Antiplatelet Therapy Research Articles

Anticoagulant monotherapy versus anticoagulant therapy in combination with single antiplatelet agent in patients after coronary artery bypass grafting - analysis of real-world data

Abstract Introduction Among patients undergoing coronary artery bypass grafting (CABG), in a significant group chronic anticoagulant treatment is indicated. Current recommendations from scientific societies do not clearly indicate the optimal antithrombotic treatment strategy in this group of patients. Addition of antiplatelet therapy recommended after CABG to chronic anticoagulant therapy increases the risk of bleeding complications, however, efficacy of antithrombotic treatment strategies has not been compared in large prospective studies. Purpose The aim of the study was to compare the efficacy and safety of post-CABG antithrombotic treatment strategies in patients after CABG with coexisting indications for chronic anticoagulant treatment, based on the analysis of the real-world database. Methods Real-world data from the THIN database were analyzed. The population included adult patients from France and Great Britain undergoing CABG between 2010 and 2022 who were treated with anticoagulants within a year after CABG and who were followed for at least one year after CABG or until death. The endpoints were compared between groups of patients treated with anticoagulants in monotherapy (VKA or NOAC) (MT) and patients treated with anticoagulants (VKA or NOAC) in combination with antiplatelet agent (ASA or oral P2Y12 inhibitor) (CT). The primary efficacy endpoint was the occurrence of major adverse cardiac events (MACE), the primary safety endpoint was major bleeding and the secondary safety endpoint was death from any cause. Results A database query obtained records of 3500 patients meeting the inclusion criteria, but due to missing data, 710 patients were included in the analysis. In this group, 193 (27.2%) patients were in MT group, and 517 (72.8%) in CT group. The majority (87.0%) were men, the mean age was 72.8 (9.4) years. The MACE occurred in 19.2% patients in the MT and in 19.3% in the CT. There was no significant effect of antithrombotic treatment strategy on time to event (log-rank test p=0.553) and on risk of MACE occurrence (HR 0.89 (95% CI 0.61 - 1.31) for CT vs. MT). The major bleeding occurred in 6.2% patients in the MT and in 10.3% in the CT and no significant effect of group was observed (log-rank test p=0.170, HR 1.55 [95% CI 0.83 - 2.90] for CT vs. MT). The death from any cause occurred in 10.9% patients in the MT and in 10.1% in the CT and no significant effect of group was observed (log-rank test p=0.174, HR 0.70 [95% CI 0.42 - 1.17] for CT vs. MT). Conclusions The results indicate the comparable efficacy and safety of both antithrombotic treatment strategies: anticoagulants in monotherapy versus anticoagulants in combination with antiplatelet agent in the group of patients after CABG with coexisting indications for chronic anticoagulation.

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.

Clinical outcomes of risk score-guided dual antiplatelet therapy in patients with acute coronary syndrome who underwent percutaneous coronary intervention

Abstract Objective We aimed to investigate the effect of risk score-guided dual antiplatelet therapy (DAPT) in patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI) from real-world clinical practice in Korea. Methods 984 patients with ACS undergoing PCI with bioabsorbable-polymer everolimus eluting stent were enrolled from 20 hospitals in the multicenter, observational study. The analysis was conducted on 834 patients who took medications according to risk score-guided DAPT and were follow-up after 1 year. GRACE score and PRECISE-DAPT score were used for risk score-guided DAPT and medication for antiplatelets was conducted as follow (Figure 1). Results The mean age was 64.0 ± 10.5 years, 77.6% were men. 43.7% had acute myocardial infarction, 62.5% hypertension and 37.6% diabetes. Multivessel and left main artery disease were about in 56.2%. Trans-radial PCI was performed in 76.3%. Aspirin was taken in almost all patients (99.1%) and clopidogrel was most frequently prescribed as a DAPT (clopidogrel 64.9%, Ticagrelor 28.1%, prasugrel 6.6%). All-cause mortality and NACE (consisting of all-cause mortality, myocardial infarction, revascularization, stent thrombosis, stroke, and major/minor bleeding) were 1.2%, and 5.4% respectively at 1 year. Stent thrombosis was occurred only in 4 patients (0.5%). Bleeding complications were developed in 19 case (2.3%). Among the bleeding sites, the access site was the most common 7 (0.8%), followed by the gastrointestinal tract 4 (0.5%). Major bleeding was occurred (BARC types 3 to 5 bleeding) in 3 cases (0.4%) and BARC type 2 was most common (1.2%) (Figure 2 and Table 1). Conclusion Bleeding complications and ischemic events were very low in real-world patients with ACS undergoing PCI during 1 year follow-up, when the management was performed according to the risk scoring-guided DAPT.Figure 1Figure 2 and Table 1

