Secondary Safety Endpoints Research Articles

Changes of antithrombotic prescription in atrial fibrillation patients with acute coronary syndrome or percutaneous coronary intervention and the subsequent impact on long-term outcomes: a longitudinal cohort study

ObjectivesThe choice of optimal antithrombotic therapy in atrial fibrillation (AF) patients with acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI) remains controversial. The aim of this longitudinal cohort study is to investigate the prescribing pattern of antithrombotic regimen in different cohorts and its subsequent impact.Setting and designLongitudinal data from the Tri-Service General Hospital-Coronary Heart Disease (TSGH-CHD) registry, between January 2016 and August 2018 was screened.Participants and methodPatients with prior history of nonvalvular AF, who had ACS presentation or underwent PCI were selected, and these patients were divided into cohort 1 and cohort 2, according to the index date of antithrombotic prescription before and after the PIONEER AF-PCI study.Primary and secondary outcomesThe primary safety endpoints were composites of major bleeding and/or clinically relevant non-major bleeding. The secondary efficacy endpoints included the occurrence of all-cause mortality, stroke/systemic embolization, nonfatal myocardial infarction (MI), and >30-days coronary revascularization.ResultsA total of 121 patients were included into analysis (cohort 1=35; cohort 2=86). Comparing with cohort 1, the prescription rate of triple antithrombotic therapy (TAT) increased from 17.1 to 38.4%, especially the regimen with dual antiplatelet therapy (DAPT) plus low-dose non-vitamin-K dependent oral anticoagulation (NOAC). However, the prescription rate of dual antithrombotic therapy (DAT) decreased (14.3–10.5%), as well as the prescription rate of DAPT (68.6–51.2%). These changes of antithrombotic prescription across different cohorts were not associated with risk of adverse safety (HR= 0.87; 95% CI, 0.42-1.80, p=0.710) and efficacy outcomes (HR=0.96; 95% CI, 0.40-2.32, p=0.930).ConclusionsEntering the NOAC era, the prescription of TAT increased alongside the decrease in DAT. As the prescription rate of DAPT without anticoagulation remained high, future efforts are mandatory to improve the implementation of guidelines and clinical practice.

Efficacy and safety of percutaneous closure of ventricular septal rupture after acute myocardial infarction: a clinical study of 69 cases

Objective: To investigate the efficacy and safety of percutaneous closure of ventricular septal rupture (VSR) after acute myocardial infarction (AMI) and the risk factors of all-cause mortality at 30 days after operation. Methods: This is a retrospective case series study. A total of 69 patients with post-AMI VSR, underwent percutaneous closure of VSR from October 2013 to May 2020 in Department of Cardiology of Henan Provincial People's Hospital and Department of Cardiology of Central China Fuwai Hospital, were included. Patients were divided into survival group (53 cases) and non-survival group (16 cases) according to the status at 30 days after operation. Clinical data were collected and analyzed during hospitalization. Telephone follow-up was performed 30 days after operation. The primary safety endpoint was occlusion failure and all-cause mortality at 30 days post operation. The secondary safety endpoint was the operation related or non-operation related complications. Efficacy endpoint included NYHA classification of cardiac function, index measured by right heart catheterization and echocardiography. Multivariate logistic regression was performed to analyze the risk factors of all-cause mortality at 30 days after operation. Results: A total of 69 patients, aged 67 (64, 71) years, including 42 women (60.9%), were enrolled in this study. All-cause death occurred in 16 patients (23.2%), including 13 in-hospital death and 3 death during follow-up. There were 4 cases of closure failure (5.8%). Among the 65 patients with successful closure, 12 (18.5%) experienced operation-related complications, among which 8 (12.3%) experienced valve injury. The mortality was significantly higher in patients with operation-related complications than that in patients without operation-related complications (41.7% (5/12) vs. 13.2% (7/53), P = 0.022). One case received percutaneous closure of VSR and PCI, this patient experienced new-onset AMI immediately post procedure and died thereafter (1.5%). One case (1.5%) developed multiple organ failure and 2 cases (3.1%) developed gastrointestinal bleeding post operation. All of the 65 patients with successful occlusion completed postoperative echocardiography, 56 patients completed cardiac function assessment at discharge, and 53 patients who survived up to 30 days post discharge completed clinical follow up by telephone. The NYHA cardiac function at discharge and 30 days after operation were significantly improved as compared to that before operation (P<0.001), the ratio of NYHA Ⅰ and Ⅱ patients was significantly higher post operation at these two time points as compared to baseline level (76.8% (43/56) vs. 23.1% (15/65), P<0.001, 77.4% (41/53) vs. 23.1% (15/65), P<0.001). The pulmonary circulation/systemic circulation blood flow ratio (Qp/Qs), pulmonary artery systolic pressure (PASP) and left ventricular end-diastolic diameter (LVDd) were decreased, aortic systolic pressure (ASP) and left ventricular ejection fraction (LVEF) were increased post operation (P<0.05). Multivariate logistic regression analysis showed that WBC>9.8×109/L (OR=20.94, 95%CI 1.21-362.93, P=0.037) and NT-ProBNP>6 000 ng/L (OR=869.11, 95%CI 2.93-258 058.34, P=0.020) were the independent risk factors of mortality at 30 days. Conclusions: Percutaneous closure in VSR after AMI is safe and effective. The increase of WBC and NT-ProBNP are the independent risk factors of all-cause mortality at 30 days after operation.

