Bleeding Academic Research Consortium Definition Research Articles

Incidence, Source, Determinants, And Prognostic Impact Of Major Bleeding In Outpatients With Chronic Heart Failure: Insights From The CARDIONOR Registry

Risk, correlates, and consequences of major bleeding as well as the frequency of antithrombotic use in heart failure (HF) patients are largely unknown. We analyzed incident major bleeding during a 3-year follow-up in 2910 HF outpatients included in the prospective multicenter CARDIONOR registry. Major bleeding was defined as a type ≥ 3 bleed using the Bleeding Academic Research Consortium (BARC) definition and adjudicated by a blinded committee. Most patients were male (62%) with a mean age of 71.6 ± 12.8 years. The mean LVEF was 48 ± 13% with proportions being 50% for preserved, 24% for mid-range, and 26% for reduced LVEF. Altogether, 45% of the patients had a history of CAD. The NYHA class was ≥ 3 in 22.8% of the cases. There was a high prevalence of AF at inclusion (57.3%). At inclusion, most patients (89%) received at least one antithrombotic: anticoagulation (54%) and/or antiplatelet therapy (46%). Major bleeding occurred in 111 patients (3-year cumulative incidence: 3.6% [95%CI: 3.0-4.3]). Most events were BARC 3a (32.5%) or 3b (31.5%). Most frequent sites of bleeding were gastrointestinal (40.6%) and intracranial (27.9%). Anticoagulation was used in 82% of the patients at time of major bleeding. Variables associated with major bleeding were atrial fibrillation (P < 0.0001), diabetes (P = 0.012), and older age (P = 0.049). The incidence of bleeding was similar in HF patients with preserved, mid-range or reduced left ventricle ejection fraction (LVEF), with mild or severe HF symptoms, and with ischemic or non-ischemic HF. Major bleeding was strongly associated with mortality (adjusted hazard ratio: 5.63; 95% CI 4.37–7.24; P < 0.0001). In HF outpatients, major bleeding occurs at a stable rate of 1.2% annually and is associated with a dramatic increase in mortality. Most events occur in patients receiving anticoagulation. The risk of bleeding is similar in patients with preserved, mid-range, or reduced LVEF.

Relative impact of bleedings over ischaemic events in patients with heart failure: insights from the CARDIONOR registry.

AimsMajor bleeding events in heart failure (HF) patients are poorly described. We sought to investigate the importance of major bleeding and its impact on outcomes in HF patients.Methods and resultsWe analysed incident bleeding and ischaemic events during a 3 year follow‐up in 2910 HF outpatients included in a prospective multicentre registry. Major bleeding was defined as a Type ≥3 bleed using the Bleeding Academic Research Consortium definition. Ischaemic event was a composite of ischaemic stroke and myocardial infarction. Events were adjudicated by a blinded committee. At inclusion, most patients (89%) received at least one antithrombotic: anticoagulation (53.9%) and/or antiplatelet therapy (46.2%). Bleeding occurred in 111 patients {3 year cumulative incidence: 3.6% [95% confidence interval (CI) 3.0–4.3]} and ischaemic events in 102 patients [3 year cumulative incidence: 3.3% (95% CI 2.7–4.0)]. Most bleedings were Bleeding Academic Research Consortium 3a (32.5%) or 3b (31.5%). Most frequent sites of bleeding were gastrointestinal (40.6%) and intracranial (27.9%). Variables associated with bleeding were atrial fibrillation [hazard ratio (HR) = 2.63 (95% CI 1.66–4.19), P < 0.0001], diabetes [HR = 1.62 (95% CI 1.11–2.38), P = 0.012], and older age [HR = 1.19 per 10 year increase (95% CI 1.00–1.41), P = 0.049]. Anticoagulation use was associated with a two‐fold increase in the bleeding risk. Bleeding events as well as ischaemic events were strongly associated with subsequent mortality [adjusted HRs: 5.67 (4.41–7.29), P < 0.0001 and 4.29 (3.18–5.78), P < 0.0001, respectively].ConclusionsIn HF outpatients, antithrombotics are widely used. Bleeding occurs at a stable rate of 1.2% annually (as frequent as ischaemic events) and is associated with a dramatic increase in mortality (at least as severe as ischaemic events). Most events occurred in patients receiving anticoagulation. Knowledge of these findings may help physicians to manage antithrombotics in HF patients.

1-Year COMBO stent outcomes stratified by the PARIS bleeding prediction score: From the MASCOT registry.