Clinical characteristics and predictors of recurrence from the Australia-New Zealand Spontaneous Coronary Artery Dissection (ANZ-SCAD) registry

Abstract Background Spontaneous coronary artery dissection (SCAD) is an increasingly recognised cause of acute coronary syndrome (ACS), particularly in young women. Our understanding of SCAD remains incomplete with limited prospective data on determinants of SCAD recurrence. Purpose We aimed to describe the clinical characteristics, incidence and predictors of SCAD recurrence and major adverse cardiovascular events (MACE) in patients with SCAD from a large, multicentre registry. Methods Observational, multi-centre prospective and retrospective cohort study recruiting patients with SCAD from 23 hospitals in Australia and New Zealand. Patients aged=>18 years with SCAD and an ACS were eligible for inclusion. Prospectively recruited patients gave their informed consent while a waiver of consent was granted for retrospectively recruited patients. An independent core laboratory adjudicated invasive coronary angiography images to confirm the diagnosis of SCAD. The primary outcome was SCAD recurrence, defined as de novo spontaneous dissection with new ACS symptoms and cardiac enzyme elevation, not due to extension of the index lesion. Cox proportional hazard models were used to evaluate the association between SCAD recurrence and predefined clinical variables. Results From a total 487 patients recruited, 423 (132 prospective and 291 retrospective) patients with SCAD confirmed on core laboratory review were included for analysis. Mean age was 52.4±10.7 years, 89.7% were female and 73.1% were Caucasian. At discharge, 75.2% were on beta-blockers, 27.9% single antiplatelet and 61.9% dual antiplatelet (DAPT). At 15 (interquartile range 5-36) months median follow-up, SCAD recurrence occurred in 3.3%, with an overall MACE of 6.6%. On multivariate analysis, the presence of fibromuscular dysplasia (FMD) or other extra-cardiac vascular abnormalities [adjusted hazard ratio (HR) 5.63, 95% confidence interval (CI), 2.09-15.3, p<0.001], and past history of stroke (adjusted HR 7.99, 95% CI, 1.51-42.4, p=0.015) were associated with higher SCAD recurrence. Discharge beta-blockers was not independently associated with SCAD recurrence, while dual antiplatelet therapy that combined ticagrelor with aspirin was associated with a higher risk of recurrence (adjusted HR 2.47, 95% CI, 1.9-15.6, p=0.048). Conclusion SCAD recurrence comprised half of overall MACE in people with SCAD. The risk of SCAD recurrence was more than 5-fold higher in patients with FMD or other extra-cardiac vascular abnormalities. Dual-antiplatelet therapy that comprised ticagrelor and aspirin was associated with a higher risk of SCAD recurrence.

The clinical impact of cardiac magnetic resonance imaging upon suspected myocardial infarction with non-obstructive coronary artery disease

Abstract Background Cardiac magnetic resonance (CMR) may identify the underlying pathology in myocardial infarction with non-obstructed coronary arteries (MINOCA), however there are scant prospective data evaluating the more important measure of actual change in diagnosis and management consequent to CMR. Purpose To evaluate impact of CMR in MINOCA upon diagnosis, diagnostic certainty and management, adjudicated by treating physicians to minimise investigator bias. Methods Prospective, multi-center international pre- and post-CMR study of suspected MINOCA. Physician diagnosis, diagnostic certainty and intended management were established by questionnaire before and after CMR. The primary outcome was change in diagnosis or management. Secondary outcomes were change in diagnosis, change in management, change in diagnostic certainty, and number-needed-to-test for de-prescription of dual antiplatelet therapy (DAPT). Potential predictors of impactful CMR were evaluated by multivariable logistic regression analysis. Results 320 patients referred by 74 clinicians underwent CMR; mean age 55.6 (12.3) years, 48.1% female. CMR was conducted at median 11 days (IQR 6-19) post presentation. CMR led to change in diagnosis or management in 62.8% (95% CI 57.4% - 68.2%, p<0.0001) and significantly increased diagnostic certainty [8/10 post-CMR (5-9) vs 6/10 pre-CMR (4-7), p<0.0001]. Predictors of impactful CMR on multivariable analysis were early CMR (≤14 days), absence of atheroma on coronary angiography, significant pre-CMR diagnostic uncertainty (≤5/10), and a history of vascular disease. DAPT was deprescribed or modified to single antiplatelet in 61.7% patients. The number-needed-to-test to deprescribe DAPT was 2.6 (and 1.6 if a myocardial infarction mimic was co-suspected pre-CMR), which has important cost-benefit implications for CMR in MINOCA. Conclusions In this first prospective multi-centre study of CMR in MINOCA where diagnostic utility was adjudicated by the treating physicians, CMR was associated with frequent and significant changes in diagnosis, clinician certainty and clinical care, including frequent de-prescription of DAPT. Early CMR is to be encouraged, particularly in patients where there is significant diagnostic uncertainty and no atheroma on coronary angiography.