Long-Term Safety and Clinical Outcomes with Insulin Degludec/Insulin Aspart Treatment in Japanese Patients with Diabetes: A Real-World, Prospective, Observational Study

IntroductionInsulin degludec/insulin aspart (IDegAsp) provides effective glycaemic control with an acceptable safety profile in Japanese patients with diabetes in randomised clinical trials. This post-marketing surveillance study assessed long-term safety and clinical outcomes with IDegAsp in a Japanese real-world setting.MethodsMulticentre, prospective, observational, open-label, single-arm study of Japanese patients with diabetes requiring insulin therapy, who had switched to IDegAsp at their treating physician’s discretion in clinical practice. One year after initiating IDegAsp, incidence of adverse events (AEs [primary endpoint]), serious AEs, adverse drug reactions (ADRs), and severe hypoglycaemia (secondary safety endpoints) were assessed in the safety analysis set (SAS). Secondary effectiveness endpoints were change from baseline in glycated haemoglobin (HbA1c) and fasting plasma glucose (FPG) in the effectiveness analysis set (EAS).ResultsOverall, 1321 patients were included (SAS, n = 1321; EAS, n = 1285); 4.2% with type 1 diabetes, 95.2% with type 2 diabetes, 0.7% with other/unknown diabetes type. In total, 204 AEs were reported in 132 patients (10.0% of the SAS), at a rate [95% confidence interval (CI)] of 16.2 events/100 patient-years of exposure (PYE) [14.0; 18.4]. By preferred term, ‘hypoglycaemia’ was the most frequent AE (45 events in 31 patients [2.3%]; rate [95% CI] 3.6 events/100 PYE [2.5; 4.6]). Serious AEs occurred in 4.2% of patients (rate [95% CI] 5.7 events/100 PYE [4.4; 7.0]), and ADRs in 3.1% (rate [95% CI] 4.6 reactions/100 PYE [3.4; 5.8]). Six events of severe hypoglycaemia were reported in five patients (0.4%; rate [95% CI] 0.5 events/100 PYE [0.1; 0.9]). Change from baseline to 1 year was − 0.51% and − 32.1 mg/dL for HbA1c and FPG, respectively (P < 0.0001 for both).ConclusionIn Japanese patients with diabetes, initiation of IDegAsp in real-world clinical practice was well tolerated, with no new safety signals, and associated with improved glycaemic control after 1 year. Trial RegistrationClinicalTrials.gov identifier, NCT02821052.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-021-01978-2.

Rationale and Design of an Observational Multicenter Study to Evaluate the Use and Effectiveness of Avatrombopag in Adult Patients with Immune Thrombocytopenia: The Adopt Study

Background: Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by low platelet counts caused by a combination of both impaired platelet production and increased peripheral platelet destruction. Current first-line ITP treatments include glucocorticoids and intravenous immunoglobulin (IVIG). However, these drugs have variable and transient efficacy, significant toxicities, and relapse is common upon discontinuation. Subsequent treatment options include the thrombopoietin receptor agonists (TPO-RAs). Avatrombopag (AVA) is an orally administered small molecule TPO-RA. It binds to the human TPO receptor (c-Mpl) at a site that is different from the endogenous TPO binding, stimulating signal transduction and mimicking the biological effects of endogenous TPO. In phase 2 and 3 studies in patients with ITP, AVA was administered to 128 patients for a median duration of 7 months (maximum duration >2 years; Birhiray R, et al. EHA 2020). In a phase 3 trial (NCT01438840), the primary efficacy endpoint of cumulative number of weeks with platelet count ≥50×10 9/L during 6 months of treatment in the absence of rescue therapy was statistically significant favoring AVA over placebo. The most common treatment-emergent adverse events (AEs) in these phase 2 and 3 trials were headache, fatigue, and contusion. AVA has no significant hepatotoxicity and is administered with food without restrictions on meal composition. AVA is approved by FDA and EMA for the treatment of primary chronic ITP in adult patients who are refractory to other treatments (e.g. corticosteroids, IVIG). However, there is a need to provide data to treaters and the ITP community on the real-world usage and effectiveness of AVA (including patients previously treated with TPO-RAs). Described here is the rationale and design of the ADOPT study (NCT04943042), evaluating the use and effectiveness of AVA in adult patients with ITP in routine clinical practice in Europe.Study design and methods: This is a multicenter, observational, phase 4 study, with the primary objective to describe the real-world effectiveness of AVA treatment over a prospective period of 12 months in adult patients with ITP. Prospective data will be collected at routine clinical visits. In addition, retrospective data will be collected from patients' medical records for up to 12 months prior to AVA treatment start.Eligible patients must be ≥18 years, have provided informed consent, have an established and well documented ITP diagnosis, and are treated with or initiating treatment with AVA for ITP at enrollment. Decision to initiate treatment shall be made by the treating physician, independently from the decision to include the patient in the study.Exclusion criteria include enrollment in other clinical interventional study or intake of an investigational medicinal product ≤3 months prior to inclusion, and secondary ITP.The primary endpoint is cumulative number of weeks with a platelet count ≥30×10 9/L during AVA treatment. Platelet counts during rescue medication use and within 4 weeks after stopping a rescue medication or following splenectomy are considered non-response and thus not included in the primary endpoint cumulative number.Secondary endpoints supporting the primary objective include cumulative number of weeks with a platelet count ≥50×10 9/L, patients (n [%]) with a platelet count ≥30×10 9/L and ≥50×10 9/L for at least 8 consecutive weeks, patients (n [%]) experiencing WHO bleeding grade ≥2, patients (n [%]) requiring rescue medication, and time from AVA treatment start to platelet count ≥30×10 9/L and ≥50×10 9/L. Additional secondary endpoints are AVA dose and dosing frequency, reason for ITP treatment discontinuation or change from one ITP treatment to another (prior to and during the study), use of concomitant ITP medications, physician satisfaction with outcome of AVA treatment (5-point scale), physician assessment of clinical change of AVA treatment (Clinical Global Impression of Change scale), healthcare resource use, as well as a number of patient reported outcomes (Table 1). Secondary safety endpoints include serious AEs, AEs of special interest (thromboembolic events, significant bleeding) and AEs leading to AVA discontinuation.Data will be summarized using descriptive statistics.Study status: The study is planned to start 2021 and aims to enroll 150 patients. [Display omitted] DisclosuresMcDonald: Grifols: Research Funding; Bayer, Sobi, Novartis, Amgen, argenx: Honoraria. Matzdorff: Grifols: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria; Argenx: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; UCB: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Current holder of individual stocks in a privately-held company. Mellbring: Sobi: Current Employment. Nazir: Sobi: Current Employment. Lindqvist: Sobi: Current Employment. Santagostino: Sobi: Current Employment.

Post-ST-Segment Elevation Myocardial Infarction Follow-Up Care During the COVID-19 Pandemic and the Possible Benefit of Telemedicine: An Observational Study.