BackgroundThe COMBO stent is a biodegradable-polymer sirolimus-eluting stent with endothelial progenitor cell capture technology for faster endothelialization.ObjectiveWe analyzed COMBO stent outcomes in relation to bleeding risk using the PARIS bleeding score.MethodsMASCOT was an international registry of all-comers undergoing attempted COMBO stent implantation. We stratified patients as low bleeding-risk (LBR) for PARIS score ≤ 3 and intermediate-to-high (IHBR) for score > 3 based on baseline age, body mass index, anemia, current smoking, chronic kidney disease and need for triple therapy. Primary endpoint was 1-year target lesion failure (TLF), composite of cardiac death, myocardial infarction (MI) not clearly attributed to a non-target vessel or clinically-driven target lesion revascularization (TLR). Bleeding was adjudicated using the Bleeding Academic Research Consortium (BARC) definition. Dual antiplatelet therapy (DAPT) cessation was independently adjudicated.ResultsThe study included 56% (n = 1270) LBR and 44% (n = 1009) IHBR patients. Incidence of 1-year TLF was higher in IHBR patients (4.1% vs. 2.6%, p = 0.047) driven by cardiac death (1.7% vs. 0.7%, p = 0.029) with similar rates of MI (1.8% vs. 1.1%, p = 0.17), TLR (1.5% vs. 1.6%, p = 0.89) and definite/ probable stent thrombosis (1.2% vs. 0.6%, p = 0.16). Incidence of 1-year major BARC 3 or 5 bleeding was significantly higher in IHBR patients (2.3% vs. 0.9%, p = 0.0094), as was the incidence of DAPT cessation (29.3% vs. 22.8%, p < 0.01), driven by physician-guided discontinuation.ConclusionsPatients with intermediate-to-high PARIS bleeding risk in the MASCOT registry experienced greater incidence of 1-year TLF, major bleeding and DAPT cessation than LBR patients, without significant differences in stent thrombosis.

Assessing bleeding in acute coronary syndrome using the Bleeding Academic Research Consortium definition

The Bleeding Academic Research Consortium (BARC) definition was proposed to overcome the heterogeneity among the many bleeding definitions. The aim of this study-level meta-analysis was to explore the incidence of BARC-assessed bleeding in acute coronary syndrome (ACS) studies and to ascertain the relation between these events and variables related to bleeding risk. We searched the literature for studies that reported bleeding events according to BARC criteria in ACS patients. An analysis on heterogeneity between studies in bleeding reports was performed with I test. A meta-regression was conducted to explore the relation between different types of BARC bleedings and patient and procedural features. Nine studies were included in the analysis. Overall, BARC 2 rates were higher than BARC 3 or 5 rates (6.3 versus 2.6%). An extremely high level of heterogeneity was detected both for BARC 2 (I 99.3%) and BARC 3 or 5 (I 97.5%) bleedings. Increasing age [β coefficient 0.4% (0.2-0.6%); P < 0.001] and renal impairment [β coefficient 1 6.5% (1-32.1%); P = 0.037] were associated with increased BARC 3 or 5 rates, whereas the use of glycoprotein IIb/IIIa inhibitors was the only factor related to an increased incidence of BARC 2 bleeding [β coefficient 2 2.3% (5.5-39%); P = 0.009]. The high level of heterogeneity in BARC bleeding reports only partially explained by bleeding risk profile suggests that a regulatory guidance to properly evaluate bleedings and to estimate the risk--benefit in clinical trials investigating different antithrombotic treatments in ACS patients is needed.

Personalized antiplatelet therapy guided by a novel detection of platelet aggregation function in stable coronary artery disease patients undergoing percutaneous coronary intervention: a randomized controlled clinical trial.

A number of studies have attempted to demonstrate the benefits associated with personalized antiplatelet therapy guided by platelet function testing, which has led to disappointing findings. In this study, we used a new platelet function test to guide antiplatelet therapy in stable coronary artery disease (CAD) patients after percutaneous coronary intervention (PCI). In the present randomized controlled trial, a total of 2237 patients with stable CAD undergoing PCI were randomly chosen to be administered personalized antiplatelet therapy (personalized group; n = 1123) or standard antiplatelet treatment (standard group; n = 1114). The patients in the standard therapy group, without detecting the platelet aggregation rate, were administered a 75 mg/day clopidogrel maintenance dosage plus 100 mg/day of aspirin for at least 6 months after the procedure. For the patients in the personalized therapy group, the antiplatelet strategy was performed according to the maximum aggregation rate (MAR), determined using a novel platelet analyser, PL-12. If MAR > 55%, 90 mg ticagrelor was administered twice daily plus 100 mg/day of aspirin after PCI. If MAR ≤55%, 75 mg/day clopidogrel plus 100 mg/day of aspirin was administered after PCI. The primary endpoint was net clinical adverse events, which were a composite of cardiac death, myocardial infarction, stroke, stent thrombosis, urgent revascularization, and bleeding [Bleeding Academic Research Consortium (BARC) definitions, Type 2, 3, or 5], in the 180-day period after randomization. The primary endpoint was reached in 58 patients in the personalized group, compared with 85 patients in the standard group [5.1% vs. 7.5%, hazard ratio (HR) 0.678, 95% confidence interval (CI) 0.486-0.947, P = 0.023], on intention-to-treat analysis. We also found that the net clinical adverse events (including ischaemic and bleeding events) were significantly reduced in the personalized group at 30 days after PCI compared to the standard group (1.5% vs. 3.0%, HR 0.510, 95% CI 0.284-0.915, P = 0.020). We did not find a significant difference in major bleeding events at either the 30-day (0.5% vs. 0.3%, P = 0.322) or the 180-day follow-up (2.1% vs. 1.6%, P = 0.364) between the two groups. The present study suggests that personalized antiplatelet therapy according to MAR can significantly improve the net clinical benefit 180 days after PCI.