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<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<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.

Clinical characteristics and predictors of adverse cardiovascular events from the australia-new zealand spontaneous coronary artery dissection (ANZ-SCAD) registry

Abstract Background Spontaneous coronary artery dissection (SCAD) is an increasingly recognised cause of acute coronary syndrome (ACS), predominantly affecting women. Our understanding of SCAD remains incomplete with limited prospective data on determinants of major adverse cardiovascular events (MACE). Purpose We aimed to describe the clinical characteristics of patients with SCAD from a large, multicentre SCAD registry. We aimed to identify the predictors of MACE (defined as the composite of all-cause death, non-fatal myocardial infarction, stroke, heart failure, and revascularisation). Methods Observational, multi-centre prospective and retrospective cohort study recruiting patients with SCAD from 23 hospitals in Australia and New Zealand. Patients aged=>18 years with SCAD and an ACS were eligible for inclusion. Prospectively recruited patients gave their informed consent with a waiver of consent for retrospectively recruited patients. All invasive coronary angiography imaging was adjudicated by an independent core laboratory to confirm the diagnosis of SCAD. Cox proportional hazard analysis was used to evaluate the association between MACE and SCAD recurrence with predefined clinical variables. Results From a total 487 patients recruited, 423 (132 prospective and 291 retrospective) patients with SCAD confirmed on core laboratory review were included for analysis. Mean age was 52.4±10.7 years, 89.7% were female and 73.1% were Caucasian. Percutaneous coronary intervention (PCI) was performed in 10.6% of patients. On discharge, 64% of conservatively managed patients were on dual antiplatelet therapy (DAPT). At 15 (interquartile range 5-36) months median follow-up, the accumulated MACE rate was 6.6%. On multivariate analysis, percutaneous coronary intervention (PCI) was associated with a higher risk of MACE [hazard ratio (HR) 3.50, 95% confidence interval (CI) 1.56-7.89, p=0.002], while discharge on at least one antiplatelet medication was associated with a lower risk of MACE (HR 0.13, 95% CI, 0.05-0.36, p<0.001). In patients managed conservatively (n=353), discharge on at least one antiplatelet medication (n=337) was associated with lower MACE (HR 0.27, 95% CI 0.1-0.73, p=0.01), with no difference between single and dual antiplatelet therapy (DAPT) (p=0.74). In patients managed conservatively and on DAPT (n=226), aspirin and clopidogrel was associated with a lower risk of MACE (HR 0.31, 95% CI 0.10-0.93, p=0.038) compared with DAPT consisting of aspirin and ticagrelor (HR 3.25, 95%CI 1.07-9.85 p=0.038) on multivariate analysis. Conclusion Patients with SCAD are at significant risk of MACE. In conservatively managed patients treated with DAPT, aspirin and clopidogrel was independently associated with a lower risk of MACE than aspirin and ticagrelor

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.

Sex-differences in prescription patterns of secondary prevention pharmacotherapy in patients with acute myocardial infarction: a 20-year perspective

Abstract Background Recent studies have demonstrated sex-related differences in secondary prevention pharmacotherapy in patients with acute myocardial infarction (AMI), although guidelines recommend the same preventive approach in both women and men. Purpose This study extends earlier work by examining temporal trends of prescribing practices of secondary prevention medications using contemporary data from a long-term period in Switzerland, with particular regard to sex inequalities. Methods For the purpose of this retrospective analysis of prospectively collected data in the Acute Myocardial Infarction in Switzerland (AMIS) Plus registry, optimal medical therapy (OMT) was defined as the combination of all five guideline-recommended medications in AMI at discharge: aspirin, P2Y12 inhibitors, lipid-lowering drugs, beta blockers, and angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB). Uni- and multivariable logistic regression analyses were performed. Results A total of 34'612 patients (men n=25’913, 75%) hospitalised with AMI between 2003 and 2022 were included in the analysis. The mean age was 66±13 years and women were on average 7 years older than men. Despite having more comorbidities, women benefited less frequently from OMT than men (51% vs. 60%) across all age groups (all p<0.001), with the greatest gap occurring in patients <50 years of age. Within the 20-year study period, significant increases over time were observed in the singular prescription of all OMT components, except for beta blockers (p=0.2). This translated into a marked increase in OMT prescription irrespective of age and sex (from 36% to 60%), mainly due to greater prescription of dual antiplatelet therapy (DAPT, from 71% to 91%) and lipid-lowering drugs (LLD, from 69% to 93%). The sex-related gap in OMT disfavoring women showed a uctuating trend over the years (getting reduced from 14% in 2003 to 0.7% in 2016 to widen again to 12% in 2022) whereas there was a continuous narrowing over time regarding the combination of DAPT plus LLD, from 18% to 10% at the beginning and the end of the observation, respectively (Figure 1). In multivariable analysis, age (OR 0.99, 95%CI 0.98-0.99, p<0.001) and female sex (OR 0.90, 95%CI 0.85-0.95, p<0.001) were independent predictors of deficient OMT prescription, while the performance of percutaneous coronary intervention was identified as the strongest positive predictor favoring it (OR 4.85, 95%CI 4.49-5.24, p<0.001). Conclusion Although there has been a gradual increase in the prescription of OMT over time among both women and men, concerning sex disparities disfavoring women, and particularly young women, remained. Targeted programs to reduce sex-related differences in secondary prevention care are warranted.

