Risk Of Ischemic Events Research Articles

Treatment Modifications in Acute Coronary Syndrome Patients Treated with Ticagrelor: Insights from the FORCE-ACS Registry

Aims Patients presenting with acute coronary syndrome (ACS) are frequently treated with the P2Y12-inhibitor ticagrelor. Some patients prematurely discontinue ticagrelor, but the incidence of reasons for and clinical implications of treatment modification are relatively unknown. Methods and Results Data from 4,278 ACS patients (mean age: 63.6 years, 26.1% women) who were discharged on ticagrelor and enrolled in the FORCE-ACS registry between 2015 and 2020 were used. Treatment modifications were categorized as physician-recommended discontinuation, alteration, interruption, or disruption and occurred in 26.7, 20.1, 2.8, and 3.1% of patients within 12 months of follow-up (Visual Summary). Underlying reasons for treatment modification differed per type of modification. Overall, the rate of ischemic events defined as all-cause death, myocardial infarction, or stroke was 6.6% at 12 months of follow-up. Cox regression analysis using time-updated modification variables as independent variables showed that treatment interruption (adjusted hazard ratio [HR]: 2.93, 95% confidence interval [CI]: 1.48–5.79, p < 0.01) and disruption (adjusted HR: 2.33, 95% CI: 1.07–5.07, p = 0.03) were associated with an increased risk of ischemic events even after adjustment for relevant confounders. Discontinuation and alteration were not associated with increased ischemic risk. Conclusion In clinical practice, treatment modifications in ACS patients discharged on ticagrelor are common, although type and reasons for modification are heterogeneous. Treatment interruption and disruption are associated with excess cardiovascular risk.

Antiplatelet agents in patients with intermediate coronary artery stenosis and deferred revascularization

Abstract Background There is no specific recommendation regarding optimal antiplatelet therapy after deferral of revascularization in patients with established coronary artery disease. Objectives The current study investigated safety and efficacy of antiplatelet therapy in patients with intermediate coronary artery stenosis in whom revascularization was deferred based on fractional flow reserve (FFR). Methods In the Korean National Health Insurance Service database 2013-2020, we identified 4,657 patients who had intermediate coronary artery disease on angiography for which revascularization was deferred based on FFR. During this period, reimbursement criteria of FFR were patients with no previous evidence of myocardial ischemia and intermediate coronary artery stenosis (50-70%) by quantitative coronary angiography. Patients were then classified into two groups according to initiation of antiplatelet therapy after the index procedure. Primary efficacy outcome was major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause death, myocardial infarction, unplanned revascularization, and stroke, during 5 years of follow-up. Primary safety outcome was any gastrointestinal bleeding. Results After propensity score matching in a 1:1 ratio, there were 1,634 patients in antiplatelet therapy group and 1,634 in no therapy group (total N=3,268). The risk of MACCE was similar between the two groups (24.8% vs. 24.7%; adjusted hazard ratio [aHR], 0.97; 95% confidence interval [CI], 0.84-1.13; P=0.745). However, the risk of any gastrointestinal bleeding was higher in antiplatelet therapy group than no therapy group (2.2% vs. 1.2%; aHR, 2.07, 95% CI, 1.08-4.00). These results were consistently found in subgroup analyses. Conclusions In patients with intermediate coronary artery stenosis with deferred revascularization based on FFR, antiplatelet therapy was not associated with reduced risk of ischemic events but increased risk of gastrointestinal bleeding.

Association between clinical ischemic risk and thrombogenicity phenotype and their prognostic prediction in patients undergoing percutaneous coronary intervention

