Dual Antiplatelet Therapy Research Articles

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.

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.

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

Role of the cardiology pharmacist in improving quality of care for patients with acute myocardial infarction based on ESC-ACCA quality indicators

Abstract Background The European Society of Cardiology-Acute Cardiovascular Care Association (ESC-ACCA) suggested the use of quality indicators (QIs) to improve quality of care for patients with acute myocardial infarction (AMI). Among these QIs are prescribing of angiotensin-converting enzyme inhibitor (ACEi) and beta blocker (BB) if left ventricular ejection fraction (LVEF) was ≤40%, and prescribing high intensity statin and dual antiplatelet therapy (DAPT) before discharging patients from the coronary care unit (CCU). Purpose To identify the role of cardiology clinical pharmacy specialist in improving quality of care for patients with AMI based on ESC-ACCA QIs. Methods A cross-sectional study was conducted at a single CCU in Iraq between January 2021 and August 2023. Patients with AMI with or without LVEF ≤40% were included in the study. Patients' profiles were reviewed to collect data about suggestions by the cardiology clinical pharmacy specialist to initiate high intensity statin, addition of a second antiplatelet therapy to keep patients on DAPT, or addition of ACEi and/or BB if LVEF ≤40%. Results Total number of patients included was 326 of whom 119 (37%) patients had LVEF ≤40%. Drug interventions by the cardiology clinical pharmacy specialist with the initiation of statin and addition of a second antiplatelet therapy to optimize DAPT for patients with AMI and initiation of ACEi and/or BB for patients with AMI and LVEF ≤40% are shown in table 1 and figure 1. Drug interventions were based on the updated ESC guidelines and agreed by the interventional cardiologists. Conclusions Role of the cardiology clinical pharmacy specialist was important in bridging gaps in the medical therapy and improving quality of care for patients with AMI and/or LVEF ≤40% by optimizing patients medications particularly for the initiation of ACEi. ACEi was initiated in about one-quarter of the patients with AMI and LVEF ≤40% based on the suggestion of the cardiology clinical pharmacy specialist and approved by the interventional cardiologists.

Temporal trends in antithrombotic therapy following transcatheter aortic valve implantation in denmark

Abstract Background A number of randomized clinical trials have examined the use of antithrombotic therapy after transcatheter aortic valve implantation (TAVI), and guidelines have changed over time. Yet, data from clinical practise patterns are lacking and it is important to evaluate adherence to guideline recommendations over time. Purpose This study aims to evaluate the temporal use of antithrombotic therapy after TAVI in Denmark. Methods A nationwide Danish cohort of patients undergoing first-time TAVI from 2008 to 2017 were identified from Danish nationwide registries. Patients were categorized into four groups according to data on prescription filling of antithrombotic therapy within a three-months period post-TAVI: i) No antithrombotic therapy, ii) single antiplatelet therapy (SAPT), iii) dual antiplatelet therapy (DAPT), or iv) anticoagulant therapy. The use of antithrombotic therapy post-TAVI was examined for each year from 2008 to 2017. Results We identified 3187 patients undergoing first-time TAVI, among whom 120 (3.8%) did not receive any antithrombotic therapy, 715 (22.4%) were prescribed SAPT, 1244 (39.0%) were on DAPT, and 1108 (34.8%) were treated with anticoagulant therapy at three months post-TAVI. Patients without antithrombotic therapy were more often men (64.2%) and were more likely to have a history of malignancy (23.3%) compared with the other treatment groups. Patients who received oral anticoagulation had a higher burden of atrial fibrillation (75.7%). The proportion of patients with atrial fibrillation remained stable over time. During the first decade of TAVI, there was a shift in the antithrombotic treatment pattern: no therapy was ranging from 1.1% to 6.6%, SAPT from 19.1% to 29.4%, while DAPT decreased from 51.0% to 31.2% and anticoagulant therapy increased from 21.6% to 39.8% (Figure 1). Conclusion During the first decade of TAVI, antithrombotic therapy patterns post-TAVI changed substantially, such that the use of dual antiplatelet therapy decreased over time, while the use of anticoagulant therapy increased. Since atrial fibrillation remained stable over time, the increase in anticoagulant therapy is most likely due to changes in guidelines for management of atrial fibrillation in 2010. These findings show the evolving treatment patterns in the first decade of TAVI, which reflects the recommendations from clinical trials and guidelines for the management of antithrombotic therapy for patients with TAVI.