Prolonged dual antiplatelet therapy in an extended Phase 3 Cardiac Rehabilitation Program following myocardial infarction

Abstract Background Prolonged dual antiplatelet therapy (P-DAPT) is recommended in selected patients beyond 12 months after myocardial infarction (MI). Several risk scores have been developed to estimate the ischemic and bleeding risk and individualize the decision-making process. Purpose We aim to analyse the factors, including ischemic and bleeding scores, associated with P-DAPT prescription in MI patients submitted to a Cardiac Rehabilitation Program (CRP). Methods Patients with ST-segment elevation MI (STEMI) or occlusion MI (OMI) who were submitted to our CRP underwent Phase 2 CRP and were prospectively included. Patients were followed in an extended Phase 3 CRP, and a follow-up visit was scheduled 12 months after hospital discharge. Baseline and follow-up clinical characteristics and treatment after the 12-months visit were registered, specifically P-DAPT. Ischemic (DAPT score) and bleeding (PRECISE-DAPT and CRUSADE scores) risk scores were retrospectively computed. Predictors of P-DAPT were studied by univariate analysis and multivariable binary logistic regression. The model was tested by area under the curve (AUC) analysis in receiver operating characteristic curves. A p<0.05 was considered statistically significant. Results The cohort comprised 78 patients (mean age 61±11 years, 84.6% male). Anterior and inferior STEMI were the most common presentations (43.6% and 47.4%, respectively). The most prevalent cardiovascular risks factors were hypercholesterolemia (85.9%), hypertension (53.8%), smoking habit (46.2%) and diabetes mellitus (23.1%). P-DAPT was prescribed in 39 (50%) patients beyond 12 months after MI, primarily combining aspirin 100mg o.d. and ticagrelor 60mg b.i.d. (n=33, 84.6%). On multivariate analysis, variables associated with P-DAPT prescription were hypertension (HR 4.92 [1.37-17.68], p=0.02), diabetes mellitus (HR 5.13 [1.09-24.09], p=0.04), multivessel disease (HR 5.54 [1.55-19.79], p=0.008), and stent diameter <3mm (HR 5.46 [1.25-23.78], p=0.02). The predictive power of the model was excellent (AUC 0.88 [0.8-0.96], p<0.001). Ischemic (DAPT score) and bleeding (PRECISE-DAPT and CRUSADE) risk scores were not associated with P-DAPT neither in continuous form nor by using their standard cutoffs (≥2, <25 and >40 points, respectively). Conclusions In a real-life cohort of MI patients undergoing extended Phase 3 Cardiac Rehabilitation, P-DAPT was prescribed in half of the population. Clinical (hypertension and diabetes mellitus) and angiographic (multivessel disease and stent diameter <3mm) variables straightforwardly predict the likelihood of receiving P-DAPT, unlike ischemic and bleeding risk scores. The clinical consequences of this management should be further explored.Prolonged DAPT in Cardiac Rehabilitation

Undiagnosed Diabetes Mellitus is an important risk factor in secondary prevention after an acute coronary syndrome and warrants active screening

