Efficacy and Safety of Aspirin-free versus Aspirin-based Strategies in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis.

Introduction: Conventional PCI with stenting in high bleeding risk (HBR) patients is associated withhigher all-cause mortality rates and bleeding complications. To minimize DAPT duration, stentlessPCI using drug-coated balloons (DCB) is increasingly favored. However, there is a lack ofcomprehensive long-term outcome data on stentless therapy in HBR patients within real-worldclinical practice. Research Questions: Do discernible disparities exist in the extended-term ramifications of stentless treatment utilizing DCB between patients classified as having HBR and those without in clinical practice? Methods: We incorporated patients who underwent stentless PCI employing DCB for de novo lesions at our medical facility from January 2015 to December 2021. Exclusion criteria encompassedpatients presenting with acute coronary syndromes. The primary outcome measure was defined as all-cause mortality, whereas the secondary outcome measure focused on bleeding events as per thedefined criteria of BARC bleeding grades 3 or 5. Patients were stratified into two cohorts based on the ARC-HBR criteria and subsequently subjected to comparative analysis utilizing Cox proportional hazards regression analysis. Results: A total of 392 patients were included, including a mean age of 70 ± 11 years and 46% male. Of these patients, 62% had HBR, and the procedure's success rate was 99.7%. Over a median follow-up period of 24 months, 29 patients (7.4%) experienced all-cause mortality. HBR patients showed significantly higher blood BNP levels compared to non-HBR patients (median [IQR]: 85pg/mL [36-226] vs. 27 pg/mL [15-49], p<0.01). After adjusting for blood BNP levels, the hazard ratio for all-cause mortality in HBR patients was 4.06 [1.18-14.00], indicating a 4-fold higher risk compared to non-HBR patients (p=0.03). Among the cohort, 12 individuals (1.8%) experienced BARC grades 3 or 5 bleeding events, with a tendency towards a greater occurrence in the HBRpatient group (adjusted HR: 2.26 [0.46-11.20], p=0.32), although the difference was not significant. Conclusions: The findings further indicate that patients with HBR exhibit a propensity for inferior long-term outcomes relative to non-HBR patients in stentless treatment with DCB in the real world.

The management of high bleeding risk (HBR) patients with an acute coronary syndrome (ACS) who undergo percutaneous coronary intervention (PCI) is challenging because these patients combine a severe thrombotic burden with a significant risk of bleeding complications. The aim of this study was to quantify the prevalence of HBR patients in a real-world ACS population, identify their in-hospital prognosis, and record their bleeding complications compared to non-HBR patients. In this real-world registry, patients with an ACS who had undergone successful revascularization with PCI were classified into HBR and non-HBR based on the Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria and were monitored during their hospitalization. A total of 314 patients were enrolled: 103 HBR (32.8%) and 211 (67.2%) non-HBR. In-hospital all-cause mortality (17.4% vs. 2.84%, p < 0.001), cardiovascular mortality (12.6% vs. 2.84%, p < 0.001) and major bleeding events (15.5% vs. 1.89%, p < 0.001) were significantly higher in the HBR group. The trans-femoral access during PCI (OR = 3.524, 95% CI: 1.035-11.991, p = 0.044) and the baseline estimated glomerular filtration rate (eGFR) (OR = 0.966, 95% CI: 0.938-0.996, p = 0.027) were the only independent predictors of severe bleeding. More specifically, an e-GFR value ≤ 50 ml/min was calculated to predict in-hospital major bleeding complications in HBR patients with 87.5% sensitivity and 64.37% specificity. In-hospital all-cause mortality, cardiovascular mortality, and major bleeding events were significantly higher in HBR patients with an ACS compared to non-HBR patients. HBR patients with baseline impaired renal function should be carefully monitored for severe bleeding complications.

