Bleeding Academic Research Consortium Research Articles

Abstract 4135723: Efficacy and Safety of Ticagrelor with Aspirin vs Ticagrelor Monotherapy in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Background: Dual antiplatelet therapy (DAPT) consisting of ticagrelor, a P2Y 12 inhibitor, and aspirin, is the recommended treatment of acute coronary syndrome patients undergoing percutaneous coronary intervention (PCI). However, recently ticagrelor monotherapy has been shown to preserve ischemic protection while reducing bleeding risk in ACS patients. We aimed to compare the clinical outcomes of DAPT and ticagrelor monotherapy in ACS patients undergoing PCI. Methods: MEDLINE, Scopus, and EMBASE were queried up to May 2024 for randomized controlled trials (RCTs) comparing ticagrelor monotherapy after 1 to 3 months of DAPT versus continued DAPT for 12 months in ACS patients. The primary outcomes were all-cause death, net adverse clinical events (NACE) and Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding. Key secondary endpoints included BARC 3 or 5 bleeding, myocardial infarction (MI), hemorrhagic and ischemic stroke, and target vessel revascularization (TVR). A random-effects meta-analysis was performed to derive risk ratios (RR) and corresponding 95% confidence intervals (CI). Results: Six RCTs including 28,526 patients, with a mean age of 63.5 years, were included. DAPT was associated with a significantly higher risk of all-cause death (RR: 1.32, 95% CI: 1.05-1.64, P=0.02), NACE (RR: 1.20, 95% CI: 1.01-1.42, P=0.04), and BARC 2, 3, or 5 bleeding (RR: 1.96, 95% CI: 1.71-2.26, P<0.00001) compared to monotherapy. DAPT significantly increased the risk of BARC 3 or 5 bleeding (RR: 2.06, 95% CI: 1.69-2.51, P<0.00001) however, no association was seen in myocardial infarction (RR: 1.01, 95% CI: 0.84-1.20, P=0.94). Conversely, DAPT resulted in a non-significant reduction in ischemic (RR: 0.94, 95% CI: 0.63-1.41, P=0.77) and hemorrhagic stroke (RR: 0.83, 95% CI: 0.36-1.95, P=0.67). Additionally, no significant association could be ascertained in TVR (RR: 1.18, 95% CI: 0.94-1.48, P=0.15). Conclusion: Our analysis highlights the elevated risks of all-cause death, NACE, and major bleeding with DAPT compared to monotherapy in ACS patients post-PCI, favoring the latter for safety. Future investigations should refine antiplatelet therapy durations and identify specific patient subsets for optimal DAPT utilization.

Temporal modulation (early escalation and late de-escalation) of antiplatelet therapy in patients undergoing complex high-risk PCI: rationale and design of the TAILORED-CHIP trial.

Despite the use of conventional dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI), the risk of adverse events remains high among patients with increased thrombotic risk. Until recently, the optimal antiplatelet strategy to balance the ischaemic and bleeding risks in patients who are undergoing complex high-risk PCI has been unclear. The TAILored Versus COnventional AntithRombotic StratEgy IntenDed for Complex HIgh-Risk PCI (TAILORED-CHIP) trial is an investigator-initiated, multicentre, prospective randomised trial to evaluate the efficacy and safety of a time-dependent tailored antiplatelet therapy with an early (<6 months post-PCI) escalation (low-dose ticagrelor at 60 mg twice daily plus aspirin) and a late (>6 months post-PCI) de-escalation (clopidogrel monotherapy) in patients undergoing complex high-risk PCI as compared with standard DAPT (clopidogrel plus aspirin for 12 months). Eligible patients had to have at least one high-risk anatomical or procedural feature or clinical characteristic associated with an increased risk of ischaemic or thrombotic events. The primary endpoint was the net clinical outcome, a composite of death from any cause, myocardial infarction, stroke, stent thrombosis, urgent revascularisation, or clinically relevant bleeding (Bleeding Academic Research Consortium type 2, 3, or 5) at 12 months after randomisation. (ClinicalTrials.gov: NCT03465644).

Culprit vessel revascularization prior to complete angiography as a strategy to minimize delays in primary percutaneous coronary intervention for patients with ST-elevation myocardial infarction: a systematic review and meta-analysis.

The rapid restoration of blood flow in patients with acute myocardial infarction with ST elevation through percutaneous coronary intervention (PCI) is crucial for the survival of this population. Attempts to decrease the time from diagnosis of ST-segment elevation myocardial infarction (STEMI) to arrival at the catheterization laboratory have been extensively investigated. However, strategies during the procedure aiming to reduce the time to reperfusion are lacking. We conducted a meta-analysis to evaluate culprit vessel revascularization prior to complete angiography as a strategy to minimize delays in primary PCI for patients with STEMI. We searched PubMed, Embase, and Cochrane Central. Outcomes: vascular access-to-balloon, door-to-balloon, and first medical contact-to-balloon times; death, reinfarction in 30 days, Bleeding Academic Research Consortium ≥3 type, coronary artery bypass grafting referral, and left ventricular ejection fraction %. Statistical analysis was performed using the R program (version 4.3.2). Heterogeneity was assessed with I2 statistics. We included 2050 patients from six studies, of which two were randomized controlled trials and four were observational studies. Culprit vessel revascularization prior to complete angiography was associated with a statistically significant decrease of times: vascular access-to-balloon time (mean difference -6.79 min; 95% CI: -8.00 to -5.58; P < 0.01; I2 = 82%) and door-to-balloon time (mean difference -9.02 min; 95% CI: -12.83 to -5.22; P < 0.01; I2 = 93%). In this meta-analysis, performing PCI on the culprit lesion prior to complete coronary angiography led to significantly shorter reperfusion times, with no discernible differences in complication rates.

