Bleeding Academic Research Consortium Definition Research Articles

Incidence, source, and prognostic impact of major bleeding across the spectrum of aortic stenosis

Severe aortic stenosis (AS) has been associated with bleeding. However, there is a lack of prospective assessment of bleeding events and their clinical significance in a large population of outpatients with variable degree of AS severity. To assess the incidence, source, determinants, and prognostic impact of major bleeding in patients with variable degree of AS severity. Between May 2016 and December 2017, consecutive outpatients were included. Major bleeding was defined as type ≥3 bleed using the Bleeding Academic Research Consortium definition. Cumulative incidence was calculated with death as the competing event. Data was censored at time of aortic valve replacement. Among 2,830 patients, 46 major bleeding events occurred (0.7%/year) during a median follow-up of 2.1 years (interquartile range: 1.4-2.7). Most frequent sites of bleeding were gastrointestinal (50%) and intracranial (30.4%). Major bleeding was significantly associated with all-cause mortality (hazard ratio: 5.93 (95% confidence interval 3.64-9.65); P < .001). AS severity was associated with major bleedings (P=.041). By multivariable analysis, severe AS was an independent determinant of major bleeding (hazard ratio vs mild AS: 3.59 [95% confidence interval 1.56-8.29]; P=.003). The increased risk of bleeding associated with severe AS was significantly exacerbated in patients using oral anticoagulation. In AS patients, major bleeding is rare but a strong independent predictor of death. AS severity is a determinant of bleeding events. Severe AS and oral anticoagulation should be identified as an association at very high risk of major bleeding.

The standard versus prolonged dual antiplatelet therapy after the XINSORB bioresorbable scaffold implantation (SPARTA) trial: study protocol for a randomized controlled trial

BackgroundDual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is the standard of care after coronary stenting, including coronary stenting involving bioresorbable scaffolds (BRSs). Current clinical guidelines recommend at least 12 months of DAPT after BRS implantation. However, the correlation between prolonged DAPT and net clinical benefits remains unknown.MethodsThe SPARTA trial is designed to be a prospective, randomized, parallel-group, clinical trial. It aims to compare the benefits and risks of DAPT applied for either 12 or 36 months after XINSORB BRS implantation. The primary endpoints are the incidence of the composite endpoint of major adverse cardiac events (MACEs), including all-cause death, any myocardial infarction (MI), and all revascularizations, as well as Bleeding Academic Research Consortium Definition (BARC) type 3 or 5 bleeding events. The secondary endpoints of the study include the device-oriented composite endpoint of target lesion failure (defined as cardiac death, target vessel-related MI, or ischemia-driven target lesion revascularization), target vessel failure (defined as cardiac death, MI, or ischemia-driven target vessel revascularization), scaffold thrombosis, and minor bleeding events. This trial will enroll 2106 subjects treated with the XINSORB BRS only. All subjects will receive DAPT after the index procedure for 12 (± 1) months. Subjects without MACEs or major bleeding will be randomized to receive either 24 additional months of DAPT or aspirin alone.DiscussionThis trial is designed to investigate the impact of extending the duration of DAPT up to 3 years after XINSORB BRS implantation by investigating the balance of risks and benefits in a broad population of treated patients.Trial registrationClinicalTrials.gov NCT04501900. Registered on 6 August 2020.

Predictors of bleeding events in acute decompensated heart failure patients with antithrombotic therapy: AURORA study.

Heart failure (HF) is reported to be one of the major risks of bleeding events. On the other hand, HF patients frequently receive anticoagulants or antiplatelet therapy to manage various co-morbidities. However, predictors of bleeding events in patients with HF have rarely been reported. This study aimed to evaluate the predictors of bleeding events and relationship between bleeding events and HF re-hospitalizations. We included 1660 acute decompensated heart failure (ADHF) patients from the AURORA registry between January 2015 and December 2020. A total of 1429 patients were excluded because of history of HF admission, missing echocardiographic data at discharge, lost to follow-up, haemodialysis and no antithrombotic drugs. Finally, we evaluated 231 patients from AURORA registry. The bleeding events were defined as Type 2 to 5 bleeding according to the Bleeding Academic Research Consortium definition. We divided our patients into the bleeding group and non-bleeding group. We compared the baseline characteristics, medications, laboratory data, and echocardiographic data between the two groups. Median age was 78 (IQR 71-82) years old and male accounted for 59%. Approximately half of the patients had an antiplatelet therapy and 70% had an anticoagulant therapy. During a median follow-up of 651 (IQR 357-1139) days, 32 patients (13.8%) suffered from bleeding events. The major driver of the registered events was gastrointestinal bleeding (n=21, 65.6%), and the other events were cerebral bleeding (n=4, 12.5%), intraarticular bleeding (n=2, 6.3%), urogenital bleeding (n=2, 6.3%), haemorrhagic pericardial effusions (n=1, 3.1%), subcutaneous hematomas (n=1, 3.1%), and haemothorax (n=1, 3.1%). There was a significantly lower haemoglobin level (P<0.01), higher proportion of inferior vena cava (IVC) diameter ≥21mm (P<0.01), and higher furosemide equivalent doses per kilogram (P<0.01) in the bleeding group than non-bleeding group. A multivariate analysis revealed an equivalent dose of furosemide per kilogram ≥0.66mg/kg (hazard ratios (HR) of 2.64, 95% confidence interval (CI) 1.26-5.68, P=0.01), haemoglobin ≤10.3g/dL (HR of 2.43, 95% CI 1.14-5.03, P=0.02), and IVC diameter ≥21mm (HR of 2.79, 95% CI 1.16-6.29, P=0.02) were independently associated with bleeding events. The Kaplan-Meier analysis showed that HF re-hospitalization rates were higher in the bleeding group than non-bleeding group (P=0.04). High doses of oral loop diuretics, IVC dilatation, and anaemia were predictors of bleeding events in patients hospitalized with ADHF patients. In addition, bleeding events were associated with HF re-hospitalizations.