Abstract Introduction The CHADS-P2A2RC score has been developed to provide better prognostic precision and improved selection of at-risk patients with coronary artery disease (CAD). The linkage of this clinical ischemic risk with thrombogenicity and their prognostic implication remain still unknown. Purpose We investigated the values of thrombogenicity indices according to the CHADS-P2A2RC score and their combined prognostic prediction in CAD patients undergoing percutaneous coronary intervention (PCI). Methods In PCI-treated patients (PCI) (n=2,705), clinical ischemic risk was classified with CHADS-P2A2RC score ("high risk": ≥ 4) and thrombogenicity indices were assessed using thromboelastography (TEG). Major adverse cardiovascular events (MACEs: a composite of all-cause death, myocardial infarction, or stroke) and major bleeding were evaluated were monitored for up to 3 years. Results Compared with "low/moderate-risk group" (67.7%), "high-risk group" (32.3%) had higher platelet-fibrin clot strength (PFCS: 67.3±7.9 vs. 65.2±7.2 mm; P < 0.001) and lower fibrinolytic activity (clot lysis at 30 min [LY30]: 0.9±2.1% vs. 1.1±2.4%, P < 0.001]. The "high-risk group" showed higher rates of "high PFCS phenotype (≥ 68 mm)" (35.3% vs. 49.7%; P <0.001), MACE (HRadjusted: 1.47; 95% CI: 1.01-2.13; P = 0.045) and all-cause mortality (HRadjusted: 1.87; 95% CI: 1.14-3.07; P = 0.013) than the "low/moderate-risk group", respectively. Among the "low/moderate-risk group", "high MA phenotype" independently predicted MACE (HRadjusted: 1.51; 95% CI: 1.00-2.27; P = 0.048) and all-cause mortality (HRadjusted: 1.90; 95% CI: 1.06-3.4; P = 0.031). Likewise, this phenotype increased the risks of MACE (HRadjusted: 1.47; 95% CI: 1.01-2.13; p = 0.045) and all-cause mortality (HRadjusted: 1.87; 95% CI: 1.14-3.07; p = 0.013) in the "high-risk group" (Table 1 and Figure 1). Prognostic impact of "high MA phenotype" on major bleeding was not significantly different across the risk-group (HRadjusted: 1.02; 95% CI: 0.39-2.72; P = 0.963 in the "low/moderate-risk group" and HRadjusted: 1.08; 95% CI: 0.50-2.34; P = 0.884 in the "high-risk group", respectively). Conclusion In PCI-treated patients, CHADS-P2A2RC score was significantly associated with a worse clinical outcome and more thrombogenic profile. Regardless of the ischemic-risk group, the level of clot-strength had an addictive effect on predicting the risk of ischemic event, indicating assessment of thrombogenicity indices using TEG may enhance post-PCI risk stratification for personalized antithrombotic therapy.

Dual pathway inhibition in patients with atherosclerosis with and without heart failure: insights from the XATOA Registry

Abstract Introduction Patients with atherosclerotic cardiovascular disease (ASCVD) are at a high-risk of experiencing a major adverse cardiovascular event, with 1 in 10 individuals experiencing an event within four years (1). To address this risk of secondary cardiovascular events, there have been renewed efforts to enhance secondary prevention therapies through the application of guideline-directed medical therapy. One secondary prevention strategy is the use of dual pathway inhibition (DPI) therapy with aspirin and vascular-dose rivaroxaban (2.5mg twice daily), which simultaneously targets both the platelet activation and thrombin generation pathways. Patients with concomitant ASCVD and heart failure (HF) are a subgroup with a higher risk for ischemic events, but have not been adequately represented in recent clinical trials. Purpose To explore the risks and benefits of DPI therapy in a generalizable population of patients with concomitant ASCVD and HF. Methods The Xarelto plus Acetylsalicylic acid Treatment patterns and Outcomes in patients with Atherosclerosis (XATOA) registry is a prospective, multicentre registry of patients with either coronary artery or peripheral artery disease that were initiated on DPI (2). The primary endpoint was a composite of cardiovascular death, myocardial infarction or stroke and the safety outcome was major bleeding. Multivariable logistic regression was performed to assess the association of HF status and ejection fraction (EF) on the outcomes of interest. Results Of 5532 participants, 4022 (72.7%) had documentation of HF status. Of those 873 (21.5%) had a history of heart failure (EF >40% - 461; EF ≤40% - 181, EF unknown – 231). Over a median follow-up of 465 days (IQR – 372-576), the primary outcome occurred in 4.9% of participants with HF compared to 2.4% in those without HF (aHR 1.57 95% CI 1.02-2.41). The safety outcome was similar in patients with and without HF (0.9% versus 1.11%; aHR 0.7 95% CI 0.31-1.67). Among patients with HF, those with an EF of ≤40% demonstrated a non-significant trend towards higher rates of adverse events including MACE (8.8% versus 3.5%; aHR 1.38; 95% CI 0.59-3.22) compared to those with an EF of > 40%. Conclusion In a generalizable cohort of patients with atherosclerotic disease and HF, the use of DPI is associated with similar outcomes to those observed in recent randomised controlled clinical trials.Table 1 - Demographics by HF statusFigure 1 - MACE by HF status