P1843Transcatheter aortic valve implantation in patients with uninterrupted vitamin k antagonist

Abstract Background Bridging of vitamin K antagonist (VKA) with heparin is usually not promoted during interventional or surgical procedures related to increased risk of bleeding and thrombotic events but this strategy has not been evaluated during TAVI. Purpose The aim of this study was to evaluate the rate of major bleeding and vascular complications after TAVI performed in patients with uninterrupted VKA. Methods From January 2016 to October 2017, consecutive patients who underwent TAVI with uninterrupted VKA (INR between 1.5 and 3.5) were prospectively included in a monocentric registry. TAVI were performed according to current guidelines and a 50UI/kg bolus of heparin was injected at the beginning of the procedure for all patients. Vascular and bleeding complications were assessed using the Valve Academic Research Consortium 2 (VARC2) and the Bleeding Academic Research Consortium (BARC) definitions at 30 day follow-up. Results A total of 88 patients were included with a median age of 84 years [81.8–87], 42% being female, the median STS score was 5.1 [4.1–7.5], the median CHADS2-VASc was 5.5 [5–6] and 60.2% had a chronic kidney failure. Median INR at time of implantation was at 2.1 [1.8–2.6]. VKA were used for atrial fibrillation (89.8%), mechanic mitral prosthesis (5.7%) or venous thromboembolic disease (4.5%). Trans femoral access was used in 88.6% of the patients. Major bleeding (BARC ≥3b) occurred in 5 patients (5,7%) and major vascular complications occurred in 7 patients (8%). Peripheral arterial disease (RR = 10.95; 95% CI: 1.63 to 73.75; p=0.014) and carotid access (RR=8.56; 95% CI: 1.19 to 61.51; p=0.033) were significantly associated with major bleeding. INR &gt;2.5 was significantly associated with vascular complications (RR=7.14; 95% CI: 1.29 to 39.63; p=0.025). In multivariate analysis, Body mass index (OR=1.26; 95% CI: 1.02 to 1.57; p=0.032) and INR &gt;2.5 (OR=18.91; 95% CI: 1.62 to 221.26; p=0.010) were independent factor significantly associated with vascular complications or major bleeding. Mortality rate at 30 days follow-up was 2.3%, there was no myocardial infarction and stroke rate was 4.5%. Figure 1. Study flowchart Conclusion TAVI with uninterrupted VKA treatment seems to be feasible and safe with low risk of bleeding and vascular complications in this first single centre experience. Particular caution is advocated in low BMI patients and to keep INR&lt;2.5.

Association of Parenteral Anticoagulation Therapy With Outcomes in Chinese Patients Undergoing Percutaneous Coronary Intervention for Non–ST-Segment Elevation Acute Coronary Syndrome

The association of parenteral anticoagulation therapy with improved outcomes in patients with non-ST-segment elevation acute coronary syndrome was previously established. This benefit has not been evaluated in the era of dual antiplatelet therapy and percutaneous coronary intervention. To evaluate the association between parenteral anticoagulation therapy and clinical outcomes in patients with non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention. This cohort study included 8197 adults who underwent percutaneous coronary intervention for non-ST-segment elevation acute coronary syndrome from January 1, 2010, to December 31, 2014, at 5 medical centers in China. Patients receiving parenteral anticoagulation therapy only after percutaneous coronary intervention were excluded. Parenteral anticoagulation therapy. The primary outcome was in-hospital all-cause death and in-hospital major bleeding as defined by the Bleeding Academic Research Consortium definition (grades 3-5). Of 6804 patients who met the final criteria, 5104 (75.0%) were male, with a mean (SD) age of 64.2 (10.4) years. The incidence of in-hospital death was not significantly different between the patients who received and did not receive parenteral anticoagulation therapy (0.3% vs 0.1%; P = .13) (adjusted odds ratio, 1.27; 95% CI, 0.38-4.27; P = .70). A similar result was found for myocardial infarction (0.3% vs 0.3%; P = .82) (adjusted odds ratio, 0.77; 95% CI, 0.29-2.07; P = .61). In-hospital major bleeding was more frequent in the parenteral anticoagulation group (2.5% vs 1.0%; P < .001) (adjusted odds ratio, 1.94; 95% CI, 1.24-3.03; P = .004). At a median (interquartile range) follow-up of 2.96 years (1.93-4.46 years), all-cause death was not significantly different between the 2 groups (adjusted hazards ratio, 0.87; 95% CI, 0.71-1.07; P = .19), but the incidence of major bleeding was higher in the parenteral anticoagulation group (adjusted hazards ratio, 1.43; 95% CI, 1.01-2.02; P = .04). The propensity score analysis confirmed these primary analyses. In the patients undergoing percutaneous coronary intervention for non-ST-segment elevation acute coronary syndrome, parenteral anticoagulation therapy was not associated with a lower risk of all-cause death or myocardial infarction but was significantly associated with a higher risk of major bleeding. These findings raise important safety questions about the current practice of routine parenteral anticoagulation therapy while we await randomized trials of this practice.