508 ELIGIBILITY TO DUAL PATHWAY INHIBITION THERAPY IN PATIENTS WITH CORONARY OR PERIPHERAL ARTERY DISEASE

Abstract Background The VOYAGER PAD and COMPASS trials established the benefit of dual pathway inhibition (DPI) with aspirin and low dose rivaroxaban for eligible patients with peripheral artery disease (PAD) undergoing revascularisation and for those with PAD or chronic coronary syndromes (CCS), respectively. However, in-hospital implementation of DPI remains slow in clinical practice, also due to eligibility uncertainties. Purpose To assess the eligibility to DPI among contemporary patients hospitalised in cardiology and vascular surgery units, and to evaluate clinical outcomes of patients presenting with revascularised PAD according to their eligibility to the DPI strategy. Methods We analysed data from patients with revascularised PAD included in the prospective institutional RAPID (RivAroxaban for PerIpheral artery Disease) and applied the VOYAGER PAD criteria to identify patients eligible to DPI and the frequency and distribution of exclusion criteria. Clinical outcomes were compared between patients eligible and not eligible to DPI. The primary efficacy outcome was the composite of cardiovascular death, acute limb ischemia, or unplanned limb revascularization, while the primary safety outcome was major bleeding according to the Bleeding Academic Research Consortium definition (i.e., type 3 or 5). Secondary outcomes included the individual components of the primary efficacy outcome, all-cause death, clinically relevant bleeding and minor bleeding. Finally, to explore the residual potential for DPI applicability in clinical practice, COMPASS criteria were also applied to a contemporary CCS cohort from the institutional registry enrolling coronary artery disease patients undergoing invasive management, and the frequency and characteristics of DPI eligibility between PAD and CCS were compared. Results From May 2021 to August 2022, 122 patients (mean age 70.9±10.1 years, 74.6% male) were included in the RAPID registry. Based on VOYAGER PAD eligibility criteria, 62 patients (50.8%) were eligible to DPI. Main reasons for exclusion were oral anticoagulation (13.1%), prior stroke or transient ischemic attack (11.5%), high bleeding risk (46.7%), or concurrent indications for dual antiplatelet therapy (0.8%). In the CCS registry, 1,389 patients were enrolled in the same period (mean age 70.3±10.5 years, 75.6% male). CCS patients who were eligible to DPI were 276 (19.9%). Main reasons for exclusion were concurrent need for dual antiplatelet therapy (27.1%), high bleeding risk (44.8%), need for oral anticoagulation (21.4%), severe heart failure (9.9%), absence of CAD or PAD (35.3%), and end-stage renal disease (2.6%). To provide updated follow-up information, clinical outcomes will be made available for presentation on December 2022. Conclusions Approximately one patient out of two with revascularised PAD and only one fifth of patients with CCS undergoing invasive management were eligible to DPI. According to these results, unlike candidates to the VOYAGER PAD strategy, candidates to the COMPASS strategy are more likely to be identified in an outpatient than hospital setting.

Performance of the HAS-BLED, ORBIT, and ATRIA Bleeding Risk Scores on a Cohort of 399 344 Hospitalized Patients With Atrial Fibrillation and Cancer: Data From the French National Hospital Discharge Database.