Risk score guided dual antiplatelet therapy duration in patients with acute coronary syndrome: insights from the FORCE-ACS registry

Abstract Background The use of risk scores to guide the duration of dual antiplatelet therapy(DAPT) in patients with acute coronary syndrome(ACS) is recommended in current guidelines, however clinical data on the impact of its prospective use is lacking. Purpose To compare risk-score guided DAPT duration to standard of care in ACS patients. Methods Since 2015, patients with ACS are enrolled in the prospective FORCE-ACS registry. In 2018, we implemented a risk score-guided approach for DAPT duration. In this analysis, we compared patients in which DAPT duration was guided by bleeding and ischemic risk assessment using PRECISE-DAPT-scores and DAPT-scores to a standard treatment group in a 1:4 ratio. In risk score-guided patients, high bleeding risk patients(HBR) were advised short DAPT(≤6 months); patients without HBR or high ischemic risk(HIR) were advised 12 months DAPT; and patients without HBR but with HIR were advised prolonged DAPT(≥30 months). In the standard treatment group DAPT duration was left at the discretion of the treating physician. Exclusion criteria included no DAPT or oral anticoagulation at discharge or implanted bio-vascular stents. Primary outcome was a composite of all-cause mortality, myocardial infarction(MI), stent thrombosis(ST), stroke and Bleeding Academic Research Consortium(BARC) 3 or 5 bleeding; a secondary composite ischemic outcome consisted of cardiovascular mortality, MI, ST and ischemic stroke. Kaplan-Meier plots with log-rank testing and Cox proportional hazard regression after adjustment of potential confounders were performed for the primary outcome. Sensitivity analyses were performed for patients included after implementation of the risk score-guided approach and for censoring events within the first six months. Results Between 2015 and 2020 8,009 patients were enrolled in the FORCE-ACS registry, of which 5,518 patients were included for analysis. The risk-score guided group(n=1,200) more often presented with ST-elevation MI, percutaneous coronary intervention or optimal medical therapy, while standard treatment patients(n=4,318) were older, more often had prior MI, prior revascularization, received coronary artery bypass grafting or conservative management. In the risk-score guided group, 15.7% had HBR, 46.4% were without HBR or HIR, and 37.9% showed HIR without HBR. The primary outcome was 6.3%(n=75) in risk score-guided patients versus 14.8%(n=637) in the standard treatment group (adjusted hazard ratio(HR) 0.47 [95%CI 0.36–0.61], p&amp;lt;0.001). These results remained consistent after sensitivity analyses (fig 1B). Both the composite ischemic outcome(HR 0.54 [95%CI 0.41–0.72] p&amp;lt;0.001) and BARC 3 or 5 bleeding (HR 0.23 [95%CI 0.08-0.63], p=0.004) were significantly lower in risk score-guided patients compared to the standard treatment group. Conclusion In this prospective analysis, risk-score guided DAPT duration showed a significant reduction of both ischemic and bleeding events compared to standard treatment.

The safety and efficacy of indobufen or aspirin combined with clopidogrel in patients with acute myocardial infarction after percutaneous coronary intervention

Abstract Background Currently, the standard treatment for patients who have undergone percutaneous coronary intervention (PCI) following acute myocardial infarction (MI) involves dual antiplatelet therapy (DAPT) with a combination of asprin and clopidogrel. However, the potential benefits of aspirin were limited by an increased risk of bleeding. The safety and efficacy of indobufen, an alternative antiplatelet agents to aspirin, in patients with AMI after PCI are yet to be thoroughly investigated. Methods This retrospective study was conducted at a single center and utilized propensity score matching. The enrollment spanned from January 2019 to June 2022, incorporating patients who experienced AMI following PCI. The participants were categorized into two groups based on their medication: the aspirin DAPT group and the indobufen DAPT group. The primary endpoint focused on net adverse clinical event (NACE) at one year, defined as a composite outcome, including cardiac death, recurrence of MI, definite or probable stent thrombosis (ST), target lesion revascularization (TLR), ischemic stroke and Bleeding Academic Research Consortium (BARC) criteria type 2, 3, or 5. Results A total of 1451 patients were enrolled in this study, with 258 assigned to the indobufen DAPT group and 1193 to the aspirin DAPT group. Following 1:1 propensity score matching, 224 patients were retained in each group and postmatching absolute standardized differences were consistantly below 10% for all covariates (Figure 1). The primary endpoint occurred in 58 (25.9%) individuals in indobufen DAPT group and 52 (23.2%) in the aspirin DAPT group (HR 1.128, 95% CI 0.776-1.639, p = 0.527, Figure 2). Specifically, no significant differences were observed in either the efficacy endpoint (MACCE, 20.1% vs. 14.7%, HR 1.392, 95% CI 0.893-2.170, p = 0.146) or the safety endpoint (BARC 2,3 or 5, 8.04% vs. 10.30%, HR 0.779, p=0.427). Conclusions The results of our study reveal no noteworthy distinctions in primary and secondary endpoints between the two groups. This finding indicates that the efficacy and safety of indobufen may be comparable to aspirin in Chinese patients with AMI after PCI, supporting its consideration as a potential substitute for aspirin in patients with AMI after PCI.