Evaluation of Definitions for Oral Anticoagulant–Associated Major Bleeding: A Population-Based Cohort Study

Background: Major bleeding is the most serious complication of oral anticoagulation. Consensus criteria to define major bleeding have been established by the International Society for Thrombosis and Haemostasis (ISTH), Bleeding Academic Research Consortium (BARC) and Thrombolysis in Myocardial Infarction (TIMI). Significant variability exists across these definitions, and their agreement for identifying oral anticoagulant (OAC) related major bleeding is unknown. Furthermore, the association between each definition and mortality in cases of OAC bleeding has not been evaluated. We therefore, sought to evaluate the agreement of cases identified as major bleeding by the ISTH, BARC and TIMI definitions, and to assess associated in-hospital (emergency department or inpatient) and 30-day mortality of cases identified by these criteria.Methods: We used an existing dataset of individuals ≥66 years in Ontario, Canada, who presented to one of five tertiary care institutions with OAC related bleeding across three cities from 2010-2015. Detailed clinical data on consecutive episodes of OAC-associated bleeding were linked to population-based databases held at the Institute for Clinical Evaluative Sciences. We calculated Cohen's κ for agreement between the three major bleeding definitions, and used Pearson's χ2 to determine any differences in in-hospital and 30-day mortality for cases defined as major bleeding by ISTH, BARC and TIMI criteria.Results: We included 2,002 cases of OAC related bleeding in the analysis (460 on direct oral anticoagulants, 1,542 on warfarin). ISTH, BARC and TIMI major bleeding definitions were met in 75%, 77% and 29% of cases, respectively. 18% of cases did not meet criteria for major bleeding by any definition. Age, sex, CHA2DS2-VASc and HAS-BLED score, as well as proportion of chronic kidney disease were similar across ISTH-, BARC- and TIMI-defined cases. Over 9 in 10 cases of TIMI-defined major bleeding events involved an intracranial hemorrhage (94.4%), compared to 37% and 36% of cases identified by ISTH or BARC definitions respectively (p<0.001 across three groups). Agreement in case identification between ISTH and BARC was substantial (agreement 89%; Cohen's κ=0.69). On the other hand, agreement between TIMI and both ISTH (agreement 54%; Cohen's κ =0.24) and BARC (agreement 52%; Cohen's κ=0.21) were poor. The association between in-hospital mortality and TIMI-defined major bleeding was higher (29%) than that for ISTH and BARC (17% for both; p<0.001 for TIMI vs. ISTH and TIMI vs. BARC). The association with 30-day mortality showed a similar trend (30%, 18% and 18% for TIMI-, ISTH- and BARC- defined major bleeding events respectively; p<0.001 for TIMI vs. ISTH and TIMI vs. BARC). 6% of cases that were not categorized as major bleeding by ISTH or BARC definitions died within 30 days of hospital presentation, and this was 10% for cases not meeting criteria for TIMI major bleeding (10%, p=0.036 by Pearson's χ2).Conclusions: Among patients with OAC-associated bleeding, major bleeding events identified by ISTH and BARC criteria showed good agreement and similar prognostic utility. Meanwhile, TIMI criteria identified patients with higher clinical risk and subsequent mortality. Patients presenting with OAC-associated bleeding who did not fulfill ISTH or BARC major bleeding criteria had considerable risk of 30-day mortality and was even higher among those not meeting the TIMI criteria. Our findings suggest the need to refine current major bleeding definitions to identify additional patients at risk of death. DisclosuresWells:Bayer: Honoraria; BMS: Honoraria, Research Funding; Sanofi: Honoraria; Janssen: Honoraria. Sholzberg:Amgen: Research Funding; CSL Behring: Research Funding; Octapharma: Research Funding; Shire: Research Funding.

Evaluation of the Patterns of Non-Adherence to Anti-Platelet Regimens in Stented Patients Bleeding Score for Predicting the Long-term Out-of-hospital Bleeding Risk in Chinese Patients after Percutaneous Coronary Intervention.

Background:The Patterns of Non-Adherence to Anti-Platelet Regimens in Stented Patients (PARIS) bleeding score is a novel score for predicting the out-of-hospital bleeding risk after percutaneous coronary intervention (PCI). However, whether this score has the same value in non-European and American populations is unclear. This study aimed to assess the PARIS bleeding score's predictive value of bleeding in patients after PCI in the Chinese population.Methods:We performed a prospective, observational study of 10,724 patients who underwent PCI from January to December 2013, in Fuwai Hospital, China. We defined the primary end point as major bleeding (MB) according to Bleeding Academic Research Consortium definition criteria including Type 2, 3, or 5. The predictive value of the PARIS bleeding score was assessed with the area under the receiver operating characteristic (AUROC) curve.Results:Of 9782 patients, 245 (2.50%) MB events occurred during the 2 years of follow-up. The PARIS bleeding score was significantly higher in the MB group than that of non-MB group (4.00 [3.00, 5.00] vs. 3.00 [2.00, 5.00], Z = 3.71, P < 0.001). According to risk stratification of the PARIS bleeding score, the bleeding risk in the intermediate- and high-risk groups was 1.50 times (hazard ratio [HR]: 1.50; 95% confidence interval [CI]: 1.160–1.950; P = 0.002) and 2.27 times higher (HR: 2.27; 95% CI: 1.320–3.900; P = 0.003) than that in the low-risk group. The PARIS bleeding score showed a moderate predictive value for MB in the overall population (AUROC: 0.568, 95% CI: 0.532–0.605; P < 0.001) and acute coronary syndrome (ACS) subgroup (AUROC: 0.578, 95% CI: 0.530–0.626; P = 0.001) and tended to be predictive in the non-ACS subgroup (AUROC: 0.556, 95% CI: 0.501–0.611; P = 0.054).Conclusion:The PARIS bleeding score shows good clinical value for risk stratification and has a significant, but relatively limited, prognostic value for out-of-hospital bleeding in the Chinese population after PCI.