Background The association between cancer types and specific bleeding events in patients with atrial fibrillation has been scarcely investigated. Also, the performance of bleeding risk scores in this high-risk subgroup of patients is unclear. We investigated the rate of any bleeding, intracranial hemorrhage, major bleeding, and gastrointestinal bleeding according to cancer types in patients with atrial fibrillation. We also tested the predictive value of HAS-BLED, ATRIA, and ORBIT bleeding risk scores. Methods and Results Observational retrospective cohort study including hospitalized patients with atrial fibrillation and cancer from the French National Hospital Discharge Database (Programme de Medicalisation des Systemes d'Information) from January 2010 to December 2019. Major bleeding was defined according to Bleeding Academic Research Consortium definitions. Patients with HAS-BLED ≥3, ATRIA ≥5, or ORBIT ≥4 were classified as at high bleeding risk. Receiver operating characteristic analysis for each score against any bleeding, major bleeding, gastrointestinal bleeding, and intracranial hemorrhage was performed. Areas under the curve (AUCs) were then compared. We included 399 344 patients. Mean age was 77.9±10.2 years, and 63.2% were men. The highest intracranial hemorrhage rates were found in leukemia (1.89%/year), myeloma (1.52%/year), lymphoma and liver (1.45%/year), and pancreas cancer (1.41%/year). Receiver operating characteristic analysis showed that ORBIT score predicted best for any bleeding. In addition, ORBIT score ≥4 had the highest predictivity for major bleeding (AUC, 0.805), followed by HAS-BLED ≥3 and ATRIA ≥5 (AUCs, 0.716 and 0.700, respectively). HAS-BLED and ORBIT performed best for intracranial hemorrhage (AUCs, 0.744 and 0.742 for continuous scores, respectively), better than ATRIA (AUC, 0.635). For gastrointestinal bleeding, ORBIT ≥4 had the highest predictivity (AUC, 0.756), followed by the HAS-BLED ≥3 (AUC, 0.702) and ATRIA ≥5 (AUC, 0.662). Conclusions Some cancer types carry a greater bleeding risk in patients with atrial fibrillation. The identification and management of modifiable bleeding risk factors is crucial in these patients, as well as to flag up high bleeding risk patients for early review and follow-up.

Bivalirudin vs. heparin on a background of ticagrelor and aspirin in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: A multicenter prospective cohort study.

Current guidelines recommend potent P2Y12 inhibitors such as ticagrelor over clopidogrel as part of the dual antiplatelet therapy (DAPT) after ST-segment elevation myocardial infarction (STEMI), irrespective of final management strategy. The aim of this multicenter prospective cohort study was to examine the efficacy and safety of bivalirudin with background ticagrelor and aspirin therapy in patients with STEMI undergoing primary percutaneous coronary intervention (PPCI). A total of 800 patients with STEMI who were undergoing PPCI and receiving treatment with aspirin and ticagrelor from three Hospitals between April 2019 and September 2021 were included in this study. The patients were assigned, according to the perioperative anticoagulant, to the bivalirudin group (n = 456) or the heparin group (n = 344). In this study, the primary endpoint was 30-day net adverse clinical events (NACEs), a composite of major adverse cardiac or cerebral events (MACCEs, a composite of cardiac death, recurrent myocardial infarction, ischemia-driven target vessel revascularization, or stroke), or any bleeding as defined by the Bleeding Academic Research Consortium (BARC) definition (grades 1-5). The patients were followed up for 30 days after PPCI. The incidence of NACE was significantly lower in the bivalirudin group than in the heparin group (11.2 vs. 16.0%, P = 0.042), and this significance was mainly a consequence of the reduction in BARC 1 bleeding events in the bivalirudin group compared to the heparin group (3.2 vs. 7.1%, P = 0.010). Results from multivariate Cox regression analysis showed that bivalirudin significantly reduced 30-day NACE (HR: 0.676, 95% CI: 0.462-0.990, P = 0.042) and BARC1 bleeding events (HR: 0.429, 95% CI: 0.222-0.830, P = 0.010). No significant between-group differences were observed for MACCE, all-cause mortality, cardiac death, recurrent myocardial infarction, stroke, target vessel revascularization, stent thrombosis, and BARC2-5 bleeding events at 30 days. In patients with STEMI who were undergoing primary PCI and receiving treatment with aspirin and ticagrelor, bivalirudin was associated with decreased rates in NACE and minimal bleeding events without significant differences in the rates of MACCE or stent thrombosis when compared with heparin. Nevertheless, large randomized trials are warranted to confirm these observations. The trial was registered at the Chinese Clinical Trial Registry (ChiCTR, http://www.chictr.org.cn; identifier [ChiCTR1900022529]). Registered on 15 April 2019. Registration title: Effect of bivalirudin combined with ticagrelor in patients with ST-segment elevation myocardial infarction during primary percutaneous coronary intervention.

Removal of Apixaban during Emergency Cardiac Surgery Using Hemoadsorption with a Porous Polymer Bead Sorbent.