Rivaroxaban or warfarin in atrial fibrillation and coronary stent implantation in real-world patients involving chronic kidney disease (REWRAPS): 5-year follow-up study

Abstract Background Recent guidelines recommended either non vitamin K antagonist oral anticoagulants (NOAC) or vitamin K oral anticoagulant (VKA) one year after coronary stenting in patients with atrial-fibrillation (AF). However, whether NOAC is still superior to VKA at 5-years in patients involving chronic kidney disease (CKD) with AF and coronary stenting &amp;gt;1-year remains unclear. Methods In a multicenter, prospective, non-randomized registry, 493 patients were treated with either rivaroxaban or warfarin, while the majority (66.3%) of them had CKD. The primary efficacy endpoint was major adverse cardiac and cerebral events (MACCE). The primary safety endpoint was major bleeding (Bleeding Academic Research Consortium [BARC] 3 and 5). Net adverse clinical events (NACE) were defined as the composite of all-cause mortality and major bleeding. Both crude and propensity score matched (PSM) analyses were performed. P &amp;lt;0.05 was considered as statistically significant. Results At a median follow-up of 4.8 years MACCE rates did not differ between rivaroxaban and warfarin in 486 patients with crude-analysis (23.0% versus 29.0%, hazard-ratio [HR], 0.79; 95% confidence interval [CI], 0.55 to 1.11; P=0.17), while in 316 patients with PSM-analysis rivaroxaban met non-inferiority criteria to warfarin (HR, 0.86; 95% CI, 0.56 to 1.33; p=0.020 for non-inferiority). Rivaroxaban was associated with lower major bleeding risk compared with warfarin (6.5% versus 12.6%; HR, 0.50; 95% CI, 0.27 to 0.91; P=0.025) at crude analyses, which was no longer significant at PSM analyses (5.7% versus 10.8%; HR, 0.53; 95% CI, 0.24 to 1.19; P=0.12). However, NACE rates were significantly lower in rivaroxaban compared to warfarin at both crude (19.0% versus 35.7%; HR, 0.50; 95% CI, 0.35 to 0.72; P=0.0002) and PSM-analyses (19.6% versus 31.0%; HR, 0.63; 95% CI, 0.40 to 0.98; P=0.043), respectively. Conclusions Rivaroxaban did not differ from warfarin for efficacy endpoints of MACCE but was associated with lower NACE rates (i.e. all-cause mortality and major bleeding) in AF and coronary stent in real-world patients having CKD at 5-year follow-up (NCT02024230).

Ticagrelor vs. clopidogrel in ST elevation myocardial infarction patients with hemoglobin &amp;gt; 160

Abstract Background While some studies have provided therapeutic guidance for antiplatelet therapy in acute coronary syndrome (ACS) patients with anemia, research regarding ACS patients with elevated hemoglobin remains scarce. Purpose This study aims to evaluate the prognostic impact of different dual antiplatelet therapy (DAPT) regimens in ST-segment elevation infarction (STEMI) patients with hemoglobin &amp;gt; 160 g/L. Methods The data for this study were derived from the Health and Medical Big Data Superplatform, comprising a retrospective cohort of patients admitted to and discharged from 72 secondary and tertiary hospitals from 2010 to 2023. A total of 3372 patients were included in the study. Patients were divided into either the ticagrelor group or the clopidogrel group based on their priscribed antiplatelet regimens. The primary endpoint was defined as major adverse cardiovascular and cerebrovascular events (MACCE), comprising of cardiac death, myocardial infarction, and ischemic stroke within one month. Secondary endpoints included all-cause death at one-year, net adverse clinical events (NACE) defined as cardiac death, recurrent MI, Bleeding Academic Research Consortium (BARC) level 3 or greater, and revascularization, and cardiac death at one year. Propensity score matching (PSM) was utilized to balance clinical characteristics between the two groups. Multivariable Cox regression analysis was conducted post PSM to evaluate the impact of different antiplatelet regimens. Result The study population comprised 3372 patients, with 2200 receiving clopidogrel and 1172 with ticagrelor. The median age in the clopidogrel group was 54.83 years, while in the ticagrelor group, it was 53.61 years (P = 0.005). The clopidogrel group had a higher proportion of females compared to the ticagrelor group (3.9% vs. 2.0%, p=0.003). After PSM, 1086 well-matched pairs were identified. The ticagrelor group demonstrated a significantly lower rate of one-year all-cause mortality (1.38% VS 2.85%, LogRank p = 0.018), MACCE events (6.53% VS 9.48%, LogRank p = 0.015), and cardiac death (1.29% VS 2.76%, LogRank p = 0.015), compared to the clopidogrel group. However, there was no significant difference in the incidence of NACE events between the two groups (8.38% VS 7.76%, p = 0.300). Multivariate Cox regression analysis showed that ticagrelor treatment was associated with a reduced risk of all-cause mortality ( aHR 0.408, 95%CI: 0.214-0.775, p = 0.006), MACCE events (aHR 0.640, 95%CI: 0.473-0.869, p = 0.042), cardiac death (aHR 0.384, 95%CI: 0.198-0.743, p = 0.004). Conclusions Among STEMI patients with hemoglobin &amp;gt; 160 g/L, treatment with ticagrelor was associated with significantly lower rates of all-cause mortality, MACCE, and cardiac death compared to the treatment with clopidogrel.

Association of ticagrelor vs clopidogrel with net adverse clinical events in NSTEMI patients with mild thrombocytopenia