Association of Plasma Lipoprotein(a) With Long-Term Adverse Events in Patients With Chronic Kidney Disease Who Underwent Percutaneous Coronary Intervention

We aimed to determine the association of plasma lipoprotein(a) (Lp[a]) with long-term clinical outcomes in patients with chronic kidney disease (CKD) after percutaneous coronary intervention (PCI) in an observational cohort study. Four hundred and twenty-seven consecutive patients with CKD who underwent PCI from January 2013 to December 2013 were included in this study. Patients were divided into 2 groups according to median levels of Lp(a). Outcomes included 2-year risk of major adverse cardiovascular and cerebrovascular events (MACCEs) and bleeding according to Bleeding Academic Research Consortium definitions. Overall, median of Lp(a) in all the patients was 217.8 mg/L. The 2-year MACCE rate across the high Lp(a) and low Lp(a) group was 23.0% versus 15.4% (p = 0.047) and bleeding event rate of the two groups 8.9% versus 4.2% (p = 0.049). The Lp(a) was significantly and positively correlated with high-sensitivity C-reactive protein levels (r2 = 0.03, p < 0.001). Kaplan-Meier curves revealed that high Lp(a) had higher incidence of bleeding than low Lp(a) (p = 0.043) and had higher risk of MACCE (p = 0.049). Multivariable Cox regression analysis indicated that high Lp(a) was an independent predictor of Bleeding Academic Research Consortium bleeding compared with low Lp(a) (hazard ratios 2.29, 95% confidence intervals 1.01 to 5.15, p = 0.046). In conclusion, a high Lp(a) value may be associated with a poor prognosis after PCI for patients with CKD.

Sex-based differences in bleeding and long-term adverse events after percutaneous coronary intervention in older patients with coronary artery disease.

Differences in outcomes for women and men after percutaneous coronary intervention (PCI) in older patients remain controversial. Herein, we compared 2-year outcomes by sex in Chinese older patients undergoing PCI. A total of 4926 consecutive patients (33.6% women, age ≥60 years, mean age 67.4 ± 5.7 years) who underwent PCI at a single center in China from January 2013 to December 2013 were included in this study. The primary endpoint was 2-year risk of bleeding according to the Bleeding Academic Research Consortium definitions. The secondary endpoints included 2-year risk of major adverse cardiovascular and cerebrovascular events (MACCE). Hazard ratios were generated using multivariable Cox regression. Compared with men, women had significantly higher rates of in-hospital all-cause mortality (0.8% vs 0.2%, P = 0.001), cardiac death (0.5% vs 0.1%, P = 0.006), MACCE (2.4% vs 1.5%, P = 0.017), and bleeding (0.4% vs 0.1%, P = 0.015). At 2-year follow up, there were no differences between men and women for all-cause mortality (1.9% vs 1.8%, P = 0.839) and 2-year MACCE (13.1% vs 11.8%, P = 0.216). However, women had a higher risk of 2-year bleeding (9.2% vs 6.2%, P < 0.001), which persisted after adjusting for baseline differences and treatment characteristics (hazard ratio 1.35, 95% confidence interval 1.06-1.71; P = 0.014). We found that older women undergoing PCI were at increased risk of 2-year bleeding compared with men. Further dedicated studies are needed to confirm these findings.

Evaluation of CRUSADE and ACUITY-HORIZONS Scores for Predicting Long-term Out-of-Hospital Bleeding after Percutaneous Coronary Interventions.

Background:There is scanty evidence concerning the ability of Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the ACC/AHA Guidelines (CRUSADE) and Acute Catheterization and Urgent Intervention Triage Strategy and Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (ACUITY-HORIZONS) scores to predict out-of-hospital bleeding risk after percutaneous coronary interventions (PCIs) with drug-eluting stents (DES) in patients receiving dual antiplatelet therapy. We aimed to assess and compare the long-term prognostic value of these scores regarding out-of-hospital bleeding risk in such patients.Methods:We performed a prospective observational study of 10,724 patients undergoing PCI between January and December 2013 in Fuwai Hospital, China. All patients were followed up for 2 years and evaluated through the Fuwai Hospital Follow-up Center. Major bleeding was defined as Types 2, 3, and 5 according to Bleeding Academic Research Consortium Definition criteria.Results:During a 2-year follow-up, 245 of 9782 patients (2.5%) had major bleeding (MB). CRUSADE (21.00 [12.00, 29.75] vs. 18.00 [11.00, 26.00], P < 0.001) and ACUITY-HORIZONS (9.00 [3.00, 14.00] vs. 6.00 [3.00, 12.00], P < 0.001) risk scores were both significantly higher in the MB than non-MB groups. Both scores showed a moderate predictive value for MB in the whole study cohort (area under the receiver-operating characteristics curve [AUROC], 0.565; 95% confidence interval [CI], 0.529–0.601, P = 0.001; AUROC, 0.566; 95% CI, 0.529–0.603, P < 0.001, respectively) and in the acute coronary syndrome (ACS) subgroup (AUROC: 0.579, 95% CI: 0.531–0.627, P = 0.001; AUROC, 0.591; 95% CI, 0.544–0.638, P < 0.001, respectively). However, neither score was a significant predictor in the non-ACS subgroup (P > 0.05). The value of CRUSADE and ACUITY-HORIZONS scores did not differ significantly (P > 0.05) in the whole cohort, ACS subgroup, or non-ACS subgroup.Conclusions:CRUSADE and ACUITY-HORIZONS scores showed statistically significant but relatively limited long-term prognostic value for out-of-hospital MB after PCI with DES in a cohort of Chinese patients. The value of CRUSADE and ACUITY-HORIZONS scores did not differ significantly (P > 0.05) in the whole cohort, ACS subgroup, or non-ACS subgroup.