Efficacy and Safety of Ticagrelor Monotherapy in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: A Retrospective Study

Background: Dual antiplatelet therapy (DAPT) is the standard treatment for percutaneous coronary intervention (PCI), but its optimal duration is controversial. Ticagrelor monotherapy has obvious advantages in reducing the bleeding risk, so this study investigated its efficacy and safety. Objective: The objective of this study was to explore the efficacy and safety of administering ticagrelor monotherapy to patients with acute coronary syndrome (ACS) undergoing PCI. Methods: This retrospective study chose 110 patients with ACS undergoing PCI from January 2022 to April 2024. In accordance with different antiplatelet therapy methods, 58 patients received DAPT of ticagrelor and aspirin, and 54 cases were included in the control group (CG) after excluding 4 cases. Meanwhile, 52 cases received ticagrelor monotherapy after 3 months of DAPT, and 49 cases were classified as the observation group (OG) after excluding 3 cases. The platelet inhibition rates, platelet aggregation functions, and adverse events before and after treatment were compared. Results: Intergroup comparison showed no significant difference in adenosine diphosphate-induced platelet inhibition rates 3 months (T1) and 6 months (T2) after operation (p = 0.129, 0.137), and the inhibition rate in OG was significantly lower than that in CG 12 months (T3) after operation (p < 0.001). At T1, T2, and T3, no significant difference in fibrinogen and prothrombin time was found (p = 0.112, 0.751, 0.590, 0.771, 0.109, 0.121). After 12-month follow-up, intergroup comparison revealed no significant difference in the incidence of ischemic events (OG vs. CG: 4.08% vs. 9.26%; p = 0.515) and a significantly lower incidence of bleeding events in OG than in CG (OG vs. CG: 4.08% vs. 18.52%; p = 0.023). Conclusion: Administering ticagrelor monotherapy after short-term DAPT (three months) to patients with ACS undergoing PCI effectively controlled the platelet inhibition rate, reduced bleeding events, and did not increase the risk of ischemic events.

Cost analysis of CYP2C19 genetic testing in percutaneous coronary intervention patients.

CYP2C19 loss of function (LOF) carriers undergoing percutaneous coronary intervention (PCI) have an increased risk of ischemic events when treated with clopidogrel. PCI patients in TAILOR-PCI were randomized to clopidogrel or genotype-guided (GG) therapy in which LOF carriers received ticagrelor and non-carriers clopidogrel. Direct medical costs associated with a GG approach have not been described before. TAILOR-PCI participants for whom direct medical costswere available for the duration from the date of PCI to one-year post PCI were included. Primary cost estimates were obtained from the Mayo Clinic Cost Data Warehouse. There were no differences in direct medical costs between the GG and clopidogrel groups (mean $20,682 versus $19,747, p = 0.11) however total costs were greater in the GG group (mean $21,245 versus $19,891, p = 0.02) which was primarily driven by ticagrelor costs. In conclusion the increased expense of a GG strategy post PCI as compared to clopidogrel for allis primarily driven by the cost of ticagrelor.

Physiological provocation compared to acetazolamide in the assessment of cerebral hemodynamics: a case report