Abstract Background/Introduction Previous studies have shown that patients with Diabetes Mellitus (DM) undergoing percutaneous coronary intervention (PCI) for an acute coronary syndrome (ACS) have an increased ischemic risk compared to non-diabetics. This has led to the recommendation to take DM into account when considering extended dual antiplatelet therapy (DAPT) to prevent ischemic events. Although screening for DM can simply be conducted by measuring HbA1c values, the ACS guidelines do not yet recommend to screen for DM de novo. This may lead to undertreatment. Purpose We aimed to determine the ischemic risk of previously diagnosed DM and of DM de novo compared to patients without DM in a real world ACS population. Methods We included patients from the South East (Zuid Oost) Netherlands Heart Registry (ZON-HR) undergoing PCI for ACS without using oral anticoagulants and compared outcomes between DM and non-DM patients. In a subgroup of patients without previously diagnosed DM with available HbA1c measurements at baseline, we compared outcomes between patients with or without DM de novo (HbA1c ≥48 mmol/mol). All analyses were performed using Cox regression analysis. We used multivariate analysis to adjust for known ischemic risk factors. Results Of the 2406 patients included, 426 were previously diagnosed with DM. Additional ischemic risk factors, such as a history of myocardial infarction (MI), multivessel disease and kidney disease, were significantly more often present in patients with DM. Patients with DM showed numerically more major adverse cardiac and cerebral events (MACCE). However, this was not significant (HR: 1.24, 95% CI: 0.92-1.66). All-cause mortality was higher in patients with DM at 30 days (HR: 1.51, 95% CI 1.00-2.29) and 1 year (HR: 1.55, 95% CI 1.10-2.18), which remained significant at 1 year when corrected for additional risk factors. The HbA1c values at baseline were available in 387 patients without previously diagnosed DM. In this subgroup, 69 (18%) patients showed an elevated HbA1c level of ≥48 mmol/mol. Outcomes within this subgroup are presented in table 1. Patients with de novo DM showed significant more ischemic events after one month and one year follow-up compared to patients without DM de novo. Figure 1 depicts the survival from MACCE over time in these subgroups. Conclusion In our real world population of ACS patients undergoing PCI, we found no significant difference in ischemic risk between patients with previously diagnosed DM compared to non-DM. However, all-cause mortality was significant higher in DM patients. Active screening for DM resulted in a large proportion of patients with DM de novo who showed a major increase in ischemic risk. These results demonstrate the importance of screening for DM in ACS patients undergoing PCI.

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 prognosis evaluation of guideline-directed medical therapy for type 2 acute myocardial infarction patients with acute respiratory failure

Abstract Backgrounds Type 2 myocardial infarction (T2MI) arises from an imbalance between myocardial oxygen supply and demand during acute illness such as tachyarrhythmia, hypoxia, or hypotension without acute atherothrombosis. The efficacy of guideline-directed medical therapy (GDMT) in T2MI complicated by acute respiratory failure remains uncertain. Purposes This study was aimed to assess the impact of GDMT (including dual antiplatelet therapy, statins and β-blockers) on the prognosis of patients with T2MI and acute respiratory failure. Methods The data for this study were derived from a retrospective cohort of patients admitted to and discharged from 72 secondary and tertiary hospitals between 2010 and 2023. Inclusion criteria included patients with a discharge diagnosis of T2MI and acute respiratory failure. GDMT was defined according to the ACC/AHA Class I recommendations. Patients were divided into GDMT and N-GDMT groups, with differences in clinical characteristics adjusted using propensity score matching (PSM). Primary outcome indicators were major adverse cardiac and cerebrovascular events (MACCE), while secondary outcome indicators included in-hospital mortality, cardiac mortality, non-lethal myocardial infarction, recurrent ischemic stroke, bleeding events and revascularization. Results This study comprised 898 patients in the GDMT group and 3,777 in the N-GDMT group, resulting in 888 matched pairs after PSM. Baseline data showed that patients in the GDMT group had a higher burden of pre-existing comorbidities. In terms of treatment, the GDMT group had a higher proportion of patients undergoing Percutaneous Coronary Intervention (PCI) (4.84% vs. 1.80%, p= 0.001). In-hospital mortality was significantly lower in the GDMT group (12.4% vs. 26.4%, p< 0.001).Over amedian follow-up of 1,304 days, the incidence of MACCE within 1 month was significantly lower in the GDMT group (23.1% vs. 41.3%, p< 0.001). Furthermore, the GDMT group exhibited lower all-cause mortality (52.4% vs. 60.1%, p＜0.01) and cardiac mortality (41.3% vs. 50.3%, p< 0.001) compared to the N-GDMT group, with higher rates of revascularization (3.15% vs. 1.24%, p＜0.01). There were no statistically significant differences in the incidence of bleeding BARC3 (0.45% vs. 0.45%, p=1), recurrent non-lethal myocardial infarction (0.23% vs. 0%, p =0.5) and recurrent stroke (1.46% vs. 0.79%, p =0.261). GDMT at discharge was associated with a lower risk of MACCE in unadjusted analysis (HR=0.51, 95%CI= 0.44-0.59, p＜0.01) and after adjusting for age, gender, Killip classification and comorbidities in multivariate Coxregression analysis (aHR = 0.49, 95%CI= 0.41-0.58). Conclusions Adherence to GDMT was associated with a lower incidence of MACCE during 1-month follow-up, suggesting the importance of GDMT in this patient population.Clinical characteristics of patients

An analysis of the virtual cardio-oncology research initiative (VICORI) resource: bleeding risk among cancer patients beyond 1-year post-myocardial infarction

