total of 212 patients undergoing IVT were included in the analysis. Forty-five NICH events were reported in 42 patients (19.8%). Older age was independently associated with NICH (P = .049, odds ratio [OR] = .97, 95% confidence interval [CI] .94-1.0). Neither NICH with BARC class 1 or higher (P = .56, OR = .61, 95% CI .11-3.24) nor NICH with BARC class 2 or higher (P = .87, OR = 1.19, 95% CI .14-10.23) was associated with ICH. NICH with BARC class 1 or higher was not associated with unfavorable outcome (P = .67, OR = 1.17, 95% CI .56-2.45) and dependence and death (P = .47, OR = .72, 95% CI .30-1.75), neither was NICH with BARC class 2 or higher (P = .97, OR = 1.02, 95% CI .46-2.27 and P = .30, OR = .59, 95% CI .22-1.62).NICH was common among ischemic stroke populations receiving IVT. NICH with BARC class 2 or lower was not associated with ICH and poor outcome.

Incremental Value of Platelet Reactivity Over a Risk Score of Clinical and Procedural Variables in Predicting Bleeding After Percutaneous Coronary Intervention via the Femoral Approach: Development and Validation of a New Bleeding Risk Score.

Growing evidence suggests that platelet reactivity (PR) may predict bleeding. We investigate the incremental value of PR in predicting bleeding after percutaneous coronary intervention (PCI) via the femoral approach over a validated bleeding risk score (BRS) of clinical and procedural variables. A total of 800 patients undergoing elective PCI via the femoral approach were included. PR was measured before PCI with the VerifyNow P2Y12 assay and low PR was defined as a P2Y12 reaction unit value ≤ 178. Calculation of the BRS included the following: age, sex, intra-aortic balloon pump, glycoprotein IIb/IIIa inhibitors, chronic kidney disease, anemia, and low-molecular-weight heparin within 48-hour pre-PCI. A new risk score including low PR (BRS-PR) was developed and validated in an independent cohort of patients (n = 310). Bleeding events at 30 days after PCI were defined according to the thrombolysis in myocardial infarction, Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE)-2, and Bleeding Academic Research Consortium criteria. Both BRS and PR showed high discriminatory power for bleeding (area under the curve [AUC] > 0.7 for all definitions). Discriminatory power of BRS-PR (AUC = 0.809 for thrombolysis in myocardial infarction bleeding; AUC = 0.814 for Bleeding Academic Research Consortium class ≥ 2 bleeding; AUC = 0.708 for Bleeding Academic Research Consortium class ≥ 3 bleeding; and AUC = 0.813 for REPLACE-2 bleeding) was significantly higher than that of BRS alone (P < 0.001 for all bleeding definitions). In the validation set, BRS-PR showed higher discriminatory power for thrombolysis in myocardial infarction bleeding than BRS alone (AUC = 0.788 versus 0.709; P = 0.036). PR has incremental predictive value on bleeding events after elective PCI via the femoral approach over a validated risk score of clinical and procedural variables. A risk score including PR yields significantly better prognostic performance compared with the original BRS.

Collagen plug-based vascular closure devices do not decrease vascular and bleeding complications occurring after balloon aortic valvuloplasty

The benefits of vascular closure devices (VCDs) in the prevention of vascular complications after femoral intervention remain controversial. To evaluate the efficiency of collagen plug-based VCDs in the prevention of femoral access complications after balloon aortic valvuloplasty. We conducted a prospective analysis of consecutive patients who underwent balloon aortic valvuloplasty by femoral retrograde technique in our centre between 2009 and 2012. Group 1 included 75 patients in whom femoral puncture haemostasis was obtained with the use of an 8F collagen plug-based VCD (Angio-Seal™; Saint-Jude Medical, Inc.); group 2 included 105 patients who had manual or mechanical groin compression (FemoStop™; RADI Medical Systems, Inc.). We did not use heparin during the procedure. We collected data on major in-hospital adverse events, majorbleeding (Bleeding Academic Research Consortium classification≥3) and vascular access complications. We included 180 patients with severe and symptomatic aortic stenosis. Indications for valvuloplasty were mainly bridge to transcatheter aortic valve implantation or palliative therapy (72%). The groups were similar in terms of median age, lower limb artery disease and body mass index. Vascular and bleeding complications occurred in 11.1% of patients and were not decreased with the use of VCDs (relative risk 2.60, 95% confidence interval 1.10-3.09; P=0.05). These findings were consistent across all prespecified subgroups. Duration of hospital stay was not reduced by VCDs. Based on the results of this study, performed with small-size sheaths and without heparin, collagen plug-based VCDs increase femoral access complications following aortic valvuloplasty. Systematic use of VCDs in elderly patients, with probable advanced limb atherosclerosis, is questionable.