BackgroundSevere large vessel disease may lead to cerebral hemodynamic failure that critically impairs cerebral blood flow (CBF) regulation elevating the risk of ischemic events. Assessment of the condition is often based on changes in CBF during vasodilatation; however, pharmacologically induced vasodilation does not reflect the physiological condition during an ischemic event caused by hemodynamic failure. We compared a [15O]H2O PET brain scan during vasodilation to a [99mTc]HMPAO SPECT brain scan during an ongoing transient ischemic attack (TIA).Case presentationA single patient presenting with limb-shaking TIA underwent CT, Digital Subtraction Angiography, and two different modalities of cerebral perfusion scans: [15O]H2O PET and [99mTc]HMPAO SPECT. Acetazolamide was used in the PET scan to induce vasodilatation, and during the SPECT scan physiological stress, standing up rapidly, was used to induce limb-shaking TIA. CT-angiography and Digital Subtraction Angiography revealed an occlusion in the distal part of the right A2 segment of the anterior cerebral artery, with a corresponding infarction in the watershed area. Collaterals supplied the main vascular territory of the anterior cerebral artery. During rest, neither perfusion modalities demonstrated reduced perfusion outside of the ischemic core. However, we found a pronounced difference between the PET utilizing acetazolamide and the SPECT during the TIA. The PET scan demonstrated relative hypoperfusion in vascular territory supplied by collaterals, while the area around the ischemic core was not affected. Contrary, the SPECT had only minor relative hypoperfusion in the collateral-supplied area, whereas the watershed area proximal to the infarct core had pronounced relative hypoperfusion.ConclusionsThe observed discrepancy in compromised areas during physiological provocation compared to pharmacological induced vasodilation questions the use of an unphysiological stressor for assessment of cerebrovascular hemodynamics. A physiological provocation test may achieve more clinically relevant evaluation.

Ticagrelor monotherapy in ST-elevation myocardial infarction: An individual patient-level meta-analysis from TICO and T-PASS trials.

Patients with ST-elevation myocardial infarction (STEMI) tend to be excluded or under-represented in randomized clinical trials evaluating the effects of potent P2Y12 inhibitor monotherapy after short-term dual antiplatelet therapy (DAPT). Individual patient data were pooled from randomized clinical trials that included STEMI patients undergoing drug-eluting stent (DES) implantation and compared ticagrelor monotherapy after short-term (≤3months) DAPT versus ticagrelor-based 12-month DAPT in terms of centrally adjudicated clinical outcomes. The co-primary outcomes were efficacy outcome (composite of all-cause death, myocardial infarction, or stroke) and safety outcome (Bleeding Academic Research Consortium type 3 or 5 bleeding) at 1 year. The pooled cohort contained 2,253 patients with STEMI. The incidence of the primary efficacy outcome did not differ between the ticagrelor monotherapy group and the ticagrelor-based DAPT group (1.8% versus 2.0%; hazard ratio [HR]= 0.88; 95% confidence interval [CI]= 0.49-1.61; p= 0.684). There was no difference in cardiac death between the groups (0.6% versus 0.7%; HR= 0.89; 95% CI= 0.32-2.46; p= 0.822). The incidence of the primary safety outcome was significantly lower in the ticagrelor monotherapy group (2.3% versus 4.0%; HR= 0.56; 95% CI= 0.35-0.92; p= 0.020). No heterogeneity of treatment effects was observed for the primary outcomes across subgroups. In patients with STEMI treated with DES implantation, ticagrelor monotherapy after short-term DAPT was associated with lower major bleeding without an increase in the risk of ischemic events compared with ticagrelor-based 12-month DAPT. Further research is necessary to extend these findings to non-Asian patients. This study was funded by Biotronik (Bülach, Switzerland).

Comprehensive Analysis of Anticoagulant Therapy in Patients with Isolated Atrial Flutter

Limited comparative data exist regarding the risk of cardiogenic emboli in patients with isolated atrial flutter (AFL). Some studies suggest a lower complication risk in AFL compared to atrial fibrillation (AFib), but methodological limitations and conflicting reports necessitate a comprehensive investigation. Our analysis proposes that isolated AFL carries a lower risk of ischemic events and left atrial thrombus formation than AFib. Importantly, we caution against applying stroke risk assessment approaches designed for AFib to AFL patients, as it may lead to harmful overestimations and unnecessary anticoagulant prescriptions. Furthermore, we highlight the current lack of sufficient data to determine the overall clinical benefit of prolonged anticoagulant therapy in patients with isolated AFL, especially when CHA2DS2-VASc index values are below 4. This review challenges existing perceptions, offering insights into the nuanced risk profiles of the transitional nature of isolated AFL due to the high incidence of AFib development within a year of AFL diagnosis. In conclusion, tailored risk assessments and further research are essential for precise clinical decision-making in this dynamic landscape.