Background: Patients on direct oral anticoagulants are at high risk of perioperative bleeding complications. We analyzed the results of intraoperative hemoadsorption (HA) in patients undergoing cardiac surgery who were also on concurrent therapy with apixaban. Methods: we included 25 consecutive patients on apixaban who underwent cardiac surgery with the use of cardio-pulmonary bypass (CPB) at three sites. The first 12 patients underwent surgery without hemoadsorption (controls), while the next 13 consecutive patients were operated with the Cytosorb® (Princeton, NJ, USA) device integrated into the CPB circuit (HA group). The primary outcome was perioperative bleeding assessed by the Bleeding Academic Research Consortium (BARC) definition and secondary outcomes included 24 h chest-tube-drainage (CTD) and need for 1-deamino-8-d-arginine-vasopressin (desmopressin (DDAVP)) administration to achieve hemostasis. Results: Preoperative mean daily dose of apixaban was higher in the HA group (8.5 ± 2.4 vs. 5.6 ± 2.2 mg, p = 0.005), while time since last apixaban dose was longer in the controls (1.3 ± 0.9 vs. 0.6 ± 1.2 days, p < 0.001). No BARC-4 bleeding events and no repeat-thoracotomies occurred in the HA group compared with 3 and 1, respectively, in the controls. Postoperative 24 h CTD volume was significantly lower in the HA group (510 ± 152 vs. 893 ± 579 mL, p = 0.03) and there was no need for DDAVP compared to controls, who received an average of 10 ± 13.6 mg (p = 0.01). Conclusions: In patients on apixaban undergoing emergent cardiac surgery, the intraoperative use of hemoadsorption was feasible and safe. Compared to patients operated on without hemoadsorption, BARC-4 bleeding complications did not occur and the need for 24 h CTD and DDAVP was significantly lower.

Bleeding risk prediction in a large cohort of patients with atrial fibrillation and cancer: a nationwide cohort study

Abstract Introduction The association between cancer types and specific bleeding events in atrial fibrillation (AF) patients has been scarcely investigated. Also, the performance of bleeding risk scores in this high-risk subgroup of patients is unclear. Purpose We investigated the rate of intracranial haemorrhage (ICH), major (MB) and gastrointestinal bleeding (GB) according to cancer types in AF patients. We also tested the predictive value of HAS-BLED, ATRIA and ORBIT bleeding risk scores. Methods Observational retrospective cohort study including 399,344 AF patients with cancer (mean age 77.9±10.2 years; 63.2% men). MB was defined according to Bleeding Academic Research Consortium (BARC) definitions. Results The highest ICH rates were found in leukaemia (1.89%/year), myeloma (1.52%/year), lymphoma and liver (1.45%/year) and pancreas cancer (1.41%/year). GBs were highest in liver (7.54%/year), pancreas (7.42%/year) and gastric (5.51%/year). Receiver operating characteristic (ROC) analysis showed that an ORBIT score ≥4 had the highest predictivity for MBs (AUC 0.805) followed by HAS-BLED and ATRIA (AUC 0.716 and 0.700, respectively). HAS-BLED and ORBIT performed best for ICH (AUC 0.744 and 0.742, respectively), better than ATRIA (AUC 0.635). For GB, ORBIT ≥4 had the highest predictivity (AUC 0.756), followed by the HAS-BLED (AUC 0.702) and ATRIA (AUC 0.662). Conclusions Some cancer types carry a greater bleeding risk in AF patients. The identification and management of modifiable bleeding risk factors is crucial in these patients, as well as to flag up high bleeding risk patients for early review and follow-up Conclusions Some cancer types carry a greater bleeding risk in AF patients. The identification and management of modifiable bleeding risk factors is crucial in these patients, as well as to flag up high bleeding risk patients for early review and follow-up. Funding Acknowledgement Type of funding sources: None.

Bleeding outcomes with ticagrelor versus clopidogrel in patients with acute coronary syndrome; a focused analysis from the multicenter CREA ARIAM Andalucia registry

Abstract Background/Introduction With the advent of more potent antithrombotic agents, bleeding has emerged as an important safety concern in patients with acute coronary syndrome (ACS). Moreover, hemorrhagic complications have been strongly linked with subsequent mortality in this clinical scenario. Purpose We sought to determine the incidence, types, timing and prognostic relevance of major bleeding events in ACS patients treated with ticagrelor or clopidogrel in contemporary practice. Methods Prospective, observational, multicentre all-comers registry of ACS patients who were intended to receive a 12-month DAPT course with ticagrelor or clopidogrel. Major bleeding was defined as a type 3 or 5 bleed using the Bleeding Academic Research Consortium (BARC) definition. Bleeding was further classified according to the anatomic location. All bleeding episodes were analysed accounting for death as a competing event, using competing risk regression models based on the on-treatment principle (i.e., according to the P2Y12 inhibitor actually received from date of index admission until either time of DAPT cessation plus 14 days or censoring, whichever occurred first). Results Among 2070 patients surviving to hospital discharge (mean age 63 years, 27% women, 62.5% STEMI), 106 (5.3%, 0.6%/year) experienced major bleeding event at a median time of 92 days (interquartile range, 6–187 days) after discharge. Most events (n=59, 55.7%) were BARC type 3a bleeds with 2 fatal bleeds (type 5b). In most cases (53%), the site of bleeding was gastrointestinal, followed by intracranial (n=13, 12%). After adjustments for baseline predictors, ticagrelor was associated with increased but not statistically significant risk of major bleeding compared with clopidogrel (5.6% vs 5.2%, adjusted hazard ratio [aHR] 1.40, 95% CI 0.96–2.05; P=0.075). Major bleeding was significantly associated with nearly 2-fold higher risk of mortality (aHR 1.94; 95% CI 1.32–2.86; P=0.001), irrespective of P2Y12 inhibitor treatment (P interaction = 0.159). Conclusion(s) Bleeding was not rare within 1 year after index ACS, with incidence rates peaked at 30 to 60 days post-index admission. The most common bleeding site was gastrointestinal followed by intracranial haemorrhage. Ticagrelor use was not associated with significantly increased risk of major bleeding compared with clopidogrel whereas bleeding led to a nearly 2-fold higher risk of major bleeding. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Astra-Zeneca

Transcatheter aortic valve implantation in patients with uninterrupted vitamin K antagonists.