Antiplatelet treatment in diabetic patients with acute coronary syndrome undergoing percutaneous coronary intervention: a GReek AntiPlatElet registry substudy.

We compared the clinical outcome of diabetic versus nondiabetic patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) in the GReek AntiPlatElet (GRAPE) registry. GRAPE is a prospective observational study, focusing on contemporary antiplatelet use in moderate-risk to high-risk ACS patients receiving PCI. Major adverse cardiovascular events (MACE), (composite of death, nonfatal myocardial infarction, urgent revascularization, and stroke) and bleeding events (Bleeding Academic Research Consortium definition) at 1 year of follow-up were analyzed using propensity score adjustment. A subanalysis according to diabetes mellitus (DM) status was performed. Out of 2047 registered patients, 469 (22.9%) were diabetic. Complete 1-year follow-up was available in 95.1% of patients. MACE occurred in 12.2 and 7.2% of those patients with and without DM, respectively [adjusted hazard ratio (HR), 95% confidence interval (CI)=1.27 (0.89-1.79), P=0.2]. Observed BARC type ≥3 bleeding risk was not higher in diabetic patients: adjusted HR (95% CI)=1.20 (0.79-1.84). In the subgroup of clopidogrel-treated patients (N=238), MACE rate was significantly higher in diabetic compared with nondiabetic cohort [13.4 vs. 9%, adjusted HR (95% CI)=1.68 (1.07-2.64), P=0.03]. In the subgroup of ticagrelor-treated or prasugrel-treated patients (N=228), MACE rate did not differ significantly between diabetic and nondiabetic patients: 9.6 versus 5%, adjusted HR (95% CI)=1.35 (0.77-2.37), P=0.38. In 'real-life' ACS undergoing PCI, diabetic patients have higher - although not significantly - MACE rate and no difference in bleeding events. This difference in MACE was significant among clopidogrel-treated patients, whereas when newer antiplatelet agents were used the negative impact of DM on ischemic events was eliminated.

Head-to-head comparison of prasugrel versus ticagrelor in patients undergoing percutaneous coronary intervention: A meta-analysis of randomized controlled trials.

We sought to compare the efficacy and safety of prasugrel and ticagrelor in patients with coronary artery disease undergoing percutaneous coronary intervention (PCI). Evidence from randomized head-to-head comparison between prasugrel and ticagrelor is rare regarding clinical endpoints. PubMed, the Cochrane Library, and Web of Science were queried with the terms "prasugrel," "ticagrelor," and "randomized." Relevant randomized controlled trials (RCTs) or the same terms were also surveyed using clinicaltrials.gov, escardio.org, pcronline.org, and tctmd.com. The clinical endpoints were death, myocardial infarction (MI), stroke, and stent thrombosis (ST) for efficacy, and any bleeding for safety. A total number of 2068 patients in 12 RCTs, whose longest follow-up period was 6 months, was included in this study. The risks of death (odds ratio [OR]: 0.86, 95% confidence interval [CI]: 0.46-1.62, P = 0.647), MI (OR: 1.61, 95%CI: 0.71-3.62, P = 0.252), stroke (OR: 1.45, 95%CI: 0.25-8.36, P = 0.680), and ST (OR: 0.76, 95%CI: 0.20-2.81, P = 0.677) were similar between prasugrel and ticagrelor, respectively. While the incidence of bleeding according to the Bleeding Academic Research Consortium definitions was also comparable (OR: 0.83, 95%CI: 0.45-1.52, P = 0.539), that according to the Thrombolysis in Myocardial Infarction criteria was lower in prasugrel than ticagrelor (OR: 0.49, 95%CI: 0.24-0.97, P = 0.042). Although the efficacy was similar between prasugrel and ticagrelor, prasugrel may be associated with a lower risk of bleeding compared with ticagrelor during short- to mid-term follow-up period after PCI. Further studies are warranted in a larger patient population during longer-term follow up to validate these findings.

Use of the Dual-Antiplatelet Therapy Score to Guide Treatment Duration After Percutaneous Coronary Intervention.

The dual-antiplatelet therapy (DAPT) score was developed to identify patients more likely to derive harm (score <2) or benefit (score ≥2) from prolonged DAPT after percutaneous coronary intervention (PCI). To evaluate the safety and efficacy of DAPT duration according to DAPT score. Retrospective assessment of DAPT score-guided treatment duration in a randomized clinical trial. (ClinicalTrials.gov: NCT00611286). PCI patients. 1970 patients undergoing PCI. DAPT (aspirin and clopidogrel) for 24 versus 6 months. Primary efficacy outcomes were death, myocardial infarction, or cerebrovascular accident. The primary safety outcome was type 3 or 5 bleeding according to the Bleeding Academic Research Consortium definition. Outcomes were assessed between 6 and 24 months. 884 patients (44.9%) had a DAPT score of at least 2, and 1086 (55.1%) had a score less than 2. The reduction in the primary efficacy outcome with 24- versus 6-month DAPT was greater in patients with high scores (risk difference [RD] for score ≥2, -2.05 percentage points [95% CI, -5.04 to 0.95 percentage points]; RD for score <2, 2.91 percentage points [CI, -0.43 to 6.25 percentage points]; P= 0.030). However, the difference by score for the primary efficacy outcome varied by stent type; prolonged DAPT with high scores was effective only in patients receiving paclitaxel-eluting stents (RD, -7.55 percentage points [CI, -12.85 to -2.25 percentage points]). The increase in the primary safety outcome with 24- versus 6-month DAPT was greater in patients with low scores (RD for score ≥2, 0.20 percentage point [CI, -1.20 to 1.60 percentage points]; RD for score <2, 2.58 percentage points [CI, 0.71 to 4.46 percentage points]; P= 0.046). Retrospective calculation of the DAPT score. Prolonged DAPT resulted in harm in patients with low DAPT scores undergoing PCI but reduced risk for ischemic events in patients with high scores receiving paclitaxel-eluting stents. Whether prolonged DAPT benefits patients with high scores treated with contemporary drug-eluting stents requires further study. None.