Ticagrelor vs. clopidogrel in ST elevation myocardial infarction patients with hemoglobin > 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 > 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 > 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.

Ticagrelor or prasugrel versus clopidogrel in patients with coronary heart disease

Abstract Introduction Antiplatelet therapy is pivotal in the management of coronary heart disease (CHD), especially after percutaneous coronary intervention (PCI). Clopidogrel has long been the cornerstone of dual antiplatelet therapy. However, newer agents like prasugrel and ticagrelor boast of faster onset of action and greater platelet inhibition, which may translate to improved outcomes. Purpose Our hypothesis is that prasugrel or ticagrelor are superior to clopidogrel in reducing cardiovascular mortality in chronic CHD patients. Methods We conducted a retrospective cohort study using the TriNetX network database, including patients with chronic CHD on dual antiplatelet therapy. A total of 1,420,165 patients on clopidogrel and 197,783 on prasugrel or ticagrelor were identified. We assessed the primary composite endpoint of cardiovascular mortality over a 5-year follow-up period, using event-free survival as our main outcome measure. Results The 5-year follow-up data revealed a significant difference in event-free survival between the groups. Patients on prasugrel or ticagrelor had a markedly higher event-free survival rate of 83.156% compared to 73.209% for those on clopidogrel. The Log Rank test showed a confidence interval of 1.544 to 1.592 with a highly significant p-value of <0.0001. Discussion The data suggest a clear benefit of prasugrel or ticagrelor over clopidogrel for event-free survival in CHD patients. This could be attributed to the more potent antiplatelet effects of these drugs, leading to reduced thrombotic events. Given the substantial sample size and robustness of the data, the findings advocate for a paradigm shift in the choice of more potent antiplatelet agents in clinical practice. Conclusion Our analysis supports the hypothesis that prasugrel or ticagrelor are associated with significantly lower cardiovascular mortality compared to clopidogrel in patients with chronic coronary heart disease.5-year Kaplan-Meier curves for mortality

Elderly patients are hyperresponsive to potent P2Y12 inhibitors

Abstract Background Aging has recently been associated with increased basal platelet activation and adenosine diphosphate (ADP) hyperreactivity on the one hand, but decreased platelet response to thrombin receptor stimulation on the other hand in individuals without antiplatelet therapy. In the current study, we investigated platelet response to agonist stimulation in elderly patients (70 years or older) on dual antiplatelet therapy with potent P2Y12 inhibitors. Methods Platelet aggregation in response to arachidonic acid (AA), ADP, collagen, the protease-activated receptor (PAR)-1 agonist SFLLRN and the PAR-4 agonist AYPGKF was assessed by multiple electrode aggregometry in 79 prasugrel- and 77 ticagrelor-treated patients 3 days after acute percutaneous coronary intervention. Results In the overall study population (n=156), patients aged ≥70 years (n=33) had lower platelet aggregation in response to AA, ADP and SFLLRN than younger patients (all p<0.05). In prasugrel-treated patients (n=79), those aged ≥70 years (n=13) showed significantly lower platelet aggregation in response to all agonists compared to younger patients (all p<0.05). In contrast, in ticagrelor-treated patients (n=77), those aged ≥70 years (n=20) only had significantly lower ADP-inducible platelet aggregation than younger patients (p=0.03), whereas platelet aggregation in response to AA, collagen, SFLLRN and AYPGKF was similar between elderly and younger patients on ticagrelor (all p>0.05). Among patients aged ≥70 years, prasugrel-treated patients showed significantly lower platelet aggregation in response to AA, collagen and AYPGKF than those receiving ticagrelor (all p<0.05). Conclusion Patients aged ≥70 years on potent P2Y12 inhibitors exhibit increased inhibition of ADP-inducible platelet aggregation. In addition, elderly patients on prasugrel show a significantly lower response to AA, collagen, SFLLRN and AYPGKF than younger patients.Platelet aggregation prasugrel patientsPlatelet aggregation ticagrelor 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.