Abstract Backgrounds: Guidelines currently recommend aspirin plus ticagrelor as the preferred dual antiplatelet therapy (ADPT) for non-ST-elevation myocardial infarction (NSTEMI). However, there are no established recommendations for managing NSTEMI patients with mild thrombocytopenia, defined as a platelet count of 100~150×109/L. Purpose This study aims to investigate the association between ticagrelor and clopidogrel with ischemic and hemorrhagic events in NSTEMI patients with a platelet count of 100~150×109/L. Methods A retrospective cohort study was conducted using data from the Health and Medical Big Data Super Platform from January 2010 to June 2023. The study included NSTEMI patients with a platelet count of 100~150×109/L who received DAPT consisting of aspirin and a P2Y12 receptor antagonist (eithor clopidogrel or ticagrelor). Patients were followed up for at least one year. The inverse probability of treatment weighting (IPTW) approach based on propensity score was used to balance the observed confounders between treatments. The primary endpoint was net adverse events (NACE) at 1 year, composed of ischemic events (recurrent myocardial infarction or ischemic stroke), Bleeding Academic Research Consortium (BARC) classification ≥ 3, and cardiac death. Secondary outcomes included cardiac death, recurrent myocardial infarction and, ischemic stroke. Results The study cohort comprised 2969 participants, with a median age of 72 years and 29.2.0% female. After adjustment using inverse probability of treatment weighting, ticagrelor and clopidogrel showed similar rates of NACE (aHR, 0.84; 95%Cl, 0.58-1.21). Cardiac death (aHR, 0.99; 95%Cl, 0.54-1.83) and ischemic stroke (aHR, 0.94; 95%Cl, 0.49-1.81) did not significantly differ between the two groups. However, ticagrelor was associated with a lower rate of recurrent myocardial infarction (aHR, 0.44; 95%Cl, 0.21-0.93). Conclusion In routine clinical practice, among NSTEMI patients with a platelet count of 100~150×109/L, ticagrelor, did not showed a significant difference in the risk of NACE at 1 year compared with clopidogrel. However, ticagrelor was associated with a lower rate of recurrent myocardial infarction. Further research is warranted to confirm the this conclusion.

Association of ticagrelor vs clopidogrel with net adverse clinical events in patients with mild thrombocytopenia undergoing PCI

Abstract Backgrounds Current guidelines recommend aspirin plus ticagrelor as the preferred dual antiplatelet therapy (DAPT) for managing ST-elevation myocardial infarction (STEMI). However, there is a lack of consensus or guidelines to direct clinicians on managing patients with mild thrombocytopenia, defined as a platelet count of 100~150×109/L, undergoing percutaneous coronary intervention (PCI). Purpose This study aims to investigate the association between ticagrelor and clopidogrel with ischemic and hemorrhagic events for patients with mild thrombocytopenia undergoing PCI. Methods A retrospective cohort study of patients with mild thrombocytopenia undergoing PCI who received DAPT consisting of aspirin and a P2Y12 receptor antagonist (includinig clopidogrel or ticagrelor) was conducted using Health and Medical Big Data Super Platform from January 2010 to June 2023. All patients meeting the criteria were included in the analysis, with a follow-up of at least one year. Propensity Score Matching (PSM) was performed to equalize the effects of following characteristics: age, sex, hypertension, diabetes, dyslipidemia, stroke, atrial fibrillation, Killip class, percutaneous coronary intervention (PCI), beta-blockers, statins, calcium channel blockers (CCB), angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (ACEI or ARB), angiotensin receptor-neprilysin inhibitor (ARNI), diuretic, organic nitrates, and oral anticoagulation. The primary endpoint was net adverse clinical events (NACE) at 1 year, composed of ischemic events (recurrent myocardial infarction or ischemic stroke), Bleeding Academic Research Consortium (BARC) classification ≥ 3, and cardiac death. Secondary outcomes included the components of NACE. Results A total of 3647 patients met the inclusion criteria, with 2684 receiving aspirin plus clopidogrel and 963 receiving aspirin plus ticagrelor, matched by a 1:3 ratio using the PSM method. Demographic characteristics were well balanced between the clopidogrel and ticagrelor groups. The 1-year risk of NACE did not significantly differ between ticagrelor and clopidogrel (11.1% vs. 8.4%, p=0.370). Similarly, there was no significant difference in the risk of cardiac death (7.3% vs. 4.2%, p=0.720), recurrent myocardial infarction (9.3% vs. 5.8%, p=0.550), ischemic stroke (8.8% vs. 6.7%, p=0.055), or BARC type ≥ 3 bleeding (7.9% vs. 4.5%, p=0.990). Conclusion In routine clinical practice, among patients with a platelet count of 100~150×109/L undergoing PCI, ticagrelor compared with clopidogrel was not associated with a significant difference in the risk of NACE at 1 year. Further research is warranted to assess whether ticagrelor is more effective than clopidogrel in this setting, considering potential unmeasured confounders.

The impact of body mass on cardiovascular outcomes in patients with acute coronary syndrome

Abstract Background Patients with acute coronary syndrome (ACS) and extreme body weights exhibit varying risks of bleeding and thrombotic outcomes. Furthermore, extreme body weights can influence the pharmacodynamic response to potent P2Y12 inhibitors (ticagrelor/prasugrel) and clopidogrel. Purpose This study aims to assess the impact of extreme body weights on cardiovascular outcomes, as well as the comparative efficacy and safety of potent P2Y12 inhibitors versus clopidogrel. Methods Data was extracted from the FORCE-ACS registry, a prospective, multicentre, registry, enrolling patients with ACS. Patients were stratified (in kg/m2) into the categories: underweight (body mass index [BMI] ≤20.0), normal weight (20.1–24.9), overweight (25.0–29.9), class 1 (30.0–34.9) and class 2 obesity (≥35.0). The primary thrombotic endpoint was major adverse cardiac events (MACE), a composite of cardiovascular death, myocardial infarction (MI), or stroke. The primary bleeding endpoint was defined as Bleeding Academic Research Consortium (BARC) 2, 3 or 5 bleeding. Cox proportional hazard models and Kaplan-Meier survival curves were used to estimate the risk of clinical events across the BMI categories. Restricted cubic splines were made to assess the continuous association of BMI with the risk of the primary endpoints, stratified for P2Y12-inhibitor therapy (potent vs. clopidogrel) and gender. Results The total included population consisted of 5,864 patients with ACS (mean age 65.2 years, 72.4% men), and were stratified into underweight (N=112 [2%]), normal weight (N=1,627 [28%]), overweight (N=2,697 [46%]), class 1 obesity (N=1,081 [18%]) and class 2 obesity (N=347 [6%]). Compared with normal weight (10.8%), the rate of primary bleeding outcome was higher in underweight (15.2%) patients, but lower in the overweight (8.9%), class 1 obesity (7.9%) and class 2 obesity (6.3%) categories. MACE occurred in 9.8% for the underweight group, 7.9% for normal weight, 7.0% for overweight, 8.0% for class, and 6.1% for class 2 obesity. After adjusting for confounding factors such as age, gender, cardiovascular risk factors, access site, and medical therapy, each unit increase in BMI was associated with a decreased bleeding risk (hazard ratio [HR] 0.97, 95% CI 0.95-0.99, p = 0.02), with no significant association found for MACE. Similar findings are demonstrated in the Kaplan Meier analysis (Figure 1A-1B). Subgroup analysis regarding bleeding risk and BMI did not show a significant interaction for potent P2Y12-inhibitor therapy versus clopidogrel and gender (P-value for interaction: 0.04 and 0.32, respectively)(Figure 2A-2D). Conclusions Our findings indicate a stronger correlation between BMI and bleeding risk compared to thrombotic risk, showing an increased risk for bleeding in patients with a low BMI. These results underscore the importance of careful monitoring and tailored interventions to mitigate bleeding risk in underweight patients.