High bleeding risk patients with acute coronary syndromes treated with contemporary drug-eluting stents and Clopidogrel or Ticagrelor: Insights from CHANGE DAPT

Introduction Current clinical guidelines recommend prolonged dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI) in patients presenting with acute coronary syndromes (ACS). However, an extended DAPT duration in high-bleeding risk (HBR) patients amplifies the risk of post procedural complications. Hence, clinicians often face the dilemma of prolonging DAPT duration to prevent recurrent ischaemic events at the expense of increasing the incidence of bleeding in high-risk patients. The actual incidence of ischaemic and bleeding events in this particular population is not well elucidated. Purpose To evaluate one-year ischemic and bleeding outcomes following PCI for ACS in a real-world HBR population as defined by the Academic Research Consortium (ARC) consensus document. Methods We included all patients who presented with ACS to a high-volume single PCI centre from 2012 to 2017 and underwent PCI with 2nd generation drug-eluting stent implantation. Patients were classified as HBR if they met ≥1 major or ≥2 minor criteria according to the recent ARC-HBR consensus. The outcomes of interest were major adverse cardiovascular events (MACE), a composite of all-cause death, myocardial infarction (MI), and target lesion revascularization (TLR), and major bleeding events, including both peri-procedural and post-discharge bleeding. All outcomes were assessed at 1-year follow-up. The Kaplan-Meier method was used for time-to-event analyses. Results Out of 6,097 ACS patients included in this analysis, 2,717 (44.6%) fulfilled the ARC-HBR definition. Compared to non-HBR group, HBR patients were more frequently female, older, more likely to have cardiovascular risk factors (e.g., diabetes, hypertension, and hyperlipidemia) and complex coronary artery disease (e.g., multi-vessel disease, bifurcation lesions, and calcification). The 1-year incidence of MACE was significantly higher in HBR patients (16.3% vs. 8.1%, HR 2.16, 95% CI [1.81–2.59], p&amp;lt;0.001) (Figure 1A). This finding was driven by higher rates of all-cause death and MI (Figure 1B). The 1-year incidence of major bleeding was also significantly higher in HBR patients compared to non-HBR (11.1% vs. 3.1%, HR: 3.92, 95% CI 3.10–4.95; p&amp;lt;0.001). Conclusions HBR patients undergoing PCI for ACS are not only subject to bleeding complications but are also at an increased risk for ischemic events and all-cause mortality. Figure 1 Funding Acknowledgement Type of funding source: None

Coronary artery disease (CAD) is one of the leading causes of death in our patient population. In the era of cardiovascular intervention, Percutaneous coronary intervention (PCI) is one of the most important modalities in treating these group of patients. Several CAD risks factors and co-morbid conditions are key responsible factor of procedural success. High bleeding risk (HBR) patients undergoing PCI is not an uncommon phenomenon. Incidences and prevalence of HBR patients with CAD and their management by PCI is not well addressed in our literature. PCI in HBR patients carries potential risk of intracranial hemorrhage (ICH) and lifethreatening bleeding. Therefore, careful pre-PCI assessment of possible risk or threats of post-PCI complications in patients with HBR are deem necessitate to understand. We recommend forming multicenter common consensus and to form a guideline in treating HBR patient by PCI. Thus, to reduce post procedural complication and subsequent improvement of mortality and morbidity in HBR patients undergoing PCI in both ST segment elevated myocardial infarction (STEMI) and as well as non-STEMI. Bangladesh Heart Journal 2021; 36(2): 133-138

ObjectivesIn an all-comers cohort undergoing percutaneous coronary intervention (PCI), we aimed to assess prevalence of high bleeding risk (HBR) patients and impact of HBR and dual antiplatelet therapy (DAPT) on clinical events. BackgroundHBR represents a complex subgroup of patients undergoing PCI. MethodsIn the ReCre8 trial, patients undergoing PCI were stratified for troponin status and diabetes and randomized to a permanent polymer zotarolimus-eluting- or polymer-free amphilimus-eluting stent. Patients were treated with 12 months (troponin-positive) or one month (troponin-negative) of DAPT. We evaluated clinical outcomes in patients with and without HBR according to the Academic Research Consortium for High Bleeding Risk criteria. ResultsFrom a total of 1488 patients included in this subanalysis, 406 patients (27.3 %) were identified as being at HBR. Among HBR patients, target-lesion failure (TLF) was similar after one year yet was higher after three years (13.3 % vs. 9.1 %; p = 0.013), compared to non-HBR patients. There was no difference in Bleeding Academic Research Consortium (BARC) 3 to 5 bleeding, however BARC 2 to 5 bleeding was higher after three years with 4.9 % vs. 3.0 % (p = 0.037). There were no differences between troponin-positive (12-months DAPT) and -negative (1-month DAPT) HBR patients with respect to ischemic and bleeding outcomes. ConclusionsIn this all-comers population of PCI patients, a higher TLF rate among HBR patients at long-term follow-up was found, underlining the complexities involving treatment of HBR patients. We did not observe statistically significant differences in BARC 3 to 5 bleeding between HBR and non-HBR patients regardless of DAPT duration. Clinical trial registrationURL: http://www.clinicaltrials.gov, unique identifier: NCT02328898.