Impact of clinical presentation on ischaemic and bleeding outcomes in patients receiving 6- or 24-month duration of dual-antiplatelet therapy after stent implantation: a pre-specified analysis from the PRODIGY (Prolonging Dual-Antiplatelet Treatment After Grading Stent-Induced Intimal Hyperplasia) trial

We investigated if acute coronary syndrome (ACS) rather than stable coronary artery disease (SCAD) presentation is an outcome modifier with respect to the duration of dual-antiplatelet therapy (DAPT) in patients undergoing coronary stenting. In the Prolonging Dual-Antiplatelet Treatment After Grading Stent-Induced Intimal Hyperplasia (PRODIGY) trial, a total of 1465 (74.3%) patients presented ACS whereas 505 (25.7%) had SCAD and were randomized to 6- or 24-month DAPT. At 24 months, the composite of death, myocardial infarction (MI), or cerebrovascular accident (CVA) did not differ between the long- and short-term DAPT arms in both ACS (11.1 vs. 11.7%; P = 0.67) and SCAD (7.5 vs. 4.8%; P = 0.21) patients, respectively. Long-term DAPT was associated with a 75% increase of Bleeding Academic Research Consortium (BARC)-class 2, 3, or 5 bleeding in ACS [7.1 vs. 4.1%; hazard ratio (HR) 1.75, 95% confidence interval (CI) 1.11-2.74, P = 0.015; number needed to treat for harm (NNTH): 33.3] and a five-fold increase in SCAD (8.2 vs. 1.6%; HR 5.37, 95% CI 1.84-15.74, P = 0.002; NNTH: 15.1) patients, with a borderline quantitative interaction (PINT = 0.056). As a result, net adverse cardiovascular events (death, MI, CVA, BARC class 2, 3, or 5 bleeding) were more than doubled in SCAD patients receiving 24-month DAPT, whereas they did not differ in ACS patients (PINT = 0.024). This analysis suggests that clinical presentation may be a treatment modifier with respect to DAPT duration after stenting consistent with the hypothesis that SCAD-but not ACS-patients are exposed to a significant increase in bleeding and net adverse clinical events when treated with 24-month compared with 6-month therapy. clinicaltrials.gov Identifier: NCT00611286. http://clinicaltrials.gov/ct2/show/NCT00611286?term=prodigy&rank=2.

Procedure-related bleeding in elective percutaneous coronary interventions.

Prognostic impact of procedure-related bleeding in patients with stable coronary artery disease (CAD) undergoing elective percutaneous coronary intervention (PCI) remains incompletely investigated. The aim of this study was to investigate the association between peri-PCI bleeding and 1-year outcome of patients with stable CAD. The study included 9035 patients with stable CAD who underwent elective PCI. Bleeding within 30 days of PCI was defined using the Bleeding Academic Research Consortium (BARC) criteria. The primary outcome was 1-year mortality. Bleeding occurred in 844 patients (9.3%). Actionable bleeding (BARC class ≥ 2) occurred in 442 patients (4.9%). There were 210 deaths (2.3%) at 1 year following PCI: 41 deaths among patients with bleeding and 169 deaths among patients without bleeding [Kaplan-Meier estimates of mortality, 4.9% and 2.1%; odds ratio = 2.41, 95% confidence interval (CI) 1.73-3.36, P < 0.001]. The association between bleeding and mortality remained significant after adjustment for baseline risk variables (adjusted hazard ratio = 1.87, 95% CI 1.27-2.76, P = 0.002). Bleeding increased the discriminatory power of the model regarding prediction of 1-year mortality (absolute and relative integrated discrimination improvement, 0.006% and 16.3%, respectively, P = 0.001). In patients with stable CAD undergoing elective PCI, the occurrence of bleeding within 30 days of the procedure was associated with increased risk of death at 1 year after PCI. These findings suggest that procedure-related bleeding may contribute to less than optimal results of PCI in terms of mortality reduction in patients with stable CAD.

0098: One year incidence and clinical impact of bleeding outcomes in STEMI patients treated by prasugrel or clopidogrel in real life: the BLEED-MI study

The aim of this study was to evaluate one-year incidence of bleeding events and their impact on compliance in patients admitted for ST Elevation Myocardial Infarction (STEMI) and treated by prasugrel or clopidogrel in « real-world ». Patients admitted for a STEMI were treated by either clopidogrel or prasugrel according to the physician with respect of guidelines. The primary endpoint was the first occurrence of bleeding events within 12 months assessed by the Bleeding Academic Research Consortium (BARC) classification using a dedicated questionnaire focused on bleeding events. Topography bleedings, causes of premature cessation and ischemic events were also compared. 390 patients were enrolled, 211 in prasugrel group and 179 in clopidogrel group. Patients in the prasugrel group were younger, with higher body weight and were more frequently men. At 12 months, a bleeding complication occurred in 40% of patients regardless of its severity or treatment prescribed. Major bleedings (BARC 3) were significantly lower with prasugrel than clopidogrel (1% versus 6%, p=0.001). Minimal bleedings (BARC 1) were more frequent in clopidogrel group than prasugrel group (respectively 27% and 18%; p=0.05). However BARC 2 bleedings occurred more often in prasugrel group (14% versus 6%, p=0.01) (figure). Subcutaneous and gastrointestinal haemorraghes were the most frequent. Over one-year, the rate of cessation was 18% in the prasugrel group and only 10% in the clopidogrel group (p=0.04). Respectively for prasugrel and clopidogrel, rates of recommend discontinuation were 10% and 4% (p=0.02) and of disruption were 8% and 5% (p=0.3). Despite more frequent discontinuation, mortality remains very low in the prasugrel group (0.5% versus 7%, p=0.0003). In real-world, in a low bleeding risk population, the rate of major bleedings with prasugrel at 12 months was low but nuisance bleedings were frequent with significant impact on premature cessation Abstract 0098 – Figure: 12 months bleedings classification