Antiplatelet can improve the short-term prognosis of type 2 myocardial infarction caused by acute respiratory failure

Abstract Background Type 2 myocardial infarction (T2MI) is characterized by myocardial infarction resulting from an imbalance between myocardial oxygen supply and demand, without the rupture of acute atherosclerotic plaque. Antiplatelet therapy is the cornerstone of treatment for Type 1 myocardial infarction, however, its efficacy in T2MI remains unclear. Purpose This study aimed to explore the impacts of antiplatelets on prognosis in patients with T2MI caused by acute respiratory failure. Methods The data for this study were derived from the Health and Medical Big Data Superplatform, comprising a retrospective cohort of patients admitted to and discharged from 72 secondary and tertiary hospitals from 2010 to 2023. A total of 4708 patients with T2MI due to acute respiratory failure were included. Participants were divided into two groups: those receiving antiplatelet therapy and those not. T2MI caused by acute respiratory failure was defined as NSTEMI patients caused by respiratory failure without percutaneous coronary intervention (PCI). Propensity score matching (PSM) was used to balance covariates between the groups, followed by building a multivariable Cox regression model to further adjust for potential confounders. Covariates adjusted in multivariable Cox regression included antiplatelet, anticoagulant, and lipid-lowering drug use during hospitalization, age, sex, KILLIP classification, history of diabetes, hypertension, percutaneous coronary intervention, stroke, renal insufficiency, cerebral hemorrhage, and atrial fibrillation. One-to-one matching was performed based on propensity scores using the nearest available pair matching method with a caliper width of 0.01. The primary endpoint was Net Adverse Clinical Events (NACE) within 1 month, including myocardial infarction, cardiac death, stroke and Bleeding Academic Research Consortium (BARC) criteria type 3 or 5. Results Following 1:1 propensity score matching, a total of 1418 participants were enrolled in the final study sample, with 709 patients retained in each group. Patients using antiplatelet were more likely to use ACEI/ARB, CCB, and β-blockers during hospitalization, all p&amp;lt;0.05.Compared to non-antiplatelet therapy group, the use of antiplatelet was associated with a 0.69 times risk of 1-month NACE (aHR, 0.69; p&amp;lt;0.001), a 0.69 times risk of 1-month Major Adverse Cardiovascular and Cerebrovascular Events (MACCE) (aHR, 0.69; p&amp;lt;0.001), a 0.70 times risk of 1-month cardiac death (aHR, 0.70; p&amp;lt;0.001), and a 0.70 times risk of 1-month all-cause mortality (aHR, 0.70; p&amp;lt;0.001); with no statistical significance for other clinical outcomes (p &amp;gt; 0.05) (Figure 1). Conclusions The present study suggested that patients receiving antiplatelet therapy had a lower incidence of one-month NACE, primarily due to a reduction in major cardiac death and MACCE at 1 month.

Association of ticagrelor vs clopidogrel with net adverse clinical events in STEMI patients with mild thrombocytopenia

Abstract Backgrounds Current guidelines advocate for aspirin plus ticagrelor as the preferred dual antiplatelet therapy (DAPT) for ST-elevation myocardial infarction (STEMI). However, there is a lack of consensus or guidelines to direct clinicians on managing STEMI patients with mild thrombocytopenia, defined as a platelet count of 100~150×109/L. Purpose This study aims to investigate the association between ticagrelor and clopidogrel with ischemic and hemorrhagic events in STEMI patients with a platelet count of 100~150×109/L. Methods A retrospective cohort study was conducted using Health and Medical Big Data Super Platform from January 2010 to June 2023.The study included STEMI-patients with a platelet count of 100~150×109/L who received DAPT consisting of aspirin and a P2Y12 receptor antagonist (either clopidogrel or ticagrelor) All STEMI patients with a platelet count of 100~150×109/L were included in the analysis with a follow-up of at least one year. The inverse probability of treatment weighting (IPTW) approach based on propensity score was utilized to balance observed confounders between treatments. The primary endpoint was net adverse events (NACE) at 1 year, including ischemic events (recurrent myocardial infarction or ischemic stroke), Bleeding Academic Research Consortium (BARC) classification ≥ 3, and cardiac death. Secondary outcomes were cardiac death, recurrent myocardial infarction, and ischaemic stroke. Results The study cohort consisted 2941 participants with median age of 69 years, and 21.0% were female. Following adjustment using the inverse probability of treatment weighting, ticagrelor and clopidogrel demonstrated similar NACE (aHR, 0.86; 95%CI, 0.60-1.23). Cardiac death (aHR, 0.69; 95%CI, 0.36-1.31), recurrent myocardial infarction (aHR, 0.94; 95%CI, 0.50-1.78), and ischaemic stroke (aHR, 0.62; 95%CI, 0.34-1.14) did not significantly differ between the two groups. Conclusion In routine clinical practice, among STEMI patients with a platelet count of 100~150×109/L ticagrelor compared with clopidogrel, was not associated with a significant difference in the risk of NACE at 1 year. Further research is warranted to assess whether ticagrelor is more effective than clopidogrel in this particular patient population.