Background: Infectious control measures during the COVID-19 pandemic have led to the propensity toward telemedicine. This study examined the impact of telemedicine during the pandemic on the long-term outcomes of ST-segment elevation myocardial infarction (STEMI) patients.Methods: This study included 288 patients admitted 1 year before the pandemic (October 2018–December 2018) and during the pandemic (January 2020–March 2020) eras, and survived their index STEMI admission. The follow-up period was 1 year. One-year primary safety endpoint was all-cause mortality. Secondary safety endpoints were cardiac readmissions for unplanned revascularisation, non-fatal myocardial infarction, heart failure, arrythmia, unstable angina. Major adverse cardiovascular events (MACE) was defined as the composite outcome of each individual safety endpoint.Results: Despite unfavorable in-hospital outcomes among patients admitted during the pandemic compared to pre-pandemic era, both groups had similar 1-year all-cause mortality (11.2 vs. 8.5%, respectively, p = 0.454) but higher cardiac-related (14.1 vs. 5.1%, p < 0.001) and heart failure readmissions in the pandemic vs. pre-pandemic groups (7.1 vs. 1.7%, p = 0.037). Follow-up was more frequently conducted via teleconsultations (1.2 vs. 0.2 per patient/year, p = 0.001), with reduction in physical consultations (2.1 vs. 2.6 per patient/year, p = 0.043), during the pandemic vs. pre-pandemic era. Majority achieved guideline-directed medical therapy (GDMT) during pandemic vs. pre-pandemic era (75.9 vs. 61.6%, p = 0.010). Multivariable Cox regression demonstrated achieving medication target doses (HR 0.387, 95% CI 0.164–0.915, p = 0.031) and GDMT (HR 0.271, 95% CI 0.134–0.548, p < 0.001) were independent predictors of lower 1-year MACE after adjustment.Conclusion: The pandemic has led to the wider application of teleconsultation, with increased adherence to GDMT, enhanced medication target dosing. Achieving GDMT was associated with favorable long-term prognosis.

Correlation between fluoroscopy and tomographic aortic-root measurements in the decision of the transcatheter heart valve size in patients undergoing transcatheter aortic valve implantation

Abstract Introduction and hypothesis Transcatheter aortic valve implantation (TAVI) has become the standard treatment in intermediate and high-risk patients with high degree aortic stenosis (AS).(1–2) These has been also extended to low-risk and younger patients.(3–5) Besides the use of computed-tomography (CT) as diagnostic method to measure the aortic anatomy for transcatheter heart valve (THV) size decision and the radiation exposure (RE) during TAVI, younger patients are more exposed to radiation and contrast media (CM) complications due to a potentially second procedure.(6) Reducing RE and CM using only angiography aortic measurement could reduce the risk of RE and CM related complications without compromising the efficacy of the THV. We hypothesize that angiographic aortic root (AR) measure has good correlation with CT measure without compromising safety and efficacy of the THV. Methods Observational analysis: 1250 transfemoral TAVI patients with balloon or self-expandable valves were included. Aortic root CT measurement was done in all patients. AR measurement using Follow the right cup rule (7) was additionally done in 505 patients. Correlation between CT only (Group I n=745) versus CT and AR measurement (Group II n=505) was done. An inter and intraobserver validation analysis was done. Primary endpoint was VARC-2 device success. Secondary safety endpoints were composite of in-hospital and 30-days complications. Results Really good intra (0.86, p&amp;lt;0.001) and interobserver (0.81, p&amp;lt;0.001) correlation between CT (mean aortic diameter, distance between non (NC-HP) and left cusp hinge points (LC-HP) distance) and angiographic (LC-HP distance) measurements was observed. CT and AR measurement had a very good correlation between the two groups (CT mean aortic diameter vs CT NC-HP and LC-HP distance, 0.724 p&amp;lt;0.001; CT NC-HP and LC-HP distance vs angiographic NC-HP and LC-HP distance manual calibration 0.808 p&amp;lt;0.001; angiographic NC-HP and LC-HP distance manual calibration vs angiographic NC-HP and LC-HP distance automatic calibration 0.930 p&amp;lt;0.001). No differences in primary endpoint were observed between groups (device success Group I 98% vs Group II 99%, p 0.18). In-hospital complications were similar between two groups except in major bleeding (13% vs 19%, p 0.004), major vascular (10.9% vs 16.6%, p 0.004) and minor vascular (14% vs 21%, p 0.001) between group I and II respectively. Valve safety (86% vs 77%, p&amp;lt;0.001, OR 0.89, 95% CI 0.85–0.95) and clinical efficacy (84% vs 60.8%, p&amp;lt;0.001, OR 0.72, 95% CI 0.67–0.77) at 30 days were more common in group II. No difference in valve dysfunction was observed (Group I 10.3% vs Group II 7.3%, p 0.042, OR 1.41, 95% CI 0.97–2.05). Conclusions Compared to CT, AR measurement is a good option selecting THV size. No differences regarding device success and in-hospital and 30 days follow-up complications were observed. AR measurement could replace CT in specific cases. Funding Acknowledgement Type of funding sources: None. Angiographic and CT measurementsEndpoints

ADP-receptor antagonists in patients with acute myocardial infarction complicated by cardiogenic shock: a pooled IABP-SHOCK II and CULPRIT-SHOCK trial sub-analysis

Abstract Purpose The purpose of this pooled analysis is to compare the clinical outcome of patients with acute myocardial infarction complicated by cardiogenic shock treated with either clopidogrel or the newer, more potent ADP-receptor antagonists prasugrel or ticagrelor. Patients from the Intraaortic Balloon Pump in Cardiogenic Shock II (IABP-SHOCK II) and Culprit Lesion Only PCI versus Multivessel PCI in Cardiogenic Shock (CULPRIT-SHOCK) trial were included. Methods and results For the current analysis, the primary endpoint was 1-year mortality and the secondary safety endpoint was moderate or severe bleedings until hospital discharge with respect to three different ADP-receptor antagonists. Eight hundred fifty-six patients were eligible for analysis. Of these, five hundred seven patients (59.2%) received clopidogrel, one hundred seventy-eight patients (20.8%) prasugrel and one hundred seventy-one patients (20.0%) ticagrelor as acute antiplatelet therapy. The adjusted rate of mortality after 1-year did not differ between prasugrel and clopidogrel (hazard ratio [HR]: 0.81, 95% confidence interval [CI] 0.60–1.09, padj=0.17) or between ticagrelor and clopidogrel treated patients (HR: 0.86, 95% CI 0.65–1.15, padj=0.31). In-hospital bleeding events were significantly less frequent in patients treated with ticagrelor vs. clopidogrel (HR: 0.37, 95% CI 0.20–0.69, padj=0.002) and not different in patients treated with prasugrel vs. clopidogrel (HR: 0.73, 95% CI 0.43–1.24, padj=0.24), see Table 1. Conclusion This pooled sub-analysis is the largest analysis on safety and efficacy of three oral ADP-receptor antagonists and shows that an acute therapy with either clopidogrel, prasugrel or ticagrelor is no predictor of 1-year mortality. Treatment with ticagrelor seems to be associated with less in-hospital moderate and severe bleeding events in comparison to clopidogrel. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): German Heart FoundationEuropean Union 7th Framework Program