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 transcatheter aortic valve implantation (TAVI). The aim of this study was to evaluate the rate of major bleeding and vascular complications after TAVI performed in patients with uninterrupted VKA. From January 2016 to October 2017, consecutive patients who underwent TAVI with uninterrupted VKA (International Normalized Ratio [INR]between 1.5 and 3.5) were prospectively included in a monocentric registry. TAVI was performed according to current guidelines and a 50 U/kgbolus 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 3 (VARC3) and the Bleeding Academic Research Consortium (BARC) definitions at a 30-day follow-up. A total of 88 patients were included with a median age of 84 years (81.8-87.0), 42% being female. The median society of thoracic surgeons score was 5.1 (4.1-7.5), the median CHADS2-VAScwas 5.5 (5-6)and 60.2% had a chronic kidney failure. Median INR at the time of implantation was 2.1 (1.8-2.6). The main VKA indication was atrial fibrillation. Transfemoral access was used in 88.6% of the patients. Major bleeding (BARC ≥ 3b) occurred in five patients (5.7%) and major vascular complications occurred in seven patients (8.0%). At 1month follow-up, major bleeding (BARC ≥ 3) or vascular complications occurred in 10 patients (11.4%). In patients with major bleeding peripheral arterial disease (RR = 10.95; 95% confidence interval (CI) 1.63-73.75; p = 0.014) and carotid access (RR = 8.56; 95% CI 1.19-1.51; p = 0.033) were more common. INR > 2.5 was significantly associated with vascular complications (RR = 7.14; 95% CI 1.29-39.63; p = 0.025). At 30 days, mortality and stroke rates were 2.3% and 4.5%, respectively. TAVI with uninterrupted VKA treatment seems feasible and safe with a low risk of major bleeding and vascular complications in this first single-center experience. Particular caution is advocated in high body mass index patients and to keep INR < 2.5.

Bleeding outcomes with ticagrelor versus clopidogrel in patients with acute coronary syndrome. A focused analysis from the multicenter CREA-ARIAM Andalucia registry

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): The study project was financially supported by a no conditional grant (AstraZeneca) Background/Introduction With the advent of more potent antithrombotic agents, bleeding has emerged as an important safety concern in patients with acute coronary syndrome (ACS). Moreover, hemorrhagic complications have been strongly linked with subsequent mortality in this clinical scenario. Purpose We sought to determine the incidence, types, timing and prognostic relevance of major bleeding events in ACS patients treated with ticagrelor or clopidogrel in contemporary practice. Methods Prospective, observational, multicentre all-comers registry of ACS patients who were intended to receive a 12-month DAPT course with ticagrelor or clopidogrel. Major bleeding was defined as a type 3 or 5 bleed using the Bleeding Academic Research Consortium (BARC) definition. Bleeding was further classified according to the anatomic location. All bleeding episodes were analysed accounting for death as a competing event, using competing risk regression models based on the on-treatment principle (i.e., according to the P2Y12 inhibitor actually received from date of index admission until either time of DAPT cessation plus 14 days or censoring, whichever occurred first). Results Among 2070 patients surviving to hospital discharge (mean age 63 years, 27% women, 62.5% STEMI), 106 (5.3%, 0.6%/year) experienced major bleeding event at a median time of 92 days (interquartile range, 6–187 days) after discharge. Most events (n=59, 55.7%) were BARC type 3a bleeds with 2 fatal bleeds (type 5b). In most cases (53%), the site of bleeding was gastrointestinal, followed by intracranial (n=13, 12%). After adjustments for baseline predictors, ticagrelor was associated with increased but not statistically significant risk of major bleeding compared with clopidogrel (5.6% vs 5.2%, adjusted hazard ratio [aHR] 1.40, 95% CI 0.96 – 2.05; P = .075). Major bleeding was significantly associated with nearly 2-fold higher risk of mortality (aHR 1.94; 95% CI 1.32– 2.86; P = .001), irrespective of P2Y12 inhibitor treatment (P interaction = .159). Conclusion(s) Bleeding was not rare within 1 year after index ACS, with incidence rates peaked at 30 to 60 days post-index admission. The most common bleeding site was gastrointestinal followed by intracranial haemorrhage. Ticagrelor use was not associated with significantly increased risk of major bleeding compared with clopidogrel whereas bleeding led to a nearly 2-fold higher risk of major bleeding.