BackgroundTo date, it has not been ascertained whether shortening the duration of dual antiplatelet therapy (DAPT) can benefit high bleeding risk (HBR) patients. This systematic review and meta-analysis was performed to investigate the safety and efficacy of short (≤ 3 months) DAPT in HBR patients after percutaneous coronary intervention (PCI).MethodsThe PubMed, Embase, and Clinical Trials databases were searched from inception until November 2021 to identify studies that evaluated the safety and efficacy of short DAPT in HBR patients implanted with new-generation drug-eluting stents (DES). Primary endpoints included major bleeding, definite or probable stent thrombosis (ST), and myocardial infarction (MI), while secondary endpoints included all-cause death and ischemic stroke. Based on the fixed and random effect model, the risk ratio (RR) and 95% confidence interval of each endpoint were measured.ResultsFive observational studies and one randomized controlled trial were included, involving 15,432 HBR patients. Short DAPT for HBR patients undergoing PCI had a lower incidence of major bleeding in comparison with standard (> 3 months) DAPT (2.3% vs. 3.2%, RR 0.64 [0.44, 0.95], p = 0.03), while short DAPT was comparable to standard DAPT with regard to definite or probable ST (0.4% vs. 0.3%, RR 1.31 [0.77, 2.23], p = 0.32) and MI (2.4% vs. 2.0%, RR 1.17 [0.95, 1.45], p = 0.14).ConclusionsAmong HBR patients implanted with new-generation DES, short DAPT was associated with reduced risk of major bleeding without significantly increasing the risk of definite or probable ST and MI in comparison with standard DAPT.

Data on ischemic and bleeding outcomes after percutaneous coronary intervention (PCI) in high bleeding risk (HBR) patients with chronic kidney disease (CKD) are scarce. We aimed to evaluate the association between CKD and ischemic and bleeding outcomes in HBR patients who underwent PCI. Among 10,502 patients in the four post-approval registries evaluating patients undergoing PCI, 2,300 patients presented with at least one major or two minor ARC-HBR criteria. CKD was defined as eGFR < 60mL/min/1.73m2. These HBR patients were divided into 3 groups: eGFR < 30mL/min/1.73m2 defined as severe CKD (N = 221), eGFR 30- < 60mL/min/1.73m2 defined as moderate CKD (N = 970), eGFR ≥ 60mL/min/1.73m2 defined as no CKD (N = 1,109). The primary endpoint was the composite of cardiac death, myocardial infarction, or stent thrombosis, and the safety endpoint was major bleeding up to 4-year follow-up. HBR patients with CKD were more often female and had higher rates of comorbidities compared to those without CKD. Reduced renal function was associated with higher rates of the primary endpoint (severe CKD vs. moderate CKD vs. no CKD: 30.2% vs. 12.5% vs. 9.1%, P < 0.01) as well as major bleeding (10.3% vs. 8.9% vs. 6.4%, P = 0.03). After adjustment, severe CKD and moderate CKD in HBR patients remained independent predictors for the primary endpoint (HR [95%CI] 2.84 [1.94-4.16], P < 0.01, 1.48 [1.10-2.00], P < 0.01) compared to those with no CKD. However, decreased renal function was no longer significantly associated with major bleeding after adjustment. In conclusions, in HBR patients undergoing PCI, CKD has an important impact on major ischemic events after PCI.

ObjectiveIn the Apixaban for Prevention of Acute Ischemic Events (APPRAISE-2) trial, the use of apixaban, when compared with placebo, in high-risk patients with a recent acute coronary syndrome (ACS) resulted...

Abbreviated or Standard Antiplatelet Therapy After PCI in Diabetic Patients at High Bleeding Risk