Thrombectomy in Extensive Stroke May Not Be Beneficial and Is Associated With Increased Risk for Hemorrhage

This study evaluates the benefit of endovascular treatment (EVT) for patients with extensive baseline stroke compared with best medical treatment. This retrospective, multicenter study compares EVT and best medical treatment for computed tomography (CT)–based selection of patients with extensive baseline infarcts (Alberta Stroke Program Early CT Score ≤5) attributed to anterior circulation stroke. Patients were selected from the German Stroke Registry and 3 tertiary stroke centers. Primary functional end points were rates of good (modified Rankin Scale score of ≤3) and very poor outcome (modified Rankin Scale score of ≥5) at 90 days. Secondary safety end point was the occurrence of symptomatic intracerebral hemorrhage. Angiographic outcome was evaluated with the modified Thrombolysis in Cerebral Infarction Scale. After 1:1 pair matching, a total of 248 patients were compared by treatment arm. Good functional outcome was observed in 27.4% in the EVT group, and in 25% in the best medical treatment group (P=0.665). Advanced age (adjusted odds ratio, 1.08 [95% CI, 1.05–1.10], P<0.001) and symptomatic intracerebral hemorrhage (adjusted odds ratio, 6.35 [95% CI, 2.08–19.35], P<0.001) were independently associated with very poor outcome. Mortality (43.5% versus 28.9%, P=0.025) and symptomatic intracerebral hemorrhage (16.1% versus 5.6%, P=0.008) were significantly higher in the EVT group. The lowest rates of good functional outcome (≈15%) were observed in groups of failed and partial recanalization (modified Thrombolysis in Cerebral Infarction Scale score of 0/1–2a), whereas patients with complete recanalization (modified Thrombolysis in Cerebral Infarction Scale score of 3) with recanalization attempts ≤2 benefitted the most (modified Rankin Scale score of ≤3:42.3%, P=0.074) compared with best medical treatment. In daily clinical practice, EVT for CT–based selected patients with low Alberta Stroke Program Early CT Score anterior circulation stroke may not be beneficial and is associated with increased risk for hemorrhage and mortality, especially in the elderly. However, first- or second-pass complete recanalization seems to reveal a clinical benefit of EVT highlighting the vulnerability of the low Alberta Stroke Program Early CT Score subgroup. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03356392.

IncobotulinumtoxinA Demonstrates Safety and Prolonged Duration of Effect in a Dose-Ranging Study for Glabellar Lines.

To further explore clinical trial results indicating increasing doses of botulinum toxin A prolong duration of effect, a 2-stage, phase 2, randomized, double-blind study investigated the duration of effect and safety of incobotulinumtoxinA (INCO; Xeomin&reg;, Bocouture&reg;) doses higher than the US Food and Drug Administration-approved 20 units (U) for glabellar frown lines (GFL). The stage 1 primary efficacy and safety results were reported previously. Here, we report the results of the final analysis (stage 1 and 2), including primary and secondary efficacy and safety endpoints. A total of 241 subjects with moderate-to-severe GFL were randomized to receive a single treatment with 20 (N=61), 50 (N=60), 75 (N=61), or 100U (N=59) INCO. The primary efficacy endpoint was duration of &ge; 1-point improvement from baseline assessed by investigator at maximum frown on the Facial Wrinkle Scale. The median duration of effect was 175 days for the 20U group (95% CI 142, 185), 185 days for the 50U group (95% CI 182, 205), 210 days for the 75U group (95% CI 182, 217), and 215 days for the 100U group (95% CI 183, 237). The incidence of treatment-related adverse events was low across all doses and there were no treatment-related serious adverse events. These results demonstrate that all INCO doses were well tolerated, consistent with the known safety profile of 20U, and increasing dose prolongs the duration of effect for GFL. J Drugs Dermatol. 2021;20(10):1052-1060. doi:10.36849/JDD.6377THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL TEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.

Efficacy and Safety of Ticagrelor Monotherapy by Clinical Presentation: Pre-Specified Analysis of the GLOBAL LEADERS Trial.

BackgroundThe optimal duration of dual antiplatelet therapy after coronary drug‐eluting stent placement in adults with stable coronary artery disease (SCAD) versus acute coronary syndromes (ACS) remains uncertain.Methods and ResultsThis was a prespecified subgroup analysis of the GLOBAL LEADERS trial. Participants were randomly assigned 1:1 to the experimental or reference strategy, stratified by ACS (experimental, n=3750; reference, n=3737) versus SCAD (experimental, n=4230; reference, n=4251). The experimental strategy was 75 to 100 mg aspirin daily plus 90 mg ticagrelor twice daily for 1 month, followed by 23 months of ticagrelor monotherapy. The reference strategy was 75 to 100 mg aspirin daily plus either 75 mg clopidogrel daily (for SCAD) or 90 mg ticagrelor twice daily (for ACS) for 12 months, followed by aspirin monotherapy for 12 months. The primary end point at 2 years was a composite of all‐cause mortality or non‐fatal centrally adjudicated new Q‐wave myocardial infarction. The key secondary safety end point was site‐reported Bleeding Academic Research Consortium grade 3 or 5 bleeding. The primary end point occurred in 147 (3.92%) versus 169 (4.52%) patients with ACS (rate ratio [RR], 0.86; 95% CI, 0.69–1.08; P=0.189), and in 157 (3.71%) versus 180 (4.23%) patients with SCAD (RR, 0.87; 95% CI, 0.71–1.08; P=0.221) with experimental and reference strategy, respectively (P‐interaction=0.926). Bleeding Academic Research Consortium grade 3 or 5 bleeding occurred in 73 (1.95%) versus 100 (2.68%) patients with ACS (RR, 0.73; 95% CI, 0.54–0.98; P=0.037), and in 90 (2.13%) versus 69 (1.62%) patients with SCAD (RR, 1.32; 95% CI, 0.97–1.81; P=0.081; P‐interaction=0.007).ConclusionsWhile there was no evidence for differences in efficacy between treatment strategies by subgroup, the experimental strategy appeared to reduce bleeding risk in patients with ACS but not in patients with SCAD.RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT01813435.