Drug-coated balloon versus drug-eluting stent revascularization in the treatment of de novo acute myocardial infarction

Abstract Objective To assess the efficacy and safety of a drug-coated balloon (DCB) revascularization on percutaneous coronary intervention (PCI) in patients with de novo acute myocardial infarction (AMI). Background Data on DCB-only treatment in the context of AMI are limited. Methods A total of 96 patients with de novo AMI successfully treated with DCB alone were retrospectively enrolled. Visual residual stenosis ≤ 30% without flow-limiting dissection was considered a satisfactory pre-balloon angioplasty and followed by DCB treatment. We compared it with 96 propensity-matched patients treated with second-generation drug-eluting stent (DES) from the PTRG-DES registry (n = 13,160 patients). Major adverse cardiovascular events (MACE) comprised cardiac death, myocardial infarction, stroke, stent or target lesion thrombosis, target vessel revascularization, and major bleeding (Bleeding Academic Research Consortium bleeding type 3 or greater) at 1 year. Results Baseline clinical characteristics were comparable between the groups. The mean device diameter was larger in DES group (2.7 ± 0.3 mm vs. 3.1 ± 0.4 mm, P &amp;lt; 0.001). No abrupt vessel closure requiring treatment occurred after treatment with DCB. The MACE was comparable in both groups (6.2% in DCB group vs. 7.3% in DES group, P = 0.790) at 1-year follow-up. Conclusions In de novo AMI patients, DCB-only treatment approach had comparable clinical outcomes at 1-year follow-up. DCB-only treatment may be a safe and effective alternative to DES in carefully selected patients who had satisfactory pre-dilation results.

Thirty days clinical outcomes following stent implantation with aspirin-free prasugrel monotherapy in non-ST segment elevation myocardial infarction. Interim report from ASET-Japan pilot study

Abstract Background Dual antiplatelet therapy with a P2Y12 inhibitor, in addition to aspirin, is the standard therapy after percutaneous coronary intervention (PCI) for non-ST-segment elevation acute coronary syndrome (NSTE-ACS) to prevent ischemic cardiovascular events. The Acetyl-Salicylic Elimination Trial (ASET) pilot studies conducted in Japan in patients with NSTE-ACS investigated the safety and feasibility of a low-dose prasugrel monotherapy after PCI. Purpose To ensure the safety of the patients, enrolment in the study was implemented only after confirmation of a successful procedure. The abstract reports our interim analysis, aimed at evaluating preliminary safety and feasibility. Methods The ASET-Japan pilot study was designed to explore the feasibility and safety of a low dose of prasugrel monotherapy (3.75mg/day), without adjunctive aspirin, after optimal PCI using Everolimus eluting stent (EES) in Japanese patients with non-ST-segment elevation acute coronary syndromes. The primary endpoint in the ASET-Japan NSTE-ACS (Phase 2) is a 12-month clinical outcome. The study is currently in the follow-up phase. All the target lesions were treated with a platinum-chromium everolimus-eluting stent. The primary ischemic endpoint was the composite of cardiac death, spontaneous target vessel myocardial infarction, or definite stent thrombosis, and the primary bleeding endpoint was Bleeding Academic Research Consortium types 3 and 5 bleeding up to 12-month. If more than 3 events occurred, trial enrollment would have to be terminated by the data and safety monitoring board. Results One hundred one patients were enrolled after successful index PCI and completed a 30 days follow-up. The mean age was 69.1±12.3 years and 75.2% was male. The mean anatomical SYNTAX score was 7.9±4.7. Unstable angina (UAP) and NSTEMI were seen in 24.8% (25/101) and 75.2% (75/101) patients, respectively. According to the Braunwald classification, 8 percent of the patients were categorised as Class IA UAP, 48% as Class IB, 20% as Class IIB, 4% as Class IIIA and 20% as Class IIIB. In NSTEMI patients, the median (IQR) pre-procedural troponin value (cardiac Troponin T or I) was 2.79 (1.12 – 22.27) times the Upper Limit of Normal. According to the PRECISE DAPT score, 36.6% of patients were categorised as High Bleeding Risk (HBR) with scores above 25. At one month, the primary ischemic endpoints of cardiac death, target-vessel spontaneous MI or definite Stent thrombosis did not occur. Two patients (2.0%) had BARC type 3a bleeding. Conclusion Prasugrel monotherapy in the first 30 days following platinum-chromium everolimus-eluting stent deployment is a feasible and safe strategy in NSTE-ACS patients with simple anatomy and successful PCI.