Body mass index and clinical outcomes in patients with diabetes and stable coronary artery disease in THEMIS

Abstract Background Physiologic changes due to extremes of body weight may affect the efficacy and tolerability of antiplatelet treatment. However, it remains unclear whether the risks and benefits of intensified antiplatelet therapy among patients with diabetes and stable coronary artery disease (CAD) are affected by body mass index (BMI). Purpose To assess the relationship between baseline BMI and major adverse cardiovascular (CV) events, and to determine if the effects of ticagrelor vs. placebo varied across the BMI spectrum, in patients with diabetes and stable CAD. Methods THEMIS was a randomized, controlled trial of 19,220 individuals aged ≥50 years with type 2 diabetes and stable CAD, randomly allocated to ticagrelor or placebo on top of aspirin. Patients with a prior myocardial infarction (MI) or stroke, or already on dual antiplatelet therapy, were excluded. The primary efficacy outcome was a composite of CV death, MI, or stroke. The primary safety outcome was TIMI major bleeding. We examined prognostic implications of BMI using 1) restricted cubic splines for the overall trends with outcomes; 2) Cox regression models with predefined BMI intervals (<25 kg/m2, 25-29.9 kg/m2, and ≥30 kg/m2) adjusted for demographic, clinical, and laboratory variables; and 3) Cox regression models for the effects of ticagrelor vs. placebo on outcomes across the spectrum of BMI values (test for interaction). A two-sided P-value <0.01 was considered statistically significant to control the overall chance of type I errors. Results BMI was available in 19,202 (99.9%) participants, with a median of 29 kg/m2 (interquartile range: 26-33). A total of 3352 (17.5%) individuals had a BMI <25 kg/m2, 7644 (39.8%) had a BMI 25-29.9 kg/m2, and 8206 (42.7%) had a BMI ≥30 kg/m2. Median follow-up was 39.9 months (range 0-57), with 1554 primary efficacy events and 306 primary safety events occurring over the course of the study. BMI was not associated with the primary efficacy or safety outcome, or with their individual components. However, BMI was significantly associated with hospitalization for heart failure (HHF) (BMI <25 kg/m2: reference; hazard ratio [HR] for BMI 25-29.9 kg/m2: 1.07, 95% confidence interval [CI], 0.82 to 1.40; HR for BMI ≥30 kg/m2: 1.41, 95% CI, 1.07 to 1.84) and with the composite of HHF or CV death (comparable estimates) after multivariable adjustment (Figure). BMI was also significantly, positively associated with serious adverse events (BMI <25 kg/m2: reference; HR for BMI 25-29.9 kg/m2: 0.99, 95% CI, 0.93 to 1.06; HR for BMI ≥30 kg/m2: 1.20, 95% CI, 1.12 to 1.29). BMI did not modify the risks and benefits of ticagrelor vs. placebo. Conclusions BMI was independently associated with the risk of HHF and the composite of HHF or CV death, but not with other efficacy or safety outcomes, in patients with stable CAD and type 2 diabetes. Ticagrelor was of similar benefit on the primary efficacy outcome vs. placebo across the full range of BMI.