Outcomes of Spironolactone Withdrawal in Dilated Cardiomyopathy With Improved Ejection Fraction.

Background: The feasibility of spironolactone withdrawal in dilated cardiomyopathy patients with improved ejection fraction remains unknown. This study sought to determine whether spironolactone can be withdrawn safely in this circumstance.Methods: Consecutive patients with idiopathic dilated cardiomyopathy and prescribed spironolactone at discharge were included in this prospective, observational cohort using the Risk Evaluation and Management in Heart Failure Trial (NCT02998788) database. Those patients who experienced an absolute left ventricular ejection fraction (LVEF) improvement ≥10% and a second measurement of LVEF >40% would choose whether to continue spironolactone therapy and be included in final analysis. The primary endpoint was dilated cardiomyopathy relapse within 12 months, defined as a more than 10% reduction in LVEF, a 15% or greater increase in LVESVi, a 2-fold rise in NT-proBNP, or clinical signs of heart failure.Results: Seventy patients achieved an ejection fraction improvement and were included in the final analysis, of whom 30 chose to continue spironolactone and 40 decided to withdraw. In primary endpoint analysis, 23 (58%) patients from the withdrawal group and 4 (13%) patients from the continuation group relapsed (relative risk for relapse: 4.31; 95% CI: 1.67–11.11; p < 0.001). Patients from the withdrawal group experienced more symptom aggravation than the continuation group. No secondary safety endpoint was recorded. Improvements in cardiac structure parameters were no longer observed after spironolactone withdrawal, while improvements persisted in continuation group.Conclusions: Most dilated cardiomyopathy patients with improved ejection fraction will relapse after spironolactone withdrawal. These results should be weighed before spironolactone withdrawal was attempted.

Ticagrelor or Prasugrel in Patients With Acute Coronary Syndrome in Relation to EstimatedGlomerular Filtration Rate.

The aim of this study was to assess the safety and efficacy of ticagrelor versus prasugrel for patients with acute coronary syndrome (ACS) according to their estimated glomerular filtration rates (eGFRs). The outcomes of ticagrelor versus prasugrel in patients with ACS according to eGFR have not been defined. Patients (n=4,012) were categorized into 3 groups: low eGFR (<60mL/min/1.73m2), intermediate eGFR (≥60 and<90mL/min/1.73m2), and high eGFR (≥90mL/min/1.73m2). The primary endpoint was a composite of all-cause death, myocardial infarction, and stroke; the secondary safety endpoint was Bleeding Academic Research Consortium types 3 to 5 bleeding, both at 1 year. Patients with low eGFRs had a higher risk for the primary endpoint compared with patients with intermediate eGFRs (adjusted HR: 1.89; 95% CI: 1.46-2.46]) and those with high eGFRs (adjusted HR: 2.33; 95%CI: 1.57-3.46). A risk excess for low eGFR was also observed for bleeding (adjusted HR: 1.55 [95%CI: 1.12-2.13] vs intermediate eGFR; adjusted HR: 1.59 [95%CI: 1.01-2.50] vs high eGFR). However, eGFR did not affect the relative efficacy and safety of ticagrelor versus prasugrel. In patients with low eGFR, the primary endpoint occurred in 20.5% with ticagrelor and in 14.7% with prasugrel (HR: 1.47; 95%CI: 1.04-2.08; P=0.029); there was no significant difference in bleeding. These results show that among patients with ACS, reduction of eGFR is associated with increased risk for ischemic and bleeding events but has no significant impact on the relative efficacy and safety of ticagrelor versus prasugrel. (Prospective, Randomized Trial of Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome [ISAR-REACT 5]; NCT01944800).

Efficacy and Cardiovascular Safety of Roxadustat for Treatment of Anemia in Patients with Non-Dialysis-Dependent CKD: Pooled Results of Three Randomized Clinical Trials.

We evaluated the efficacy and cardiovascular safety of roxadustat versus placebo by analyzing data pooled from three phase 3 studies of roxadustat in patients with non-dialysis-dependent CKD and CKD-related anemia. In the three phase 3, double-blind studies of roxadustat versus placebo evaluating the treatment of CKD-related anemia in patients not requiring dialysis, the primary efficacy end point was mean change from baseline in hemoglobin averaged over weeks 28-52, regardless of rescue therapy. The primary cardiovascular safety end point was a composite measure of major adverse cardiovascular events (MACE; all-cause mortality, myocardial infarction, stroke). MACE plus (MACE+; MACE plus unstable angina and heart failure requiring hospitalization) and all-cause mortality were key secondary safety end points. These safety end points were adjudicated. A total of 4277 patients with non-dialysis-dependent CKD were randomized (roxadustat, n=2391; placebo, n=1886). Baseline characteristics were comparable between groups; the mean (SD) hemoglobin was 9.1 (0.7) g/dl and mean eGFR was 20 (12) ml/min per 1.73 m2. Patients treated with roxadustat versus those treated with placebo showed a mean change from baseline in hemoglobin averaged over weeks 28-52, regardless of rescue therapy, of 1.9 versus 0.2 g/dl, a treatment difference of 1.7 (95% confidence interval [95% CI], 1.7 to 1.8). Roxadustat reduced the need for red blood cell transfusion in the first 52 weeks versus placebo (6.1 versus 20.4 per 100 patient-exposure years, respectively; hazard ratio [HR], 0.26; 95% CI, 0.21 to 0.32). There were no increased risks of MACE (HR, 1.10; 95% CI, 0.96 to 1.27), MACE+ (HR, 1.07; 95% CI, 0.94 to 1.21), all-cause mortality (HR, 1.08; 95% CI, 0.93 to 1.26), or individual MACE+ components in patients treated with roxadustat versus those treated with placebo. Roxadustat was more effective than placebo at increasing hemoglobin in patients with non-dialysis-dependent CKD and anemia, while decreasing transfusion rate and being noninferior to placebo with respect to risk of MACE. A Study of FG-4592 for the Treatment of Anemia in Chronic Kidney Disease Patients Not Receiving Dialysis, NCT01750190; Roxadustat in the Treatment of Anemia in Chronic Kidney Disease Patients Not Requiring Dialysis (ALPS), NCT01887600; Safety and Efficacy Study of Roxadustat to Treat Anemia in Patients With Chronic Kidney Disease (CKD), Not on Dialysis, NCT02174627.