Primary Percutaneous Coronary Intervention with High-Bolus Dose Tirofiban: The FASTER (Favorite Approach to Safe and Effective Treatment for Early Reperfusion) Multicenter Registry.

Objectives To investigate the safety and clinical efficacy of tirofiban during primary percutaneous coronary interventions (pPCI). Background Gp IIb/IIIa inhibitors (GPI) use during pPCI has declined over years, mainly for the increased hemorrhagic risk associated to their use and for the availability of potent, fast-acting oral antiplatelet drugs. However, several pharmacodynamic studies showed suboptimal platelet inhibition with P2Y12-blockers, such as prasugrel or ticagrelor. Methods Patients with ST-segment elevation myocardial infarction (STEMI) undergoing pPCI were prospectively enrolled in a multicenter registry conducted in high-volume centers in Italy. All patients received intraprocedural tirofiban. The primary safety endpoint was the occurrence of in-hospital bleedings according to the Bleeding Academic Research Consortium definition. In-hospital major adverse coronary events (MACE, defined as death, reinfarction, stent thrombosis, and target vessel revascularization), final TIMI flow, myocardial blush grade, and ST-segment resolution were also evaluated. Results A total of 472 patients (mean age 61 ± 11 years, 83% males) were enrolled in 16 Italian centers from October 2015 to June 2018. Mean basal thrombus grade score was 3.47 ± 1.25. PCI was performed by transradial approach in 88% of patients. We observed a very low rate of 30 days BARC bleedings (2.1%) and MACE (0.8%). Complete (>70%) ST-segment resolution was observed in 67% of patients. Conclusions In the FASTER registry, the use of tirofiban during primary PCI, performed with a transradial approach in most cases, in patients with high thrombus burden was associated with high rates of complete ST-segment resolution and low rates of in-hospital bleeding and MACE.

Abstract 9477: Relation Between Coronary Artery Calcium Score and Clinical Outcomes After Percutaneous Coronary Intervention in Stable Coronary Artery Disease

Introduction: Recently, some consensus on high bleeding and thrombotic risk has been reported in the management of patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). However, none of the currently available risk scores includes coronary artery calcification (CAC) score. The usefulness of the assessment of coronary artery calcium on the net adverse clinical event (NACE) in patients with stable CAD undergoing PCI remains understudied. This study aimed to evaluate the association between the CAC score measured by multidetector computed tomography (MDCT) and clinical outcomes after percutaneous coronary intervention (PCI) in stable CAD patients. Methods: We conducted a retrospective observational study including 134 consecutive patients who underwent MDCT and were scheduled for the first elective PCI. The patients were divided into 2 groups based on the CAC score [low (≤ 400) and high (&gt; 400) CAC score]. High bleeding risk was assessed using the Academic Research Consortium for high bleeding risk (ARC-HBR) and the Japanese Circulation Society High Bleeding Risk (JCS-HBR) criteria. The clinical outcome was NACE that was defined as a composite of all-cause death, myocardial infarction (MI), stroke, target lesion revascularization (TLR), stent thrombosis, and major bleeding. According to the Bleeding Academic Research Consortium (BARC) definition, major bleeding was defined as BARC 3 and 5. Results: The high CAC score group was significantly associated with NACE than the low CAC group (22.0% vs 7.5%, P = 0.019). The Cox regression analyses showed that CAC score but not HBR-positive was a significant prognostic factor for NACE (HR, 3.27; 95% CI, 1.14-10.4; p &lt; 0.028, HR, 1.12; 95% CI, 0.37-3.21; p = 0.834, respectively). The Kaplan-Meier survival curves showed that the high CAC group had a higher frequency of NACE events compared with the low CAC group (p = 0.012). Conclusions: The association of high CAC score with NACE including thrombotic and bleeding events were observed in patients with stable CAD, indicating that high CAC was independently related to being a predictor for NACE after PCI.

The monocyte to high-density lipoprotein cholesterol ratio and outcomes in type 2 diabetes mellitus patients with non-ST-segment elevation acute coronary syndrome.