Impact of different P2Y12 inhibitors in acute coronary syndrome patients with severe chronic kidney disease: insights from the CORALYS registry

Abstract Background The impact of the most potent P2Y12i ticagrelor and prasugrel after acute coronary syndrome in patients with chronic kidney disease (CKD) remains unclear. Most evidence on dual antiplatelet therapy (DAPT) comes from real-world study but is limited to glomerular filtration rate (GFR) under 60 ml/min whereas no data are available regarding patients with severe CKD (stages IV-V) Methods Consecutive patients with acute coronary syndrome (ACS) treated with percutaneous coronary intervention (PCI) and severe CKD defined as GFR under 30 ml/min not on dialysis from the CORALYS (Incidence and Predictors of Heart Failure After Acute Coronary Syndrome) registry were included. Incidence of Net Adverse Clinical Events (NACE) defined as major adverse cardiac events (MACE, a composite of cardiovascular death, myocardial infarction and unplanned revascularizations) in addition to major bleedings (classified as BARC scale 3 to 5) was our primary endpoint. Overall MACE and their single components, all bleedings, major bleedings and hospitalizations for heart failure were the secondary ones. Results Of 14699 patients in the CORALYS registry, 257 presented with severe CKD not on dialysis and had available data on antiplatelet regimen at discharge. Patients were divided into two groups according to the type of P2Y12i prescribed at discharge: 193 (75.1%) were given clopidogrel while 64 (24.9%) with ticagrelor or prasugrel. Our populaiton was predominantly male (153, 59.5%) with an average age 75.8 ± 10.9 years old. Average GFR was 21.8 ± 6.3 ml/min. Over a median follow-up of 459 days, Ticagrelor and Prasugrel were associated to lower rates of NACE compared to Clopidogrel (39.9% vs 25.0%, p=0.036). This was mainly driven by an excess of both CV mortality (31.1% vs 6.3%) and myocardial infarction (20.7% vs 9.4%) reported in the clopidogrel group. No difference was reported regarding overall bleeding events (5.7% vs 4.6% with clopidogrel and new P2Y12i respectively, p=0.81) and major bleedings (1.7% vs 4.6% with clopidogrel and new P2Y12i respectively, p=0.15). At multivariate Cox regression analysis DAPT with Ticagrelor/Prasugrel resulted independently associated with a lower risk of NACE (Adj Hr 0.41, 95%CI 0.23-0.74, p=0.003) whereas left main involvement or multivessel coronary disease led to higher risk of NACE (Adj HR 1.96 95%CI 1.21-3.18, p=0.006) Conclusions In ACS patients treated with PCI with severe CKD ticagrelor and prasugrel were associated to lower risk of NACE, MACE, CV death and myocardial infarction compared to clopidogrel. No significative difference was reported in overall and major bleedings despite a relative increase of major bleedings in the group treated with Ticagrelor or Prasugrel.

Relationship between lipoprotein(a) and endogenous fibrinolytic status in patients with STEMI

Abstract Background The risk of myocardial infarction is at least doubled in individuals with lipoprotein(a) (Lp[a]) levels >90th percentile.[1] Lp(a) may exert pro-thrombotic effects by impairing fibrinolysis. Lp(a) has a high degree of homology to plasminogen and can competitively inhibit tissue plasminogen activator (tPA)-mediated plasminogen activation and tPA-mediated clot lysis.[2] Furthermore, Lp(a) stimulates the activity of plasminogen activator inhibitor-1, the major inhibitor of the fibrinolytic system. In patients with ST-segment elevation myocardial infarction (STEMI), impaired endogenous fibrinolysis is a strong, independent risk factor for recurrent cardiovascular events,[3] but the drivers of this are not fully understood. Whether impaired endogenous fibrinolysis is related to increased Lp(a) levels in patients with STEMI, is not known. Purpose We aimed to assess the relationship between Lp(a) and endogenous fibrinolysis in patients with STEMI. Methods In a prospective, observational study, venous blood samples were drawn from patients presenting with STEMI immediately before revascularisation, after dual antiplatelet therapy but before heparin administration. Endogenous fibrinolysis was measured immediately in non-anticoagulated whole blood using the point-of-care Global Thrombosis Test, which measures the time for occlusive thrombus formation under high shear (occlusion time) and the time for spontaneous lysis of the thrombus (lysis time).[3] Assessment of Lp(a) levels, measured by particle enhanced immunoturbidimetric assay, was performed with paired plasma samples, standardized against the International Federation of Clinical Chemistry reference material SRM2B for nmol/L. Lp(a) >32 nmol/L is associated with increased risk of ischaemic heart disease. Results A total of 80 patients were included (age 64±14y, 25% females and 86% Caucasian). There was a positive correlation between Lp(a) level and lysis time (r = 0.330, P = 0.003) (Figure 1). Lysis time was significantly longer in patients with Lp(a) >32 nmol/L (2782 [1626-3683] vs. 1725 [1259-2955] s, P = 0.044). Using a cut-point of lysis time ≥2500 s previously associated with a significantly increased cardiovascular risk in patients with STEMI, we showed that Lp(a) was significantly higher in patients with lysis time ≥2500 s (40 (22-111) vs. 18 (7-73) nmol/L, P = 0.045). Table 1 shows the relationship between clinical characteristics and Lp(a) and lysis time. Lp(a) level was higher in non-Caucasian patients. There was no correlation between Lp(a) and occlusion time (r = 0.156, P = 0.168). Conclusion In patients with STEMI, longer endogenous fibrinolysis time is related to higher Lp(a) level. Raised Lp(a) levels may, in part, contribute to impaired endogenous fibrinolysis. Future studies are required to assess whether reduction in Lp(a) with novel therapies currently in phase 3 trials can favourably modulate fibrinolysis and improve clinical outcomes.Figure 1