Anticoagulation for the Treatment of Acute Venous Thromboembolism a Systematic Review and Network Meta-Analysis

Background: There are several anticoagulation strategies are suggested for patients with acute venous thromboembolism (VTE), however proof, especially for cancer-associated VTE, is lacking of which strategy is optimal choice. We aimed to compare efficacy and safety outcomes among various anticoagulation strategies for patients with VTE using a systematic review and network meta-analysis. Methods: A systematic literature search was conducted using PUBMED, EMBASE, and Cochrane Library Central Register of Controlled Trials and clinical trial registries from inception through June 1, 2021. We search for randomized clinical trials (RCTs) comparing the recurrent VTE and bleeding outcomes of various anticoagulation strategies (low-molecular-weight heparin (LMWH), unfractionated heparin (UFH), or fondaparinux combined with vitamin K antagonists(VKA)); direct oral anticoagulants) for patients with acute VTE(noncancer or cancer-associated). Extraction of clinical outcomes were performed independently by two authors. A Bayesian network meta-analysis was applied to analyze the data. The primary efficacy endpoint was recurrent VTE episodes, the primary safety endpoint was major bleeding episodes. Secondary efficacy endpoints were fatal recurrent venous thromboembolism, the secondary safety endpoints were fatal bleeding episodes, all-cause mortality and major gastrointestinal bleeding. Results: 12117 citations were identified, 9850 unique citations, 54 RCTs met the inclusion criteria. Included trials recruited 49952 VTE participants with cancer or non-cancer. The findings showed that UFH-VKA likely increases recurrent VTE compared to LMWH-VKA (hazard ratio ((HR) 1·44(1·16,1·80), apixaban was probably the most effective strategy (surface under the cumulative ranking curve (SUCRA) 87·6%). Subgroup analysis for VTE patients with cancer shown that LMWH (HR 0·61(0·40,0·89)) and apixaban (HR 0·40(0·21,0·66)) were associated with less recurrent VTE events compared with LMWH-VKA. Apixaban (HR 0·44(0·24,0·73)) lowered the rate of major bleeding compared with the LMWH–VKA. The apixaban was probably the safest strategy (SUCRA 96·5%). For patients with cancer-associated acute VTE, although apixaban group experienced less major bleeding events compared with LMWH-VKA, it was not statically significant (HR 0·80(0·36,1·55)). Interpretation: Apixaban seems to be superior to other anticoagulation strategies for treatment of VTE with cancer. Funding: This work received research grant from The Second Hospital of Anhui Medical University(Hefei, Anhui 230601, China). Grant number: LBSART202007. Declaration of Interest: None to declare.

Randomized, Double-Blind Trial of Ferumoxytol Compared to Ferric Carboxymaltose for Treatment of Iron Deficiency Anemia: Safety and Efficacy

Background: Intravenous (IV) iron is often used to treat iron deficiency anemia (IDA) in patients unresponsive to, or intolerant of, oral iron. IV iron has been associated with rare, but potentially serious acute hypersensitivity reactions (HSRs). The few randomized trials which assessed comparative risks of adverse events (AEs) with IV iron formulations are limited by small numbers and lack statistical power to identify differences in low frequency AEs such as HSRs. We have attempted to correct this deficit in the literature, by conducting a randomized double-blind clinical trial comparing two IV iron preparations.Aims: To evaluate the comparative safety and efficacy of standard courses of two IV iron preparations, ferumoxytol and ferric carboxymaltose (FCM), with the primary endpoint being the combined incidence of moderate to severe HSRs, including anaphylaxis, or moderate to severe hypotension. A secondary safety endpoint was the composite incidence of moderate to severe HSRs, including anaphylaxis, serious cardiovascular events, or death. Efficacy endpoints included change from baseline in hemoglobin (Hb) and change in Hb per gram of iron administered.Methods: This randomized, double-blind, international, multicenter, trial (NCT02694978) included adults with IDA of any etiology excluding dialysis-dependent CKD (Hb <12.0 g/dL for females; <14.0 g/dL for males and transferrin saturation ≤20% or ferritin ≤100 ng/mL within 60 days of dosing) and a history of unsatisfactory response to or intolerance of oral iron. Randomization was 1:1 to ferumoxytol, administered as two 510 mg doses, or FCM, administered as two 750 mg doses both delivered as an IV infusion over at least 15 minutes on days 1 and 8. Patients were observed for at least 1 hour following the infusions. Follow-up visits were conducted at weeks 2 and 5. All events suggesting possible hypersensitivity or hypotension were reviewed and adjudicated by an expert, independent, blinded Clinical Events Committee (CEC) utilizing pre-specified criteria per protocol. All participants provided written informed consent before enrollment.Results: 2014 patients were randomized at 129 sites in North America (US and Canada) and Eastern Europe (Latvia, Lithuania, Poland, and Hungary). The safety population included the 1997 randomized patients who received any amount of study drug (mean age 55.2 ±17.2 years, 76.1% female, mean baseline values: Hb 10.4 g/dL, transferrin saturation 13.9%, serum ferritin 57.4 ng/mL). The most common underlying causes of IDA included: chronic kidney disease (27%), abnormal uterine bleeding (25%) and gastrointestinal disorders (29%). Ferumoxytol demonstrated non-inferiority (NI) to FCM with respect to both the primary (ferumoxytol rate: 0.6%; FCM rate: 0.7%; treatment difference: -0.1% ; 95% confidence interval: -0.80% to +0.61%) and secondary safety endpoints (ferumoxytol rate: 1.3%; FCM rate: 2.0%; treatment difference: -0.7% ; 95% confidence interval: -1.81% to +0.42%) [TABLE]. Ferumoxytol demonstrated non-inferiority to FCM for both secondary efficacy endpoints (mean change in Hb from Baseline to Week 5, and mean change in Hb from Baseline to Week 5 per gram of iron administered), while additionally demonstrating a significantly greater increase in Hb per gram of iron administered [FIGURE]. Median increase from Baseline to Week 5 in serum ferritin was 182.2 ng/mL for ferumoxytol and 320.5 ng/mL for FCM.Conclusion: While there is little debate as to the efficacy of IV irons on increasing hemoglobin concentrations in patients with IDA, the occurrence of rare but potentially serious acute HSRs continues to be a focus of concern. Very few well conducted trials have compared two or more IV iron formulations by evaluating HSR and hypotension as primary endpoints. In this study there was no significant difference between FCM and ferumoxytol in the composite endpoints of moderate to severe HSR, including anaphylaxis, or moderate to severe hypotension, serious cardiovascular events or all-cause mortality. [Display omitted] DisclosuresAuerbach:AMAG Pharma, Pharmacosmos, Luitpold: Consultancy; AMAG Pharma, Pharmacosmos: Research Funding. Strauss:AMAG pharmaceuticals: Employment, Equity Ownership. Macdougall:AMAG: Consultancy, Honoraria, Research Funding; Pharmacosmos: Honoraria; Vifor Pharma: Consultancy, Honoraria, Research Funding, Speakers Bureau; Akebia: Consultancy; GlaxoSmithKline: Consultancy; Astellas: Honoraria, Research Funding; FibroGen: Consultancy, Speakers Bureau. Bernard:AMAG: Employment. Kaper:AMAG Pharmaceuticals, Inc.: Employment. Chertow:AMAG: Consultancy; Akebia: Consultancy; Amgen: Consultancy, Research Funding; Keryx: Consultancy. Li:AMAG Pharmaceuticals: Employment, Equity Ownership. Trochanov:AMAG Pharmaceutical,Inc: Employment, Other: Company stock. Dahl:AMAG Pharmaceuticals. Inc.: Employment, Equity Ownership. Krop:AMAG Pharmaceuticals: Employment, Other: Stock in company.