Clinical implications of hepatorenal function in patients undergoing percutaneous coronary intervention: insights from the SAKURA PCI2 registry

Abstract Background Hepatorenal function is a prognostic predictor for heart failure, cardiac surgery, and transcatheter intervention for structural heart disease. However, the clinical implications of hepatorenal function assessed by the Model for End-stage Liver Disease eXcluding International normalized ratio (MELD-XI) score is still unclear in patients undergoing percutaneous coronary intervention (PCI). Purpose This study aimed to clarify the association between clinical prognosis and the MELD-XI score. Methods We analyzed 993 patients who underwent PCI from June 2020 to July 2022 in the SAKURA PCI2 registry, a prospective multicenter registry. Patients were stratified into high (&amp;gt;10) or low (≤10) MELD-XI scores. Primary outcome was defined as 2-year major adverse cardio or cerebrovascular event (MACCE), including all-cause death, ischemic stroke, and non-fatal myocardial infarction. Secondary outcome was defined as major bleeding according to the Bleeding Academic Research Consortium 3 or 5. Results Of study participating patients, 253 patients (25.5%) were stratified into a high MELD-XI score group and had a higher prevalence of the high bleeding risk than patients with a low MELD-XI score (92.5% vs. 53.7%, p&amp;lt;0.01). Patients with a high MELD-XI score were associated with MACCE (13.1% vs. 2.7%, p&amp;lt;0.01; adjusted HR 3.78, 95%CI 1.78-8.03, p&amp;lt;0.01) and major bleeding (4.0% vs. 1.3%, p&amp;lt;0.01: unadjusted HR 3.32, 95%CI 1.35-8.18, p=0.01). Moreover, these associations remained consistent in patients with chronic and acute coronary syndrome (MACCE, p for interaction=0.89; major bleeding; p for interaction=0.64). Conclusion A high MELD-XI score was associated with an increased risk of MACCE and major bleeding within two years. Therefore, the MELD-XI score could provide information for risk stratification in patients undergoing PCI.Outcomes

Derivation and Validation of the PRECISE-HBR Score to Predict Bleeding After Percutaneous Coronary Intervention.

Accurate bleeding risk stratification after percutaneous coronary intervention (PCI) is important for treatment individualization. However, there is still an unmet need for a more precise and standardized identification of high bleeding risk patients. We derived and validated a novel bleeding risk score by augmenting the PRECISE-DAPT score with the Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria. The derivation cohort comprised 29,188 patients undergoing PCI, of whom 1136 (3.9%) had a Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding at 1 year, from four contemporary real-world registries and the XIENCE V USA trial. The PRECISE-DAPT score was refitted with a Fine-Gray model in the derivation cohort and extended with the ARC-HBR criteria. The primary outcome was BARC 3 or 5 bleeding within 1 year. Independent predictors of BARC 3 or 5 bleeding were selected at multivariable analysis (p<0.01). The discrimination of the score was internally assessed with apparent validation and cross-validation. The score was externally validated in 4578 patients from the MASTER DAPT trial and 5970 patients from the STOPDAPT-2 total cohort. The PRECISE-HBR score (age, estimated glomerular filtration rate, hemoglobin, white-blood-cell count, previous bleeding, oral anticoagulation, and ARC-HBR criteria) showed an area under the curve (AUC) for 1-year BARC 3 or 5 bleeding of 0.73 (95% CI, 0.71-0.74) at apparent validation, 0.72 (95% CI, 0.70-0.73) at cross-validation, 0.74 (95% CI, 0.68-0.80) in the MASTER DAPT, and 0.73 (95% CI, 0.66-0.79) in the STOPDAPT-2, with superior discrimination than the PRECISE-DAPT (cross-validation: Δ AUC, 0.01; p=0.02; MASTER DAPT: Δ AUC, 0.05; p=0.004; STOPDAPT-2: Δ AUC, 0.02; p=0.20) and other risk scores. In the derivation cohort, a cut-off of 23 points identified 11,414 patients (39.1%) with a 1-year BARC 3 or 5 bleeding risk ≥4%. An alternative version of the score, including acute myocardial infarction on admission instead of white-blood-cell count, showed similar predictive ability. The PRECISE-HBR score is a contemporary, simple 7-item risk score to predict bleeding after PCI, offering a moderate improvement in discrimination over multiple existing scores. Further evaluation is required to assess its impact on clinical practice.

An aspirin-free strategy for percutaneous coronary intervention in patients with diabetes: a pre-specified subgroup analysis of the STOPDAPT-3 trial.

Safety of aspirin-free strategy immediately after percutaneous coronary intervention (PCI) for cardiovascular events in patients with diabetes was unknown. We conducted the prespecified subgroup analysis on diabetes in the STOPDAPT-3 trial, which randomly compared prasugrel (3.75mg/day) monotherapy (2984 patients) to dual antiplatelet therapy (DAPT) with prasugrel and aspirin (2982 patients) in patients with acute coronary syndrome or high bleeding risk. The co-primary endpoints were major bleeding events (Bleeding Academic Research Consortium 3 or 5) and cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or stroke) at 1 month. Of 5966 study patients, there were 2715 patients (45.5%) with diabetes. Patients with diabetes more often had chronic coronary syndrome, heart failure or cardiogenic shock, and comorbidities than those without. Patients with diabetes compared to those without had higher incidences of major bleeding and cardiovascular events. Regardless of diabetes, the effect of no-aspirin relative to DAPT was not different for the co-primary bleeding (diabetes: 5.05% versus 5.47%; HR, 0.92; 95%CI, 0.66-1.28 and non-diabetes: 3.99% versus 4.07%; HR, 0.98; 95%CI, 0.69-1.38; P for interaction=0.81) and cardiovascular (diabetes: 5.54% versus 5.15%; HR, 1.08; 95%CI, 0.78-1.49 and non-diabetes: 2.95% versus 2.47%; HR, 1.20; 95%CI, 0.79-1.82; P for interaction=0.70) endpoints. The incidences of subacute definite or probable stent thrombosis and any coronary revascularization were higher in the no-aspirin group than in the DAPT group regardless of diabetes. The effects of an aspirin-free prasugrel monotherapy (3.75mg/day) relative to DAPT for major bleeding and cardiovascular events were not different regardless of diabetes. Clinical trial registration: ShorT and OPtimal duration of Dual AntiPlatelet Therapy after everolimus-eluting cobalt-chromium stent-3 [STOPDAPT-3]; NCT04609111.

Ultrasound-Guided Venous Puncture Reduces Groin Complications in Electrophysiological Procedures.