Application of anticoagulants in the perioperative period of pci for patients with a history of atrial fibrillation and NSTEMI: a real-world, large multicenter retrospective clinical study

Abstract Backgrounds The optimal management for patients with atrial fibrillation (AF) and concomitant coronary artery disease (CAD) remains unclear, particularly regarding anticoagulants use and ischemia-bleeding balance risks. This study aims to investigate the impact of perioperative anticoagulant use on patients with AF and acute non-ST-segment elevation myocardial infarction (NSTEMI). Methods Data for this study were obtained from a retrospective cohort of patients admitted to and discharged from 72 secondary and tertiary hospitals from 2010 to 2023. A total of 150,530 patients were enrolled, including 74,373 NSTEMI patients. Patients were divided into anticoagulants and non-anticoagulants groups. A total of 1,358 patients were included in the non-anticoagulant group, and 3,541 patients were included in the anticoagulant group. Patients in each group were one-to-one matched based on propensity scores using the nearest available pair matching (PSM) method with a caliper width equal to 0.01. The primary endpoints were major adverse cardiovascular and cerebrovascular adverse events (MACCE), including cardiovascular death, recurrent myocardial infarction, and stroke. Secondary endpoints included cardiovascular death, recurrent myocardial infarction, BARC type 3 bleeding, and cerebral hemorrhage. Follow-up time points were set at 1 month,3 months, and 6 months. Multivariate Cox regression models were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI). Results After PSM matching, each group consisted of 809 patients. The anticoagulant group had a higher proportion of males, a higher prevalence of patients with a history of Percutaneous Coronary Intervention, and hyperlipidemia, while proportions of patients with Killips classification of III/IV and history of chronic kidney disease were lower. Anticoagulant use during the perioperative period significantly reduced the occurrence of MACCE at the primary endpoint at 1 month (aHR 0.57; P < 0.001), 3 months (aHR 0.57; P = 0.023), and 6 months (aHR 0.57; P < 0.001). At the secondary endpoint, anticoagulants use was associated with a lower incidence of cardiogenic death at 1 month,3 months, and 6 months (aHR 0.55; P <0.001), (aHR 0.55; P <0.001), (aHR 0.56; P <0.001), lower risk of myocardial infarction recurrence at 3 months and 6 months (aHR 0.47; P = 0.02), (aHR 0.44; P <0.001), without increasing the risk of bleeding events, including BARC type 3 bleeding and cerebral hemorrhage. Conclusion Perioperative anticoagulant use during PCI can reduce the occurrence of cardiac death, myocardial infarction, and stroke recurrence within 6 months post-surgery without increasing bleeding events in AF and NSTEMI patients. Therefore, for patients with AF, it is recommended to consider combining anticoagulant therapy with dual antiplatelet therapy during the perioperative period, if no contraindications.