Safety and Efficacy of Different Antithrombotic Strategies after Transcatheter Aortic Valve Implantation: A Network Meta-Analysis.

The optimal pharmacological therapy after transcatheter aortic valve implantation (TAVI) remains uncertain. We compared efficacy and safety of various antiplatelet and anticoagulant approaches after TAVI by a network meta-analysis. A total of 14 studies (both observational and randomized) were considered, with 24,119 patients included. Primary safety endpoint was the incidence of any bleeding complications during follow-up. Secondary safety endpoint was major bleeding. Efficacy endpoints were stroke, myocardial infarction, and cardiovascular mortality. A frequentist network meta-analysis was conducted with a random-effects model. The following strategies were compared: dual antiplatelet therapy (DAPT), single antiplatelet therapy (SAPT), oral anticoagulation (OAC), and OAC + SAPT. The mean follow-up was 15 months. In comparison to DAPT, SAPT was associated with a 44% risk reduction of any bleeding (odds ratio [OR]: 0.56 [95% confidence interval, CI: 0.39-0.80]). SAPT was ranked as the safest strategy for the prevention of any bleeding (p-score: 0.704), followed by OAC alone (p-score: 0.476) and DAPT (p-score: 0.437). Consistent results were observed for major bleeding. The incidence of cardiovascular death and secondary ischemic endpoints did not differ among the tested antithrombotic approaches. In patients with indication for long-term anticoagulation, OAC alone showed similar rates of stroke (OR: 0.92 [95% CI: 0.41-2.05], p = 0.83) and reduced occurrence of any bleeding (OR: 0.49 [95% CI: 0.37-0.66], p < 0.01) versus OAC + SAPT. The present network meta-analysis supports after TAVI the use of SAPT in patients without indication for OAC and OAC alone in those needing long-term anticoagulation.

A meta-analysis on allergen-specific immunotherapy using MCT® (MicroCrystalline Tyrosine)-adsorbed allergoids in pollen allergic patients suffering from allergic rhinoconjunctivitis.

BackgroundThe World Allergy Organization and the European Academy of Allergy and Clinical Immunology recommend to perform product‐specific meta‐analyses for allergen‐specific immunotherapies because of the high degree of heterogeneity between individual products. This meta‐analysis evaluates the efficacy and safety of Glutaraldehyde‐modified and MCT® (MicroCrystalline Tyrosine)‐adsorbed allergoids (MATA).MethodsThe databases MEDLINE, LILACS, embase, LIVIVO, Web of Science and Google (Scholar) were searched for publications on MATA up to June 2019. Primary endpoint was the combined symptom and medication score (CSMS). Secondary endpoints were single scores, immunogenicity and improvement of allergic condition. Secondary safety endpoints were the occurrence of side effects. A random effects model was applied with (standardized) mean differences ([S]MDs) including confidence intervals (CI). Heterogeneity was analyzed using the I2 index and publication bias using Egger's test and Funnel plots. Subgroups were analyzed regarding age and asthma status.ResultsEight randomized double‐blind placebo‐controlled trials were selected for efficacy and 43 publications for safety analysis. In total, 4531 patients were included in this analysis including eight studies containing data on children and adolescents. AIT with MATA significantly reduced allergic symptoms and medication use with a SMD for CSMS of −0.8 (CI: −1.24, −0.36) in comparison to placebo. Heterogeneity was moderate between the studies. The total symptom score (−1.2 [CI: −2.11, −0.29]) and the total medication score (−2.2 [CI: −3.65, −0.74]) were also significantly reduced after MATA treatment. Patient's condition improved significantly after treatment with MATA, with an odds ratio of 3.05 (CI: 1.90, 4.90) when compared to placebo. The proportion of patients, who developed side effects was 38% (CI: 19%, 57%). No serious side effects occurred. Safety in the subgroups of asthmatic patients, children and adolescents did not differ from the overall patient population.ConclusionsThis meta‐analysis reveals a large body of evidence from publications investigating MATA. MATA significantly improved allergic symptoms and reduced the use of anti‐allergic medication in comparison to placebo, with an excellent safety profile. Especially for children and asthmatic patients, the use of MATAs can be considered as safe, because the safety profiles in these groups did not differ from the total patient population.

Sex-Based Differences in Autologous Cell Therapy Trials in Patients With Acute Myocardial Infarction: Subanalysis of the ACCRUE Database.