Pharmacogenomic Polygenic Model of Clopidogrel Predicts Recurrent Ischemic Events in Chinese Patients With Coronary Artery Disease

Patients with coronary artery disease (CAD) need to take antiplatelet drugs regularly in order to prevent thrombosis; however, there is existing inter-individual variability in drug response. Pharmacogenomic studies indicate that drug response may also be influenced by genetic variants, and multiple genetic variants may work together. We assumed that patients carrying more risk alleles might have a worse clopidogrel drug response and that a polygenic model integrated different single variants might have the potential to explain clopidogrel drug response variability better. We aimed to investigate whether the polygenic model could be used to predict clopidogrel drug response. A total of 935 CAD patients were enrolled in the study. We investigated the association between 19 clopidogrel-related single-nucleotide polymorphisms (SNPs) and the incidence of recurrent ischemic events. Additionally, a polygenic model was constructed to assess the risk of ischemic events. There were only 2 SNPs of CYP2C8 gene (rs1934980 and rs17110453) that were nominally associated with incidence of recurrent ischemic events. We constructed a polygenic model integrated with 6 clopidogrel-related SNPs. When compared with patients carrying 6 or fewer risk alleles, patients with 7 or more risk alleles had a higher risk of ischemic events (hazard ratio = 1.87; P = 0.04). The polygenetic model may be useful for clopidogrel drug response prediction in patients with CAD.

COVID-19 Inpatient Caseloads in General Hospitals Did Not Affect Quality Indicator Compliance Rates in Israel.

Early in the global COVID-19 pandemic, a concern was raised that potentially high volumes of COVID-19 inpatients in general hospitals might compromise the hospitals' capabilities to maintain high-quality care for routine patients and, thereby, to comply with indicators specifying quality of care. The objective of this study is to evaluate the impact of the surges of COVID-19 inpatients into general hospitals in Israel on the compliance rates for selected quality indicators reported by these hospitals within the Israeli National Program for Quality Indicators (NPQI). Compliance rate data were collected from the quality indicators reports made to the NPQI by participating hospitals. COVID-19 inpatient volume data were obtained from the Ministry of Health Digital Technologies and Data Division. Both datasets were analyzed on a week-by-week basis and plotted one alongside the other on a time scale. Association of each quality indicator's compliance rate with the number of COVID-19 inpatients was tested by Pearson's correlation analysis. The study included data from July 1, 2019 through June 30, 2022, spanning the duration of the COVID-19 pandemic in Israel. Five quality indicators included in the study were: Surgical repair of femoral neck fracture within 48h of admission; Assessment of cerebral ischemic event risk for patients with atrial fibrillation; Duplex carotid ultrasound within 72h of emergency department admission for patients with suspected transient ischemic attack; Antibiotic prophylaxis for caesarean sections; and Percutaneous coronary intervention within 90min for patients presenting with ST-elevation myocardial infarction. Compliance rates for five quality indicators, representing different aspects of routine health care, remained steady - even at times with high volumes of COVID-19 inpatients in general hospitals. This lack of effect was prominent throughout the analyzed period, i.e., general hospitals maintained similar compliance rates for all quality indicators both during the surges of COVID-19 patients and between these periods. Statistical analysis showed no correlation between the quality indicators' compliance rates and the number of COVID-19 inpatients. Our findings indicate that high volumes of COVID-19 inpatients in general hospitals did not affect the hospitals' capability to comply with routine health care quality indicators. The results of our study imply that general hospitals in Israel were able to withstand the challenges associated with the care of COVID-19 inpatients while preserving high quality of care for routine patients.