BackgroundThe monocyte to high-density lipoprotein cholesterol ratio (MHR) has been demonstrated as a new marker of inflammation. However, at present, the prognostic value of MHR in type 2 diabetes mellitus (T2DM) accompanied with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) undergoing percutaneous coronary intervention (PCI) is unclear.MethodsT2DM patients with NSTE-ACS undergoing PCI were consecutively enrolled from January 1, 2010 to December 31, 2014 and divided according to MHR value tertiles. Baseline, procedural, and follow-up data were collected. The primary outcomes were in-hospital major adverse clinical events (MACE). The prespecified secondary outcomes included any bleeding [as indicated by Bleeding Academic Research Consortium definition (BARC) grades 1–5] and death during follow-up.ResultsOf the 1,405 enrolled patients, the rates of in-hospital MACE (0.2%, 0.2%, and 1.3%, P=0.043) and bleeding (12.4%, 12.2%, and 17.1%, P=0.048) increased significantly in high MHR tertiles. After 1 year of follow-up, the rates of bleeding (15.0%, 14.5%, and 22.2%, P=0.002) and all-cause death (1.5%, 1.7%, and 4.3%, P=0.010) were higher in higher MHR tertiles. Our results also suggested that MHR was an independent predictor of in-hospital MACE [adjusted odds ratio =8.36; 95% confidence interval (CI): 1.57–44.47; P=0.013] and long-term bleeding (adjusted hazard ratio =1.21; 95% CI: 1.07–1.37; P=0.002). Receiver-operating characteristic curve analysis indicated that MHR >0.022 had a sensitivity of 75.0% and specificity of 72.7% for predicting in-hospital MACE [area under the curve (AUC) =0.722; 95% CI: 0.51–0.933; P=0.040]. Furthermore, Kaplan-Meier curves showed that a higher risk of all-cause death in long-term follow-up was prevalent in patients with high MHR (P=0.033).ConclusionsThe increased level of MHR was related to in-hospital MACE and long-term bleeding events in T2DM patients with NSTE-ACS undergoing PCI.

Interaction between thrombin potential and age on early clinical outcome in patients hospitalized for COVID-19

Patients with Coronavirus Disease-2019 (COVID‐19) have haemostatic dysfunction and are at higher risk of thrombotic complications. Although age is a major risk factor for outcome impairment in COVID-19, its impact on coagulative patterns here is still unclear. We investigated the association of Endogenous Thrombin Potential (ETP) with thrombotic and haemorrhagic events according to different ages in patients admitted for COVID-19. A total of 27 patients with COVID‐19-related pneumonia, without need for intensive care unit admission or mechanical ventilation at hospital presentation, and 24 controls with non-COVID-19 pneumonia were prospectively included. ETP levels were measured on admission. Patients were evaluated for major adverse cardiovascular events (MACE: cardiovascular death, myocardial infarction, stroke, transient ischemic attack, venous thromboembolism) and bleeding complications [according to Bleeding Academic Research Consortium (BARC) definition] during in-hospital stay. COVID-19 patients had similar ETP levels compared to controls (AUC 93 ± 24% vs 99 ± 21%, p = 0.339). In the COVID-19 cohort, patients with in-hospital MACE showed lower ETP levels on admission vs those without (AUC 86 ± 14% vs 95 ± 27%, p = 0.041), whereas ETP values were comparable in patients with or without bleeding (AUC 82 ± 16% vs 95 ± 26%, p = 0.337). An interaction between age and ETP levels for both MACE and bleeding complications was observed, where a younger age was associated with an inverse relationship between ETP values and adverse event risk (pint 0.018 for MACE and 0.050 for bleeding). Patients with COVID-19 have similar thrombin potential on admission compared to those with non-COVID-19 pneumonia. In younger COVID-19 patients, lower ETP levels were associated with a higher risk of both MACE and bleeding.

Ischemic and Bleeding Events of Ticagrelor Monotherapy in Korean Patients With and Without Diabetes Mellitus: Insights From the TICO Trial.

Background: Ticagrelor monotherapy after 3 months dual antiplatelet therapy (DAPT) with aspirin and ticagrelor can reduce bleeding without increasing ischemic events after percutaneous coronary intervention (PCI). However, the impact of this approach among the patient with diabetes remains unknown. Methods: This was a sub-analysis of the Ticagrelor Monotherapy after 3 months in the Patients Treated with New Generation Sirolimus Eluting Stent for Acute Coronary Syndrome (TICO) trial. After successful PCI, the patients were randomly assigned to ticagrelor monotherapy after 3-months DPAT or to ticagrelor-based 12-months DAPT. We compared ischemic events and bleeding events between the patients with diabetes and without diabetes for 12 months. Ischemic events were defined as death, myocardial infarction, ischemic stroke, transient ischemic attack, stent thrombosis, and any revascularizations. Bleeding events were defined according to the Thrombolysis in Myocardial Infarction (TIMI) criteria and Bleeding Academic Research Consortium (BARC) definition. Results: Between August 2015 and October 2018, 3,056 patients were enrolled in the TICO trial, of which 835 (27.3%) had diabetes mellitus. Diabetes mellitus was associated with all evaluated ischemic and bleeding events. No significant differences in any ischemic events were observed in patients with diabetes between ticagrelor monotherapy after 3-months DAPT and ticagrelor-based 12-months DAPT (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.45–1.52, p = 0.540). In patients with diabetes, the overall incidence of bleeding complications during the 12-months follow-up period did not differ between the two treatment groups (HR 0.83, 95% CI 1.48–1.43, p = 0.505). However, ticagrelor monotherapy was significantly reduced both any TIMI bleeding and BARC three or five bleeding events in diabetes patients in the 3-months landmark analysis, after 3-months DAPT period (HR 0.20, 95% CI 0.07–0.59, p = 0.003). Conclusion: In diabetic patients, ticagrelor monotherapy showed a lower incidence of bleeding complications after 3-months DAPT period, without increasing ischemic complications, compared with ticagrelor-based 12-months DAPT (ClinicalTrials.gov Identifier: NCT02494895).