Abstract Introduction Cardiovascular disease (CVD) and cancer are common causes of morbidity and mortality. Advancements in treatment strategies for both diseases have resulted in a growing population who live with both conditions. Myocardial infarction (MI) represents approximately 20% of all CVD admissions in cancer patients and 10% of patients who present with an acute MI have cancer. Managing MI patients with cancer require careful balancing of their ischaemic and bleeding risks. While dual antiplatelet therapy (DAPT) increases a patient’s bleeding risk, cancer patients are at further increased risk due to a range of direct and indirect cancer effects. While our recent studies demonstrated an increased bleeding risk in cancer patients in the 1st year after MI (the period of intensive APT), it is currently not known if this risk is sustained beyond this period. VICORI is the world’s first whole-country cardio-oncology research platform, linking data from the National Cancer Registration and Analysis Service, National Institute for Cardiovascular Outcomes Research and Hospital Episode Statistics [1]. We investigated the risk of bleeding among MI patients in the 2nd year post-MI, where a large majority of patients would have completed a course of DAPT, stratified by the presence or absence of cancer. Methods In this retrospective observational study, we investigated the risk of bleeding following an MI between 2006-2019, in patients with and without cancer. Cancer was defined as a diagnosis of cancer in the 1-year preceding MI. Patients who lived past the 1st year after MI were followed-up from 12 to 24 months after their MI. We used inverse probability weighting based on propensity scores to produce a balanced cohort of patients with and without cancer. Cox proportional hazard and flexible parametric modelling were used to investigate cancer as a predictor of bleeding. Subgroup analyses were performed on stent status, MI and cancer type. Results Of 506280 patients presenting with MI, 5666 (1.1%) had cancer while 500614 (98.9%) did not. Prostate (n=1377), colorectal (n=1024), lung (n=490), breast (n=448) and bladder (n=334) cancers were among the most common types of cancers. The rate (hazard) of bleeding in MI was higher in patients with cancer in the 2nd year post-MI (HR:1.42, 95%CI 1.29-1.56) compared to those without. From the flexible parametric survival analysis, the risk of bleeding in cancer patients in the 2nd year post-MI was lower compared to the 1st year but remained statistically significant compared to non-cancer patients. Conclusion In this large real-world study, cancer patients have a persistent, increased bleeding risk beyond the 1-year post-MI period, compared to those without cancer, and this risk differed by type of cancer. Further work is needed to identify specific patient characteristics in each patient sub-group which alters one’s ischaemic or bleeding risk so they can be balanced favourably with personalised strategies.

Correlation analysis of self-rated health and net adverse clinical events in patients with acute myocardial infarction

Abstract Backgrounds Self-rated health (SRH） is a recognized standard risk factor for myocardial infarction, but its impact on prognosis remains uncertain. Purpose This study aims to investigate the impact of self-rated health on the long-term clinical outcomes of myocardial infarction patients. Methods The data for this study were derived from a retrospective cohort of patients admitted to and discharged from 72 secondary and tertiary hospitals from 2010 to 2023, Patients were divided into satisfied and unsatisfied groups based on their responses to an SRH questionnaire. Propensity score matching (PSM) was utilized to balance covariates between the two groups and analyze the relationship between SRH and clinical outcomes. The primary endpoint was net adverse clinical events (NACE), comprising cardiac death, recurrent myocardial infarction, revascularization, ischemic stroke, and bleeding events (BARC ≥3). The secondary endpoint comprised the individual components of the primary endpoint. Results The study included a total of 55,054 AMI patients, with 54,049 rating their health as satisfactory and 1,005 patients as unsatisfactory. In the satisfactory group, patients tended to be younger, had fewer females, better Killip classification, a higher proportion of STEMI cases, a higher rate of undergoing PCI, and a lower prevalence of concomitant disease such as diabetes, hypertension, chronic kidney disease, cerebrovascular disease, peripheral vascular disease, thyroid disease, and chronic lung disease. Additionally, patients in the satisfactory group had a higher proportion of antiplatelet therapy use (aspirin, ticagrelor). 1,005 pairs were well matched after PSM. After a median follow-up of 1626 days, the proportion of all-cause death, cardiac death, and recurrent myocardial infarction in the satisfied group was significantly lower than that in the unsatisfied group. Multivariable Cox regression analysis revealed that satisfactory SRH was associated with a reduced risk of NACE (aHR 0.809, 95%CI 0.704-0.930, P=0.002), cardiac death (aHR 0.790, 95%CI 0.665-0.939, P=0.007), and recurrent myocardial infarction (aHR 0.734, 95%CI 0.563-0.955, P=0.021). Conclusions Good SRH can decrease the risk of NACE in myocardial infarction patients, underscoring the importance of considering SRH in clinical assessment.

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.