Socio-economic determinants of risk of ischemic events: results of three-year clinical and epidemiological surveillance

Socio-economic determinants of risk of ischemic events: results of three-year clinical and epidemiological surveillance

The significance of ultrasonographic characteristics in the comprehensive radiological assessment of «high risk» carotid stenoses

Background. The prevalence of asymptomatic carotid stenosis (ACS) requires the existence of an algorythm to identify patients at risk of ischemic stroke. Assessment of carotid atherosclerotic plaque (AP) based on its morphology and composition in addition to the quantitative parameter «stenosis» is possible using a complex of radiological studies including ultrasonographic ones, that can be deepened by new ultrasound techniques. Purpose – define ultrasonographic criteria for vulnerable carotid plaque based on evaluation of plaque characteristics using current ultrasonic techniques. Materials and methods. The study is based on the analysis of data obtained from 105 patients aged 41 to 84, diagnosed with stenosis of the internal carotid artery (ICA) according to ultrasonography (US). Examination methods – clinical, duplex US with the inclusion of shear wave elastography (SWE) and superb microvascular imaging (SMI) techniques to assess plaque stiffness and plaque microvascularisation; brain MRI, MSСT angiography (MSCTA), statistical. Two age-matched group were formed: a group with symptomatic carotid stenosis (SCS), 55 patients, and a group with asymptomatic carotid stenosis (ACS), 50 patients. Results. Statistically significant differences in the groups of patients with and without stroke were determined according to the following parameters of carotid plaques: quantitative criteria – maximum thickness (p = 0,02), with an AP thickness of more than 3.5 mm, the risk of stroke increases 2.2 times (p = 0,03), stenosis degree according to the NASCET protocol (p = 0,01 in the right ICA), plaque stiffness indicator according to SWE data (p = 0,001); qualitative criteria – type of plaque echogenicity according to the Gray-Weale classification (p = 0,001), presence of microvascularization according to SMI data (p = 0,04). Correlation of AP stiffness indicators according to SWE and MSCTA data (ρ = 0,60; р = 0,004) was established, as well as between AP stiffness according to SWE data and echo- type of AP (τ = 0,56; р = 0,006). Conclusions. Determination of plaque thickness greater than 3.5 mm, low plaque stiffness according to SWE data, the presence of microvascularization according to SMI data it is advisable to add to the complex of radiological assessment of carotid stenosis with a high risk of ischemic events, in addition to the standard US criteria of stenosis degree and AP echo-type.

Efficacy of P2Y12 receptor inhibitors in myocardial infarction in individuals carrying different CYP2C19 genotypes living in the northern region of Russia

Aim. To evaluate the efficacy of P2Y12 receptor inhibitors (clopidogrel and ticagrelor) in patients with myocardial infarction (MI) living in the northern region of Russia (Khanty-Mansi Autonomous Okrug — Yugra), depending on the carriage of various CYP2C19 allelic variants.Material and methods. This prospective observational study included 218 patients with acute MI who underwent percutaneous coronary intervention (PCI). The patients also underwent determination of allelic variants of the CYP2C19 gene. Patient were divided into groups receiving clopidogrel (n=164, 75%) and ticagrelor (n=54, 25%). Using biostatistical analysis methods, a comparison of clinical and genetic characteristics was performed, as well as an assessment of the risk of ischemic events between the groups in the long-term (108 months, 9 years) post-infarction period.Results. Reduced (*1/*2, *2/*2, *1/*3) and increased (*1/*17, *17/*17) metabolizer CYP2C19 genotypes, as well as severe comorbidity, are reliable independent predictors of composite outcome (cardiovascular death, recurrent acute coronary syndrome, coronary stent/bypass thrombosis, myocardial revascularization, acute ischemic cerebrovascular accident) during a long-term (9 years) follow-up. The advantages of ticagrelor over clopidogrel in terms of the effect on the incidence of ischemic events in the long-term period were established without a significant difference for bleeding both in the general cohort of patients and among carriers of CYP2C19 allelic variants (*1/*2, *2/*2, *1/*3) and (*1/*17,*17/*17) in patients with MI.Conclusion. Ticagrelor is significantly more effective than clopidogrel in reducing the risk of ischemic events in the general cohort of patients, as well as in carriers of reduced (*1/*2, *2/*2, *1/*3) and increased (*1/*17, *17/*17) metabolizer CYP2C19 genotypes during 9-year follow-up after the index MI.