Abstract 15440: Bleeding Complications May Outweigh the Risk of Thrombosis in Patients With End-stage Liver Disease Taking Dual Antiplatelet Therapy After Percutaneous Coronary Intervention

Introduction: Randomized trials have demonstrated the safety and efficacy of one month of dual antiplatelet therapy (DAPT) after placement of drug-eluting stents in patients with high bleeding risk. Patients with end-stage liver disease (ESLD) are underrepresented in these trials. Patients who undergo percutaneous coronary intervention (PCI) in preparation for orthotopic liver transplantation (OLT) exhibit a high incidence of bleeding complications on DAPT. The rates of bleeding versus thrombotic complications in ESLD patients placed on DAPT following PCI are poorly described. Methods: We retrospectively collected data from 61 patients who were evaluated for OLT between 2016 and 2019 and underwent PCI prior to listing. Bleeding events were classified using the Bleeding Academic Research Consortium (BARC) definitions and included if the following criteria were met: events occurred in the setting of DAPT, were non-procedural in etiology, and occurred during the time following PCI and prior to OLT. Ischemic complications were evaluated by the incidence of myocardial infarction (MI), stent thrombosis, in-stent restenosis (&gt;50%) and all-cause mortality at 1 year follow-up. Results: A total of 55/61 patients (90%) were placed on DAPT following PCI. Among them, 21/55 patients (38%) bled while taking DAPT, including 15 patients (27%) with BARC types 3-5 first-time bleeding events and 10 patients (18%) requiring early discontinuation of therapy. The median time to first bleeding event was 8 days (range 1 to 477 days, 85 th percentile 17 days). Among ischemic complications, MI occurred in 11/55 patients (20%) however only one patient had a type 1 MI with the remaining being type 2 in etiology. There were no episodes of stent thrombosis and 2 episodes of in-stent restenosis during the 1 year follow-up. A total of 12/55 patients (22%) went on to receive OLT and 18/55 (33%) passed away by 1 year post-PCI. Conclusions: Patients with ESLD exhibit a high rate of clinically significant bleeding on DAPT when compared to overall thrombotic events. The majority of bleeds occurred within the first month after PCI. These findings illustrate the need for larger studies to assess the safety of single instead of dual antiplatelet therapy in patients with ESLD who receive PCI.

Intermediate versus standard-dose prophylactic anticoagulation and statin therapy versus placebo in critically-ill patients with COVID-19: Rationale and design of the INSPIRATION/INSPIRATION-S studies

BackgroundMicrovascular and macrovascular thrombotic events are among the hallmarks of coronavirus disease 2019 (COVID-19). Furthermore, the exuberant immune response is considered an important driver of pulmonary and extrapulmonary manifestations of COVID-19. The optimal management strategy to prevent thrombosis in critically-ill patients with COVID-19 remains unknown. MethodsThe Intermediate versus Standard-dose Prophylactic anticoagulation In cRitically-ill pATIents with COVID-19: An opeN label randomized controlled trial (INSPIRATION) and INSPIRATION-statin (INSPIRATION-S) studies test two independent hypotheses within a randomized controlled trial with 2 × 2 factorial design. Hospitalized critically-ill patients with reverse transcription polymerase chain reaction confirmed COVID-19 will be randomized to intermediate-dose versus standard dose prophylactic anticoagulation. The 600 patients undergoing this randomization will be screened and if meeting the eligibility criteria, will undergo an additional double-blind stratified randomization to atorvastatin 20 mg daily versus matching placebo. The primary endpoint, for both hypotheses will be tested for superiority and includes a composite of adjudicated acute arterial thrombosis, venous thromboembolism (VTE), use of extracorporeal membrane oxygenation, or all-cause death within 30 days from enrollment. Key secondary endpoints include all-cause mortality, adjudicated VTE, and ventilator-free days. Key safety endpoints include major bleeding according to the Bleeding Academic Research Consortium definition and severe thrombocytopenia (platelet count <20,000/fL) for the anticoagulation hypothesis. In a prespecified secondary analysis for non-inferiority, the study will test for the non-inferiority of intermediate intensity versus standard dose anticoagulation for major bleeding, considering a non-inferiority margin of 1.8 based on odds ratio. Key safety endpoints for the statin hypothesis include rise in liver enzymes >3 times upper normal limit and clinically-diagnosed myopathy. The primary analyses will be performed in the modified intention-to-treat population. Results will be tested in exploratory analyses across key subgroups and in the intention-to-treat and per-protocol cohorts. ConclusionsINSPIRATION and INSPIRATON-S studies will help address clinically-relevant questions for antithrombotic therapy and thromboinflammatory therapy in critically-ill patients with COVID-19.

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.