Long-term ticagrelor monotherapy versus standard dual antiplatelet therapy followed by aspirin monotherapy in patients undergoing biolimus-eluting stent implantation: rationale and design of the GLOBAL LEADERS trial.

The GLOBAL LEADERS trial is a superiority study in patients undergoing percutaneous coronary intervention, with a uniform use of Biolimus A9-eluting stents (BES) and bivalirudin. GLOBAL LEADERS was designed to assess whether a 24-month antithrombotic regimen with ticagrelor and one month of acetylsalicylic acid (ASA), compared to conventional dual antiplatelet therapy (DAPT), improves outcomes. Patients (n >16,000) are randomised (1:1 ratio) to ticagrelor 90 mg twice daily for 24 months plus ASA ≤100 mg for one month versus DAPT with either ticagrelor (acute coronary syndrome) or clopidogrel (stable coronary artery disease) for 12 months plus ASA ≤100 mg for 24 months. The primary outcome is a composite of all-cause mortality or non-fatal, new Q-wave myocardial infarction at 24 months. The key safety endpoint is investigator-reported class 3 or 5 bleeding according to the Bleeding Academic Research Consortium (BARC) definitions. Sensitivity analysis will be carried out to explore potential differences in outcome across geographic regions and according to specific angiographic and clinical risk estimates. The GLOBAL LEADERS trial aims to assess the role of ticagrelor as a single antiplatelet agent after a short course of DAPT for the long-term prevention of cardiac adverse events, across a wide spectrum of patients, following BES implantation.

Impact of preoperative dual antiplatelet therapy on bleeding complications in patients with acute coronary syndromes who undergo urgent coronary artery bypass grafting

BackgroundA 5- to 7-day washout period before coronary artery bypass grafting (CABG) is recommended for patients who have recently received a thienopyridine derivative; however, data supporting this guideline recommendation are lacking in Japanese patients. MethodsUrgent isolated CABG was performed in 130 consecutive patients with acute coronary syndromes (ACS) (101 men; mean age, 69 years). Urgent CABG was defined as operation performed within 5 days after coronary angiography. All patients continued to receive aspirin 100mg/day. The subjects were retrospectively divided into 2 groups: 30 patients with preoperative thienopyridine (clopidogrel in 15 patients, ticlopidine in 15) exposure within 5 days [dual antiplatelet therapy (DAPT) group] and 100 patients without exposure [single antiplatelet therapy (SAPT) group]. ResultsAlthough the DAPT group had a higher proportion of patients who received perioperative platelet transfusions than the SAPT group (50% vs. 18%, p<0.001), intraoperative bleeding (median, 1100ml; interquartile range, 620–1440 vs. 920ml; 500–1100) and total drain output within 48h after surgery (577±262 vs. 543±277ml) were similar. CABG-related major bleeding, which was defined as type 4 or 5 bleeding according to the Bleeding Academic Research Consortium definitions, occurred in a significantly higher proportion of patients in the DAPT group than in the SAPT group (20% vs. 3%, p=0.005). This difference in major bleeding was driven mainly by the higher rate of transfusion of ≥5U red blood cells within a 48-h period in the DAPT group (13% vs. 1%, p=0.01). There was no significant difference in the 30-day composite endpoint including death, myocardial (re)infarction, ischemic stroke, and refractory angina between the DAPT group and SAPT group (17% vs. 19%). ConclusionsPreoperative DAPT increases the risk of CABG-related major bleeding in Japanese patients with ACS undergoing urgent CABG.

Impact of Bleeding on Quality of Life in Patients on DAPT: Insights From TRANSLATE-ACS

BackgroundProlonged dual antiplatelet therapy (DAPT) is recommended after an acute myocardial infarction (AMI) to reduce ischemic events but is associated with increased rates of major and minor bleeding. ObjectivesThis study sought to determine the incidence of post-percutaneous coronary intervention (PCI) bleeding that occurs on contemporary DAPT and its impact on quality of life (QOL). MethodsWe studied 9,290 AMI patients treated with PCI and discharged alive between April 2010 and September 2012. Post-discharge bleeding was categorized according to the Bleeding Academic Research Consortium (BARC) definition. The primary outcome was the 6-month Euro QOL–5 Dimension (EQ-5D) index score (a measure of health utility); a secondary outcome was the EQ-5D visual analog scale (VAS) at 6 months. ResultsOf the 9,290 patients with AMI, bleeding events occurred as follows: any BARC bleeding: 24.2%; BARC 1: 9.1%; BARC 2: 13.8%; BARC 3: 1.1%; BARC 4: 0.03%; and BARC 5: 0%. Those who experienced any BARC bleeding had lower scores across all 5 EQ-5D domains (mobility, self-care, usual activities, pain, and anxiety), as well as lower EQ-5D VAS and EQ-5D index scores. After clinical risk adjustment, any BARC bleeding was independently associated with 6-month EQ-5D index score (p < 0.0001) and lower QOL (p < 0.001). Both the EQ-5D index and the VAS score declined in a stepwise fashion with increasing BARC severity. ConclusionsAmong patients undergoing PCI for AMI, bleeding during follow-up was associated with worse 6-month utility and QOL. Although even minor bleeding was associated with impaired health status and QOL, the degree of impairment increased in a stepwise fashion with bleeding severity.