Background: In electrophysiological procedures, multiple punctures on the femoral vein can be necessary depending on the number of catheters required. The femoral vein is typically located indirectly by using its anatomical relationship to the artery as a reference. However, this conventional approach can lead to significant complications, including bleeding, peri-interventional transfusion, pseudoaneurysms, or arteriovenous fistulas. Despite these risks, there is limited evidence comparing the safety of ultrasound-guided venipuncture versus the conventional technique in electrophysiological procedures. Objective: This study aimed to evaluate the impact of ultrasound-guided venipuncture on vascular access complications in electrophysiological procedures and to identify associated risk factors. Methods: In this single-center trial, patients scheduled for electrophysiological procedures at Ulm University Heart Center, Germany, were enrolled between November 2021 and October 2023. Venipuncture in the groin was performed using either the conventional or an ultrasound-guided approach. The primary composite endpoint was defined as peri-interventional major vascular access complications (Bleeding Academic Research Consortium (BARC) ≥2 bleeding, pseudoaneurysms, arteriovenous fistulas, and peri-interventional transfusion) and minor complications (BARC 1). Results: A total of 1370 patients were included: 749 in the conventional group and 621 in the ultrasound group. The primary endpoint was achieved in 19.2% of the conventional group and 12.1% of the ultrasound group (p < 0.001). An increased sheath diameter and a higher number of venous accesses were identified as risk factors for the primary endpoint. Conclusions: Ultrasound guidance for venous groin puncture in electrophysiological procedures reduces access-related complications, supporting its use with careful attention to sheath size and number.

Impact of ticagrelor with or without aspirin on total and recurrent bleeding and ischemic events after percutaneous coronary intervention: A sub-study of the TWILIGHT trial.

In standard time-to-first event analysis, early aspirin discontinuation followed by ticagrelor monotherapy has been shown to reduce bleeding without increasing ischemic complications compared with ticagrelor plus aspirin after percutaneous coronary intervention (PCI). We evaluated whether these treatment effects are preserved when recurrent events are considered. In this TWILIGHT trial post hoc analysis, we assessed the effects of ticagrelor monotherapy on the total number of events that occurred over the 12-month follow-up among 7 119 high-risk patients randomized to aspirin or placebo in addition to ticagrelor at 3 months post-PCI if event-free and adherent to treatment. There were 391 patients with at least one Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding (primary endpoint). Of those, 28 (7.2%) had a recurrent event. The total number of BARC 2, 3, or 5 bleeding events were 148 in the ticagrelor monotherapy arm compared with 278 with ticagrelor plus aspirin arm (p<0.001). Among 272 patients with at least one key secondary ischemic endpoint (all-cause death, myocardial infarction, or stroke), 37 (13.6%) sustained a recurrent event. Total ischemic events were similar (155vs 159) in the two groups. Among selected high-risk patients who underwent PCI and completed 3 months of dual antiplatelet therapy followed by ticagrelor with or without aspirin, recurrent bleeding was less common than recurrent ischemic events over 12 months. Analysis of total events indicates that ticagrelor monotherapy continues to be more effective than ticagrelor plus aspirin in reducing bleeding without a signal of ischemic harm.

Upper- vs Lower-Extremity Secondary Access During Transcatheter Aortic Valve Implantation

An upper-extremity approach for secondary access during transfemoral transcatheter aortic valve implantation (TAVI) may reduce clinically relevant secondary access site-related bleeding. To investigate the safety and efficacy of an upper-extremity approach compared with a lower-extremity approach in patients undergoing TAVI. The TAVI XS trial was a randomized clinical trial performed between November 28, 2022, and November 15, 2023, with a 30-day follow-up, in 4 TAVI centers in the Netherlands. Eligibility was determined first, and only those patients with severe aortic stenosis and no contraindication for upper- or lower-extremity secondary access were informed about the study and asked to participate. Participants were randomized 1:1 between the upper-extremity approach (radial artery diagnostic access and upper-arm vein for temporary pacing lead placement) and lower-extremity approach (femoral artery diagnostic access and femoral vein for temporary pacing lead placement) for secondary access during TAVI. Primary end point was clinically relevant bleeding (Bleeding Academic Research Consortium type 2, 3, or 5) of the randomized secondary access. Secondary end points included any clinically relevant bleeding, time to mobilization, duration of hospitalization, secondary access failure, and procedural time. Of a total of 324 eligible patients, 238 patients undergoing transfemoral TAVI (mean [SD] age, 79.4 [6.5] years; 150 male [63.0%]; median European System for Cardiac Operative Risk Evaluation II score, 2.2% [IQR, 1.5%-3.5%]) were included. The primary end point occurred in 5 of 119 patients (4.2%) in the upper-extremity group and 16 of 119 (13.4%) in the lower-extremity group (odds ratio [OR], 0.28 [95% CI, 0.10-0.80]; P = .01). Incidence of any clinically relevant bleeding was decreased in the upper-extremity group (25 of 119 [21.0%] vs 41 of 119 [34.5%] patients; OR, 0.51 [95% CI, 0.28-0.91]; P = .02). There was no difference in time to mobilization or duration of hospitalization. Secondary access failure (14 of 119 [11.8%] vs 1 of 119 [0.8%] patients; OR, 15.73 [95% CI, 2.03-121.69]; P = .001) and procedural time (60.0 [IQR, 39.0-88.0; 95% CI, 53.0-70.0] vs 48.0 [IQR, 34.0-64.0; 95% CI, 40.0-55.0] minutes; P = .002) were higher in the upper-extremity cohort. In this randomized clinical trial of patients undergoing transfemoral TAVI, the upper-extremity approach for secondary access was associated with less clinically relevant access site-related bleeding compared with the conventional lower-extremity approach and should be considered to reduce periprocedural bleeding complications. ClinicalTrials.gov Identifier: NCT05672823.