Combined PVI and LAAC is feasible using RFA or PFA in a canine model despite acute tissue edema in PFA versus RFA

Abstract Background Combined procedure with pulmonary vein isolation (PVI) using thermal energy followed by left atrial appendage closure (LAAC) has been used in select patient populations with positive results. Pulsed field ablation (PFA) is a novel non-thermal ablation modality that ablates cardiac tissue by irreversible electroporation. The effect of PFA on cardiac tissue and its interaction with a LAAC device in a single procedure has not been studied. Purpose To evaluate using transesophageal echo (TEE) imaging the acute tissue response following ablation by PFA compared to radiofrequency ablation (RFA) and its interaction with the WATCHMAN FLX Pro LAAC device when used in a combined procedure in a healthy canine model. Methods Nine mongrel canines underwent PVI using either circumferential PFA (FARAPULSE) energy application (n=6) or RFA energy (n=3). TEE imaging was obtained at the time of the procedure before and immediately after ablation energy application. The general appearance and echogenicity of the left lateral ridge was assessed and the os of the left atrial appendage (LAA) was measured in the four standard TEE views (0, 45, 90, and 135 degrees). Decisions about device sizing were made accordingly. PVI was evaluated by entry and exit block in all veins except the right inferior pulmonary vein (RIPV), which was not ablated. Following ablation, the LAAC device was implanted using TEE and fluoroscopic guidance in all animals and the percentage of compression measured. PASS criteria were assessed before the release of each device. All animals received dual antiplatelet therapy post implant. Results PVI was confirmed in all animals (except RIPV which was not targeted for ablation) using PFA and RFA. LAA dimensions (at device landing site) did not change substantially after RF ablation. With PFA, there was evidence of more diffuse edema and decrease in LAA diameter (Table). The LAAC device was implanted successfully after meeting PASS criteria in all animals within 30 minutes post ablation. The device size was decreased following PFA in two (2/6) animals, whereas there was no deviation from baseline measurements in device size for any of the RFA animals. Average LAAC device compression was higher for PFA versus RFA animals (Table). TEE post implant confirmed absence of any peri-device leaks in all animals. Conclusion Concomitant PVI using PFA (FARAPULSE) and LAAC (WATCHMAN FLX Pro) is feasible with 100% success and no residual acute peri-device leak. In the canine model, PFA is associated with more diffuse edema compared to RFA, which might affect device sizing. Long term consequences of this acute edema need to be evaluated in serial imaging and future larger clinical trials.Table

Remnant cholesterol is associated with platelet reactivity for patients with coronary artery disease underwent percutaneous coronary intervention

Abstract Background In recent years, remnant cholesterol has received increasing attention and has been shown to be associated with thrombotic and bleeding events in coronary clinical research, but the mechanisms are not fully understood. Aim To investigate the relationship between the remnant cholesterol (RC) and the platelet reactivity in patients with coronary artery disease undergoing percutaneous coronary intervention (PCI) who were receiving the dual antiplatelet therapy (DAPT). Methods: A total of 10,724 consecutive PCI patients in China from January 2013 to December 2013 were enrolled, among whom 6212 patients had the results of thromborlastogram (TEG) with DAPT for analysis. Low on-treatment platelet reactivity (LTPR) and high on-treatment platelet reactivity (HTPR) were defined as adenosine diphosphate-induced platelet maximum amplitude of TEG<31mm and >47mm, respectively. Results: A total of 6,212 PCI patients (mean age, 58.24±10.27 years;male, 77.5%) were finally enrolled for analysis. There were 2362 (38.02%) patients in LTPR group, and 1900 (30.59%) patients in HTPR group. For LTPR,when the RC is used as a continuous variable, the multivariate logistic regression showed that RC concentration was independently and negatively associated with LTPR (OR: 0.769, 95%CI 0.610-0.968, p=0.025). For quartiles of RC, the quartile 3 of RC was also associated with LTPR, compared with the lowest quartile (Q1) (OR: 0.854, 95%CI 0.732-0.996, p=0.044). For HTPR, when the RC is used as a continuous variable, the multivariate logistic regression showed that RC concentration was independently and positively associated with HTPR (OR: 1.492, 95%CI 1.162-1.916, p=0.002). For quartiles of RC, compared with the lowest quartile (Q1), the higher quartile of RC (Q2, Q3, Q4) was also associated with HTPR (ORQ2: 1.211, 95%CI 1.024-1.431, p=0.025; ORQ3: 1.380, 95%CI 1.165-1.634, p＜0.001; ORQ4: 1.391, 95%CI 1.143-1.692, p=0.001). Conclusions: In this large sample real-world study, we firstly reported that the lower RC concentration was an independent risk factor for LTPR, representing a higher risk of bleeding, whereas the higher RC concentration was an independent risk factor for HTPR, representing a higher risk of ischemic. These results suggest that higher or lower RC may increase the potential risk of bleeding or ischemia in patients with PCI, which provides new perspectives on individualized lipid-lowering and antithrombotic treatment strategies for patients with coronary artery disease.