PREVALENCE OF ELEVATED LOW DENSITY LIPOPROTEIN CHOLESTEROL (LDL–C) LEVELS IN ADULT PATIENTS WITH COMPLEX CONGENITAL HEART DISEASE

Abstract Background Thanks to advances in both medical care and surgical techniques, survival for adult patients with congenital heart disease (ACHD) has significantly increased over recent years, with about 90% of them now reaching adulthood. However, as CHD patients grow older, their relative risk of developing coronary artery disease (CAD) increases. Elevated low–density lipoprotein cholesterol (LDL–C) levels play a pivotal role in the genesis of CAD in the general population. Limited data exist on the prevalence of hyperlipidemia in the ACHD population. Patients with complex CHD should be considered at increased risk for CAD, mainly related to to the severity of the CHD and aging. For this reason, it could be reasonable to apply targets used for patients at high risk of CAD. Our study aimed at describing the overall prevalence of elevated LDL–C levels in a contemporary cohort of adult patients with complex CHD. Materials and Methods This is a single–centre retrospective study. All adults with complex CHD who attended the outpatient clinic at our tertiary centre from January 2000 to April 2023 were included. Demographic, clinical and laboratory data were obtained in all patients from medical records and our dedicated databases. Results A total of 230 patients with complex CHD were included in the present study (mean age 35±11 years, 124 male, mean follow up of 117±80 months). One hundred forty–three (63%) of them showed biventricular physiology, whereas 86 (37%) patients showed univentricular heart physiology. Eighty patients from our cohort underwent Fontan operation. Twenty patients (9%) showed oxygen saturation at rest lower than 90%. Mean levels of LDL–C was 87±28 mg/dl, with 184 patients (78%) showing LDL–C levels ≥ 55 mg/dl. Conclusion Our study demonstrated that, despite their relatively younger age, elevated LDL–C levels are not uncommon in patients with severe CHD. ACHD patients with complex anatomy, such as patients after Fontan operation, should be considered at increased risk of ischaemic events and treated accordingly. Further research and international collaboration are therefore paramount to understand whether and if these patients should be treated with lower lipid drugs as for the general population.

Discharge of Acute Coronary Syndrome Patients on Sub-Optimal Dual Anti-Platelet Therapy: A Single Center Experience.

To identify and quantify the reasons why acute coronary syndrome (ACS) patients undergoing stenting at the University of New Mexico Hospital (UNMH) were prescribed sub-optimal dual antiplatelet therapy (DAPT) at discharge, and to identify practice patterns that could potentially lead to improved DAPT treatment for these patients. We reviewed electronic medical records and cardiac catheterization records of 326 patients who underwent percutaneous coronary intervention (PCI) at UNMH between January 1, 2021, and June 30, 2022 and identified 229 ACS patients who survived until discharge. Demographic and clinical characteristics relevant to P2Y12 inhibitor selection were obtained from a review of medical records. Pharmacists' notes documenting their efforts to secure appropriate insurance coverage and reasons for discharging patients on clopidogrel rather than ticagrelor/prasugrel were reviewed. Patients discharged on aspirin and clopidogrel underwent review of medical records and cardiac catheterization lab records to determine if the discharge P2Y12 drug was appropriate. Reasons for inappropriate discharge on clopidogrel were categorized as cost/insurance, patient preference, concern for daily adherence to a twice-daily medication, and maintenance of pre-hospital clopidogrel therapy rather than switch to ticagrelor after PCI. The 229 ACS patients included 87 (38.0%) appropriately discharged on ticagrelor/prasugrel, 63 (27.5%) appropriately discharged on clopidogrel, 75 (32.8%) discharged on sub-optimal clopidogrel, and 4 (1.7%) not discharged on a P2Y12 inhibitor. For patients inappropriately discharged on clopidogrel (n = 75), the most common reasons were cost or lack of insurance (n = 56) and clinical inertia (taking clopidogrel before PCI and maintained on it afterward) (n = 17). Sub-optimal P2Y12 therapy at discharge was significantly associated with lack of insurance (odds ratio 21.5, 95% confidence interval 5.33-156,p < 0.001) but not with ethnicity, age, sex, or diabetes. At the University of New Mexico, a safety-net hospital, increasing financially restricted access to ticagrelor/prasugrel could help up to 24.5% of ACS patients reduce their risk of ischemic events. For patients admitted on clopidogrel DAPT, escalating to ticagrelor/prasugrel could reduce ischemic risk in 7.4%. Expanding and improving healthcare insurance coverage might reduce the frequency of discharge on sub-optimal P2Y12 therapy.