Abstract 245: Cost Effectiveness and Safety of Abbreviated Eptifibatide Infusion in Veterans Undergoing Percutaneous Coronary Intervention

Background: For patients undergoing percutaneous coronary intervention (PCI), many interventional operators prescribe a bolus of intravenous glycoprotein IIb/IIIa inhibitor during PCI, followed by an infusion for several hours afterward. An abbreviated infusion of eptifibatide has been adopted by many operators based on a small randomized trial from 2009, in which early discontinuation after 2 hours was not inferior to the standard 18-24 hour infusion. However, no subsequent studies have evaluated the safety or cost-effectiveness of the abbreviated infusion among unselected PCI patients. Methods: Of the 1440 patients undergoing PCI at our institution between March 2009 and December 2010, we identified 108 who received the abbreviated eptifibatide infusion (33% undergoing PCI for acute coronary syndrome, 67% for stable coronary disease indications). We used 20 mg vials for bolus followed by 75 mg vials for the 2 hour infusion. All patients were treated with the standard intravenous double-bolus (180 mcg/kg) followed by a weight-based, renally adjusted infusion for 2 hours. For each patient we calculated the cost of the 2 hour infusion at our hospital using the actual amount administered, according to the number of vials required per patient. We then compared these findings to the estimated cost if a standard 18 hour infusion had been administered instead. We also collected data about pre-defined endpoints including: target vessel revascularization (TVR), clinical evidence of myocardial infarction, stroke, death, and stent thrombosis within 30 days of the procedure. In-hospital bleeding events, using the Bleeding Academic Research Consortium (BARC) definitions, were also collected. Results: In our patient population the mean dose required was 55.6 mg, resulting in 2.2 bolus and 1 infusion vials per patient, and an overall cost of $384 per patient receiving the 2 hour infusion. Using the same data for a standard 18 hour infusion, the mean drug dose would have been 224.2 mg, resulting in 2.2 bolus and 3 infusion vials per patient and $838 cost per patient. When comparing the 2 protocols in all 108 patients, using the abbreviated infusion saved 222 infusion vials (67%) and $4905 overall, or 161 mg (2 vials) and $454 cost per patient. Among these 108 patients, there was no TVR, myocardial infarction, stent thrombosis, or death within 30 days. One patient had transient ischemic attack (1%) and one patient had a type 1 minor bleed using the BARC definition (1%). Conclusion: In this real world cohort of patients undergoing PCI, an abbreviated 2 hour eptifibatide infusion after PCI was safe and had a cost savings of greater than 50% per patient, when compared with a standard 18 hour infusion. This approach is more cost-effective and should be considered in patients undergoing PCI who are not pretreated with dual antiplatelet therapy.

Major bleeding risk prediction using Chronic Kidney Disease Epidemiology Collaboration and Modification of Diet in Renal Disease equations in acute coronary syndrome

Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations estimate glomerular filtration rate more accurately than the Modification of Diet in Renal Disease (MDRD) Study equation. Our aim was to evaluate whether CKD-EPI equations based on serum creatinine and/or cystatin C (CysC) predict risk for major bleeding (MB) more accurately than the MDRD Study equation in patients with non-ST-segment elevation acute coronary syndromes (ACS). Three hundred and fifty consecutive subjects with non-ST-segment elevation ACS (68 ± 12 years, 70% male) were studied. Glomerular filtration rate was estimated using the CKD-EPI and MDRD Study equations. The primary endpoint was the occurrence of MB during the follow-up, which was defined according to the Bleeding Academic Research Consortium Definition criteria as bleeding types 3-5. During the median follow-up of 589 days (interquartile range, 390-986), 27 patients had MB (0.04% events per person year). Patients with MB had worse kidney function parameters, regardless of the estimating equation used (P < 0.001). After multivariate Cox regression adjustment, both CysC-based CKD-EPI equations were independent predictors of MB (CKD-EPI(creatinine-cystatin) C per mL/min/1.73 m(2), HR = 0.973 (95%CI 0.955-0.991; P = 0.003) and CKD-EPI(cystatin) C per mL/min/1.73 m(2), HR = 0.976 (95%CI 0.976-0.992; P = 0.003), while the CKD-EPI(creatinine) and MDRD equations did not achieve statistical significance. Both CKD-EPI(creatine-cystatin) C and CKD-EPI(cystatin) C were associated with a significant improvement in MB risk reclassification. In this cohort of non-ST-segment elevation ACS patients with relatively preserved renal function, both CysC-based CKD-EPI equations improved ability to predict risk for MB and were superior to other equations for this application.