Impact of in‐hospital bleeding according to the bleeding academic research consortium classification on the long‐term adverse outcomes in patients undergoing percutaneous coronary intervention

The aim of this study was to assess the impact of bleeding after percutaneous coronary intervention (PCI) with drug-eluting stents on long-term clinical events according to the newly proposed Bleeding Academic Research Consortium (BARC) classification. Current evidence about the impact of the BARC classification is limited. Out of a total of 6,166 patients who underwent PCI in a prospective IRIS-DES registry, the impact of in-hospital bleeding defined as the BARC classification on major adverse cardiovascular events (MACE) comprising death, myocardial infarction (MI), or stroke was analyzed. In-hospital bleeding occurred in 235 patients (3.8%) according to BARC classification. During the 2-year follow-up, MACE occurred in 599 patients (9.7%). The 2-year incidence of MACE was significantly higher in patients with bleeding (16.7% vs. 8.3%; adjusted hazard ratio [HR], 1.6; 95% confidence interval [CI], 1.2-2.3; P = 0.002) than in those without bleeding. We observed a higher risk of MI (12.4% vs. 6.4%; adjusted HR, 1.7; 95% CI, 1.2-2.6, P = 0.005), stroke (3.0% vs. 0.6%; adjusted HR, 2.9; 95% CI, 1.4-6.2, P = 0.005) in patients with bleeding. Death (3.8% vs. 1.6%; adjusted HR, 1.6; 95% CI, 0.9-3.0, P = 0.120) and target vessel revascularization (4.3% vs. 1.9%; adjusted HR, 1.6; 95% CI, 0.9-2.9, P = 0.108) were statistically insignificant. Incidence, adjusted HR and P-value were similar between BARC and TIMI classification. In-hospital bleeding events according to the newly proposed BARC definition were significantly associated with an increased risk of adverse long-term events in patients undergoing PCI with drug-eluting stents. © 2014 Wiley Periodicals, Inc.

The Prognostic Value of Bleeding Academic Research Consortium (BARC)-Defined Bleeding Complications in ST-Segment Elevation Myocardial Infarction: A Comparison With the TIMI (Thrombolysis In Myocardial Infarction), GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries), and ISTH (International Society on Thrombosis and Haemostasis) Bleeding Classifications

The aim of the present analysis was to compare 1-year mortality prediction of Bleeding Academic Research Consortium (BARC)-defined bleeding complications with existing bleeding definitions in patients with ST-segment elevation myocardial infarction (STEMI) and to investigate the prognostic value of the individual data elements ofthebleeding classifications for 1-year mortality. BARC recently proposed a novel standardized bleeding definition. The in-hospital occurrence of bleeding defined according to the BARC, TIMI (Thrombolysis In Myocardial Infarction), GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries), andISTH (International Society on Thrombosis and Haemostasis) bleeding classifications was assessed in 2,002 STEMI patients undergoing primary percutaneous coronary intervention between January 1, 2003, and July 31,2008. BARC types 2, 3, 4, and 5 bleeding occurred in 4.4%, 14.2%, 1.4%, and 0.3% of patients, respectively. By multivariable analysis, GUSTO- and ISTH-defined bleeding was not significantly associated with 1-year mortality, whereas TIMI major and BARC type 3b or 3c bleeding conferred a 2-fold higher risk of 1-year mortality (hazard ratios[HRs]: 2.00 [95% confidence interval (CI): 1.32 to 3.01] and 1.84 [95% CI: 1.23 to 2.77], respectively). Data elements most strongly associated with mortality were a hemoglobin decrease≥5 g/dl (HR: 1.94 [95% CI: 1.26 to 2.98]), the use of vasoactive agents for bleeding (HR: 2.01 [95% CI: 0.91 to 4.44]), cardiac tamponade (HR: 2.38 [95% CI: 0.56 to 10.1]), and intracranial hemorrhage (HRs for 1-year mortality were not computable because there was only 1 patient with intracranial bleeding). Both the BARC and TIMI bleeding classification identified STEMI patients at risk of 1-year mortality.