Background: Sex-based differences are under-studied in cardiovascular trials as women are commonly underrepresented in dual sex studies, even though major sex-based differences in epidemiology, pathophysiology, and outcomes of cardiovascular disease have been reported. We examined sex-based differences in patient characteristics, outcome, and BM-CD34+ frequency of the ACCRUE (Meta-Analysis of Cell-based CaRdiac studies) database involving patients with acute myocardial infarction (AMI) randomized to autologous cell-based or control treatment.Methods: We compared baseline characteristics and 1-year follow-up clinical data: composite major adverse cardiac and cerebrovascular events (primary endpoint), and changes in left ventricular ejection fraction (LVEF), end-diastolic (EDV), and end-systolic volumes (ESV) (secondary efficacy endpoint) in women and men (N = 1,252; 81.4% men). Secondary safety endpoints included freedom from hard clinical endpoints.Results: In cell-treated groups, women but not men had a lower frequency of stroke, AMI, and mortality than controls. The frequency of BM-CD34+ cells was significantly correlated with baseline EDV and ESV and negatively correlated with baseline LVEF in both sexes; a left shift in regression curve in women indicated a smaller EDV and ESV was associated with higher BM-CD34+ cells in women.Conclusions: Sex differences were found in baseline cardiovascular risk factors and cardiac function and in outcome responses to cell therapy.

Selective serotonin reuptake inhibitors for debilitating vasovagal syncope: looking for copper and finding gold

Abstract Funding Acknowledgements Type of funding sources: None. Background Despite its benign course, recurrent and unpredictable vasovagal syncope (VVS) may be disabling. Even though a non-pharmacological approach is generally regarded as first-line, a variety of drugs might also be of use. In this respect, the clinical value of selective serotonin reuptake inhibitors (SSRIs) is still a matter of debate. Purpose To perform a meta-analysis aimed at evaluating the extent to which SSRIs might reduce VVS recurrences in susceptible patients. Methods We systematically searched MEDLINE, Embase, Web of Science, Cochrane Library and Google Scholar for prospective studies, addressing the effect of SSRIs on the recurrence rate of VVS in predisposed patients, published up until December 31st, 2020. In order to be included in the quantitative analysis, studies were required to encompass a positive head-up tilt table (HUTT) test for VVS diagnosis and a minimum patient follow-up of 6 months. The primary endpoint was recurrent spontaneous VVS, whereas secondary endpoints included the efficacy outcome of HUTT test-induced VVS and the safety outcome of drug discontinuation for adverse effects. Randomized controlled trials (RCTs) and studies including the most represented SSRI drug were further investigated separately, with respect to the primary endpoint. Study-specific odds ratios (ORs) were pooled using traditional meta-analytic techniques, under a random-effects model. Results 3 RCTs (2 placebo-controlled and 1 both placebo- and active-controlled) and 1 non-randomized prospective study, encompassing 222 and 127 patients, respectively, were regarded as eligible for quantitative evaluation. Patient follow-up ranged between 6 and 24 months. 131 patients were allocated to the SSRI arm, which featured fluoxetine as the most represented element (97 cases). The absolute number of events for each outcome may be reported as follows: primary efficacy endpoint, 57; secondary efficacy endpoint, 68 (only 2 RCTs reporting); secondary safety endpoint, 4 (only 2 RCTs reporting). In the main analysis, SSRIs were not found to significantly reduce VVS recurrence rate (OR 0.48, 95% CI 0.13-1.81, P 0.28, i2 74%). This null result was, however, single-handedly driven by the only non-randomized study included (OR 4.5, 95% CI 0.85-23.8). Likewise, fluoxetine was not able to significantly reduce the primary efficacy endpoint (OR 0.7, 95% CI 0.12-4.12, P 0.7, i2 78%), while SSRIs only numerically cut HUTT test-induced VVS events (OR 0.66, 95% CI 0.24-1.84, P 0.43, i2 59%). Nevertheless, when only RCTs are considered, SSRIs exerted a meaningful reduction in VVS recurrence rate, with no heterogeneity (OR 0.25, 95% CI 0.12-0.5, P 0.0001, i2 0%). In addition, drug discontinuation for safety reasons was rare and comparable between the SSRI and the placebo arms (OR 1.51, 95% CI 0.21-10.74, P 0.59, i2 0%). Conclusion SSRIs do represent one more safe pharmacological option to reduce syncope recurrences in patients with otherwise refractory VVS. Abstract Figure.

Clopidogrel vs. prasugrel vs. ticagrelor in patients with acute myocardial infarction complicated by cardiogenic shock: a pooled IABP-SHOCK II and CULPRIT-SHOCK trial sub-analysis

AimsThe aim of this pooled sub-analysis of the Intraaortic Balloon Pump in Cardiogenic Shock II (IABP-SHOCK II) and Culprit Lesion Only PCI versus Multivessel PCI in Cardiogenic Shock (CULPRIT-SHOCK) trial was to compare the clinical outcome of patients with acute myocardial infarction complicated by cardiogenic shock treated either with clopidogrel or the newer, more potent ADP-receptor antagonists prasugrel or ticagrelor.Methods and resultsFor the current analysis the primary endpoint was 1-year mortality and the secondary safety endpoint was moderate or severe bleedings until hospital discharge with respect to three different ADP-receptor antagonists. 856 patients were eligible for analysis. Of these, 507 patients (59.2%) received clopidogrel, 178 patients (20.8%) prasugrel and 171 patients (20.0%) ticagrelor as acute antiplatelet therapy. The adjusted rate of mortality after 1-year did not differ significantly between prasugrel and clopidogrel (hazard ratio [HR]: 0.81, 95% confidence interval [CI] 0.60–1.09, padj = 0.17) or between ticagrelor and clopidogrel treated patients (HR: 0.86, 95% CI 0.65–1.15, padj = 0.31). In-hospital bleeding events were significantly less frequent in patients treated with ticagrelor vs. clopidogrel (HR: 0.37, 95% CI 0.20 -0.69, padj = 0.002) and not significantly different in patients treated with prasugrel vs. clopidogrel (HR: 0.73, 95% CI 0.43 -1.24, padj = 0.24).ConclusionThis pooled sub-analysis is the largest analysis on safety and efficacy of three oral ADP-receptor antagonists and shows that acute therapy with either clopidogrel, prasugrel or ticagrelor is no independent predictor of 1-year mortality. Treatment with ticagrelor seems independently associated with less in-hospital moderate and severe bleeding events compared to clopidogrel. This finding might be due to selection bias and should be interpreted with caution.Graphic abstract