Short versus conventional DAPT in patients undergoing PCI with ultra-thin DES by renal function: an analysis from the HOST-IDEA trial

Abstract Background Patients with impaired renal function are known to have an elevated risk of both ischemic and bleeding events following percutaneous coronary intervention (PCI). However, there is insufficient data available on the optimal duration of dual antiplatelet therapy (DAPT), especially with the latest generation of drug-eluting stent (DES)s. Objective We investigated to assess the efficacy and safety of abbreviated duration of DAPT in patients undergoing PCI with 3rd generation DESs based on their renal function. Methods In this prespecified subgroup analysis of the HOST-IDEA trial, a total of randomized 1997 patients with available baseline estimated glomerular filtration rate (eGFR) were categorized into three groups: high eGFR (>90 mL/min), intermediate eGFR (60 to 90 mL/min), and low eGFR (<60 mL/min). The primary outcome assessed during the 1-year follow-up period was net adverse clinical events (NACE). Ischemic and bleeding endpoints were also evaluated. Results Compared to intermediate or high eGFR groups, the low eGFR group resulted in significantly worse outcomes (P < 0.001). 3-6 month DAPT was associated with similar risk of NACE across all eGFR groups (High eGFR: HR: 0.91; 95% CI: 0.38-2.20; Intermediate eGFR: HR: 0.76; CI: 0.33-1.73; Low eGFR: HR: 0.99; CI: 0.51-1.92). There was also no significant difference in target lesion failure (HR: 0.95; CI: 0.32-2.83, HR: 0.77; CI: 0.29-2.06, and HR: 1.14; CI: 0.47-2.75) and major bleeding (HR: 0.84; CI: 0.19-3.74, HR: 0.59 CI: 0.14-2.48; and HR 0.83 CI: 0.34-2.05) among all stratified eGFR groups. This effect was also consistent in patients of end stage of renal disease (eGFR <15 mL/min). Conclusions In patients undergoing PCI with third generation DESs, short DAPT was comparable to conventional DAPT regardless of their baseline renal function.

Impact of procedural and patient-related risks on 1-year outcomes for patients with 1-month DAPT followed by P2Y12 inhibitor monotherapy after biodegradable-polymer drug-eluting stent implantation

Abstract Background While early de-escalation of dual antiplatelet therapy (DAPT) and P2Y12 inhibitor monotherapy following short DAPT are becoming standard treatments for patients after percutaneous coronary intervention (PCI), the impact of procedural and patient-related risks on clinical outcomes of PCI for patients receiving the above DAPT regimen has never been established. Purpose To evaluate the impact of procedural and patient-related risk factors on 1-year cardiovascular and bleeding outcomes in patients with 1-month DAPT followed by P2Y12 inhibitor monotherapy after biodegradable-polymer drug-eluting stent (BP-DES) implantation. Methods Using data from the multi-centre regional-wide REIWA registry, we assessed clinical outcomes according to each risk factor and compared between patients with and without either procedural or patient-related risk factors. The primary end point was net adverse clinical events (NACE), defined as a composite of cardiovascular outcomes (cardiovascular death, myocardial infarction, definite stent thrombosis, ischemic or hemorrhagic stroke) and bleeding outcomes (TIMI major or minor bleeding), which was same with that for STOPDAPT-2 trial. Procedural risk was defined as a factor of complex PCI which was previously published and included the follows: treatment of three vessels, three or more lesions, three or more stents, bifurcation with two stents, long stenting (total stent length >60 mm) and target of chronic total occlusion. Additionally, patient-related risk factors were defined as chronic kidney disease, anaemia, peripheral vascular disease, heart failure and advanced age (≧75 years). Results Among 1,202 patients treated BP-DES with 1-month DAPT, 276 patients (23.0%) had at least one procedural factors and 510 patients (42.4%) had one or more patient-related risks. Compared with each risk factor, patients with patient-related risk factor were more likely to have higher NACE rates, whereas low NACE rates were observed in patients with each procedural risk factor (Figure 1). In addition, during 1-year follow-up, patients with patient-related risk factors had a significantly higher incidence of NACE compared with patients without such risks (4.90 % vs. 1.73 %, p = 0.002) (Figure 2). However, no significant differences in NACE rates was observed between patients with and without procedural risk factors (2.54% vs. 3.24%, p = 0.555). Conclusion In patients undergoing BP-DES implantation and 1 month DAPT followed by P2Y12 inhibitor monotherapy, patient-related risk factors had an impact on 1-year clinical outcomes, while procedural risk factors no longer had small impact on those outcomes.