Background Bleeding events incidence has gained a crucial role in acute coronary patients (ACS) due to its independent effect prognostic value. Methods We assessed the trend of in-hospital and first-year-after-discharge major bleeding events (MB) in all ACS admitted in a single center between January 2009 and Agoust 2019. MB was defined as those fitting definitions 3 or 5 of the BARC consortium. Patients were categorized as high-bleeding risk (HBR) if according to the 2019 Academic Research Consortium HBR consensus if they met at least one major or two minor criteria. Inclusion period was divided in 3 groups: 2009–2012 (n=884; 27.4%), 2013–2015 (n=1,047; 32.5%); 2016–2019 (n=1,294; 40.1%). Post-discharge MB was assessed by competing events regression models, taking all-cause mortality as a competing event, and results are presented as sub-hazard ratio (sHR). Results We included 3225 patients, mean age was 68.4 (29.7), 25.7% females, 1,108 32.1% had diabetes and 44.0% STEMI. Radial access was perfume in 92% of the angiographies in the 3 time-periods. A significant decrease in dual antiplatelet treatment (DAPT) before angiography was noted (69.0%; 56.3%; 53.6%; p=0.001) with a decreasing pattern in clopidogrel and increase in ticagrelor and prasugrel. A total of 1,591 (46.2%) were categorized as HBR patients. A non-significant trend to higher incidence of in-hospital MB was noted through the 3 time periods: 1.39%; 1.43%; 2.55% (p=0.056) and it was mainly driven by the significant increase only in HBR patients: 2.21%; 3.55%; 6.26% (p=0.003). Multivariate analysis identified age (OR: 1.06 95% CI 1.03–1.08, p&amp;lt;0.001) and the time period 2016–2019 (OR: 1.96 95% CI 1.01–3.84; p=0.031) as main variables associated to higher in-hospital MB. In contrast, postdischarge MB did not change overtime (p=0.155) and trends were the same in HBR and non-HBR patients (figure). The competing risk regression analysis, adjusted by age, gender, previous cardiovascular disease, revascularization and medical treatments, identified that the leading factors for postdischarge MB were diabetes (sHR: 1.37; 95% CI 1.01–2.92), time-period 2016–2019 (sHR: 1.52; 95% CI 1.01–2.30), HBR patient (sHR: 1.91; 95% CI 1.28- 2.87) and and previous heart failure (sHR: 2.26; 95% CI 1.264.40) Conclusions This continuous 10-year registry highlights the increasing trend of in-hospital mainly driven by the incidence in HBR patients. In contrast, postdischarge MB increased in all patients. Funding Acknowledgement Type of funding sources: None. Post-discharge MB incidence

In-hospital outcomes of Ticagrelor versus Clopidogrel in high bleeding risk patients with acute coronary syndrome: Findings from the CCC-ACS project

The polymer-free biolimus coated stent (BioFreedom) was shown to be superior to bare metal stents in the LEADERS FREE randomized trial in high bleeding risk (HBR) patients treated with 1-month dual antiplatelet therapy (DAPT). However, there is limited outcome data with this device in an all-comers' population. We conducted a prospective single-arm study of patients undergoing percutaneous coronary intervention with the polymer-free biolimus coated stent in 25 centers in France with wide inclusion criteria including multivessel disease, complex lesions, and acute coronary syndromes. The primary endpoint was the incidence of target lesion failure (TLF), a composite of cardiac death or target-vessel myocardial infarction (MI) or clinically indicated target lesion revascularization (ci-TLR) at 1-year. The patient population was classified according to the presence (or not) of HBR criteria according to the recent ARC-HBR definition. Between April 2019 and April 2020, 1497 patients were enrolled. TLF occurred in 101 (6.9%) patients, including cardiac death in 35 (2.4%), target vessel MI in 20 (1.4%) and ci-TLR in 65 (4.5%) of them. There were 491 HBR patients (32.8%) and 1006 non-HBR patients. The median duration of DAPT was 74 days in the HBR group versus 348 days in the non-HBR group (p < 0.0001). TLF occurred in 44 (9.2%) of the HBR group and in 57 (5.8%) of the non-HBR group (relative risk 1.62 [95% confidence interval: 1.10-2.41], p = 0015). Compared to the non-HBR group, HBR patients had higher rates of cardiac death (4.4% vs. 1.4%, p = 0.0005) and target vessel MI (2.9% vs. 0.6%, p = 0.0003), but similar rates of ci-TLR. BARC 3-5 bleeding occurred in 6.2% of the HBR group versus 1.4% of the non-HBR group (p < 0.0001). In this multicenter all-comers study, HBR patients treated with a polymer-free biolimus coated stent had, compared to non-HBR patients, an increased risk of cardiac death and MI, and despite a shorter duration of DAPT, continued to have higher rates of BARC 3-5 bleeding.