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.

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.

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.

Real-world implementation of a genotype-guided p2y12-inhibitor de-escalation strategy in acute coronary syndrome patients

Abstract Background CYP2C19 genotype-guided de-escalation from ticagrelor or prasugrel to clopidogrel, may optimize the balance between ischemic and bleeding risk in ACS patients. Purpose Compare bleeding and ischemic event rates in genotyped patients versus standard care. Methods Since 2015, ACS patients in the FORCE-ACS registry received standard dual antiplatelet therapy (DAPT). Since 2021, immediate genotype-guided P2Y12-inhibitor de-escalation was applied, switching non-carriers of the loss-of-function allele CYP2C19*3 or CYP2C19*2 from ticagrelor or prasugrel to clopidogrel, while loss-of-function carriers, carrying at least one loss-of-function allele, remained on ticagrelor or prasugrel. The primary ischemic endpoint, a composite of cardiovascular mortality, myocardial infarction (MI) or stroke and the primary bleeding endpoint, BARC 2, 3, or 5 bleeding, were compared between genotyped those on standard DAPT after one year. Results Among 5,321 enrolled ACS patients, 406 underwent genotyping, compared with 4,915 non-genotyped ACS patients on standard DAPT. In the genotyped cohort, 65.3% (n=265) were non-carriers, whereas 34.7% (n=141) were loss-of-function carriers. The primary ischemic endpoint occurred in 5.2% of patients in the genotyped cohort compared to 6.9% in the standard care cohort (adjHR 0.88, 95% CI 0.56–1.38). The rate of the primary bleeding endpoint was lower in the genotyped cohort compared to the standard care cohort (4.7% vs. 9.8%; adjHR 0.50, 95% CI 0.31-0.78). Conclusion These results demonstrate the feasibility of a CYP2C19 genotype-guided P2Y12-inhibitor de-escalation strategy in a real-world ACS population. This strategy reduced bleeding events, while ischemic events were not increased as compared to a standard DAPT regime.Primary ischemic endpointBARC 2, 3 or 5 bleeding

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.

Association between preprocedural thromboembolic or bleeding events under oral anticoagulation therapy and mid-term outcomes after percutaneous left atrial appendage closure

Abstract Background Currently, no consensus has been established on the most effective antithrombotic therapy to prevent thromboembolic and bleeding events in patients undergoing percutaneous left atrial appendage closure (LAAC). Methods We retrospectively investigated the incidence of device-related thrombosis (DRT), thromboembolic events, and bleeding events in patients who underwent LAAC from September 2019 to October 2022. After categorizing patients into groups based on preprocedural thromboembolic or bleeding events under oral anticoagulation (OAC) therapy, we compared the incidence of DRT and prognosis according to the postprocedural antithrombotic therapy. Results In patients who received the conventional antithrombotic therapy (OAC with and without single antiplatelet therapy for 45 days after LAAC and dual-antiplatelet therapy from 45 days to 6 months followed by single antiplatelet therapy), preprocedural thromboembolic events despite OAC were independently associated with DRT or postprocedural thromboembolic events at the 3-year follow-up (hazard ratio [HR] 4.55; 95% confidence interval [CI] 1.32–15.6; P = 0.016), whereas preprocedural bleeding events were independently associated with postprocedural bleeding events (HR 8.01, 95% CI 1.45–58.3; P = 0.036). Continuation of OAC for 12 months among patients who developed preprocedural thromboembolic events during OAC significantly decreased the incidence of DRT or postoperative thromboembolic events (P = 0.002) with no increase in the bleeding events (P = 0.522). Conclusions Preprocedural thromboembolic and bleeding events can predict adverse events after LAAC with conventional antiplatelet-based antithrombotic therapy. Patients who develop thromboembolic events under continuous OAC may benefit from continuous OAC for 1 year after LAAC.