Whether the underlying risk of bleeding influences the associations between patterns of dual antiplatelet therapy (DAPT) cessation and adverse events after percutaneous coronary intervention is unknown. Patients enrolled in the prospective, international, multicenter PARIS registry (Patterns of Non-Adherence to Anti-Platelet Regimens in Stented Patients) were categorized according to their risk of bleeding using the PARIS bleeding risk score. We evaluated the incidence, patterns, and association between modes of DAPT cessation and outcomes across bleeding risk groups. Modes of DAPT cessations were defined as physician-guided DAPT discontinuation, brief interruption (<14 days) or disruption for bleeding, or noncompliance. The primary end point of interest was major adverse cardiac events, defined as the composite of cardiac death, myocardial infarction, or definite-probable stent thrombosis. From a total of 5018 patients, 513 (10.2%) were classified as high, 2058 (41.0%) as intermediate, and 2447 (48.8%) as low risk for bleeding. High bleeding risk (HBR) patients were older and had greater prevalence of comorbidities. Compared with non-HBR, HBR patients had higher rates of both ischemic and bleeding events. The cumulative incidence of DAPT cessation was higher in HBR patients, mostly driven by physician-guided discontinuation and disruption. Of note, DAPT disruption occurred in 17.7%, 10.4%, and 7.8% at 1 year and 22.0%, 15.1%, and 12.0% at 2 years (P<0.0001) in high, intermediate, and low bleeding risk groups, respectively. Physician-guided DAPT discontinuation was not associated with increased risk of major adverse cardiac events in both HBR and non-HBR patients, while DAPT disruption was associated with an increased risk of major adverse cardiac events across all bleeding risk groups. There was no interaction between bleeding risk status and clinical outcomes for any cessation mode. Patients at HBR remain at higher risk of adverse events. Disruption of DAPT is associated with an increased risk of major adverse cardiac events irrespective of the underlying bleeding risk. Physician-guided discontinuation of DAPT appears to be safe, irrespective of HBR.

Background Patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) remain at increased risk of recurrent ischemic events. An abbreviated dual antiplatelet therapy (DAPT) duration as short as 1 month has been suggested for those at high bleeding risk (HBR). Whether the benefits of 1-month DAPT are preserved in HBR patients presenting with non-ST-elevation ACS (NSTE-ACS) is subject of debate. Purpose To assess the impact of NSTE-ACS presentation on the ischemic and bleeding outcomes of HBR patients undergoing PCI with a cobalt-chromium everolimus-eluting stent followed by a 1-month versus 3-month DAPT. Methods The XIENCE Short DAPT Program encompasses three prospective, international, single-arm studies evaluating the safety and efficacy of a 1-month (XIENCE 28 USA and Global) or 3-month (XIENCE 90) DAPT duration. The program enrolled HBR patients who had undergone successful XIENCE stent implantation for acute or chronic coronary syndrome (excluding ST-elevation ACS). Event-free subjects discontinued DAPT at 1 or 3 months post-PCI. The primary endpoint was the composite of all-cause death or myocardial infarction (MI), while the key secondary endpoint was Bleeding Academic Research Consortium (BARC) type 2–5 bleeding between 1 and 12 months post-PCI. Ischemic and bleeding events associated with 1-month versus 3-month DAPT were assessed according to clinical presentation using propensity-score (PS) adjustment. Results Out of 3,364 HBR patients (n=1,392 on 1-month DAPT and n=1,972 on 3-month DAPT), 1164 (34.6%) underwent PCI for NSTE-ACS. At 12 months, the risk of death or MI was similar between 1- and 3-month DAPT in patients with (adjHR 1.12, 95% CI 0.73–1.70) and without NSTE-ACS (adjHR 0.92, 95% CI 0.65–1.29; p-interaction = 0.33). Landmark analysis between 1 and 3 months post-PCI showed significant treatment effect modification according to clinical presentation (p-interaction = 0.03) with greater benefit of 1-month DAPT in stable patients. BARC 2–5 bleeding was consistently reduced in both NSTE-ACS (adjHR 0.58, 95% CI 0.38–0.90) and stable patients (adjHR 0.86, 95% CI 0.63–1.18; p-interaction = 0.15). Conclusions Among HBR patients undergoing PCI with an everolimus-eluting stent, 1-month compared with 3-month DAPT was associated with similar 1-year risk of ischemic events and reduced bleeding, irrespective of clinical presentation. Between 1 and 3 months post-PCI, however, stable patients seemed to derive greater net benefit from 1-month DAPT compared to those with NSTE-ACS. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Abbott