Is CYP2C Haplotype Relevant for Efficacy and Bleeding Risk in Clopidogrel-Treated Patients?

A recently discovered haplotype-CYP2C:TG-determines the ultrarapid metabolism of several CYP2C19 substrates. The platelet inhibitor clopidogrel requires CYP2C19-mediated activation: the risk of ischemic events is increased in patients with a poor (PM) or intermediate (IM) CYP2C19 metabolizer phenotype (vs. normal, NM; rapid, RM; or ultrarapid, UM). We investigated whether the CYP2C:TG haplotype affected efficacy/bleeding risk in clopidogrel-treated patients. Adults (n = 283) treated with clopidogrel over 3-6 months were classified by CYP2C19 phenotype based on the CYP2C19*2*17 genotype, and based on the CYP2C19/CYP2C cluster genotype, and regarding carriage of the CYP2:TG haplotype, and were balanced on a number of covariates across the levels of phenotypes/haplotype carriage. Overall, 45 (15.9%) patients experienced ischemic events, and 49 (17.3%) experienced bleedings. By either classification, the incidence of ischemic events was similarly numerically higher in PM/IM patients (21.6%, 21.8%, respectively) than in mutually similar NM, RM, and UM patients (13.2-14.8%), whereas the incidence of bleeding events was numerically lower (13.1% vs. 16.6-20.5%). The incidence of ischemic events was similar in CYP2C:TG carries and non-carries (14.1% vs. 16.1%), whereas the incidence of bleedings appeared mildly lower in the former (14.9% vs. 20.1%). We observed no signal to suggest a major effect of the CYP2C19/CYP2C cluster genotype or CYP2C:TG haplotype on the clinical efficacy/safety of clopidogrel.

Clinical Impact of Dyspnea after Ticagrelor Treatment and the Effect of Switching to Clopidogrel in Patients with Myocardial Infarction.

Dyspnea is frequent during ticagrelor-based dual antiplatelet therapy (DAPT) for acute myocardial infarction (AMI). However, its clinical characteristics or management strategy remains uncertain. The study assessed 2,617 AMI patients from the Ticagrelor versus Clopidogrel in Stabilized Patients with AMI (TALOS-AMI) trial. Dyspnea during 1-month ticagrelor-based DAPT and following DAPT strategies with continued ticagrelor or de-escalation to clopidogrel from 1 to 12 months were evaluated for drug adherence, subsequent dyspnea, major adverse cardiovascular events (MACE), and bleeding events. Dyspnea was reported by 538 patients (20.6%) during 1 month of ticagrelor-based DAPT. Adherence to allocated DAPT over the study period was lower in the continued ticagrelor arm than the de-escalation to clopidogrel, particularly among the dyspneic population (81.1% vs. 91.5%, p < 0.001). Among ticagrelor-treated patients with dyspnea, those switched to clopidogrel at 1 month had a lower frequency of dyspnea at 3 months (34.3% vs. 51.7%, p < 0.001) and 6 months (25.5% vs. 38.4%, p = 0.002) than those continued with ticagrelor. In patients with dyspnea in their 1-month ticagrelor-based DAPT, de-escalation was not associated with increased MACE (1.3% vs. 3.9%, hazard ratio [HR]: 0.31, 95% confidence interval [CI]: 0.08-1.11, p = 0.07) or clinically relevant bleeding (3.2% vs. 6.2%, HR: 0.51, 95% CI: 0.22-1.19, p = 0.12) at 1 year. Dyspnea is a common side effect among ticagrelor-based DAPTs in AMI patients. Switching from ticagrelor to clopidogrel after 1 month in AMI patients may provide a reasonable option to alleviate subsequent dyspnea in ticagrelor-relevant dyspneic patients, without increasing the risk of ischemic events (NCT02018055).

Individualized antiplatelet therapy for non-cardiogenic ischemic stroke

ObjectiveThis research aims to investigate the impact of individualized antiplatelet therapy guided by thromboelastography with platelet mapping (TEG-PM) on the clinical outcomes of patients with non-cardiogenic ischemic stroke. MethodsAmong a total of 1264 patients, 684 individuals diagnosed with non-cardiogenic ischemic stroke underwent TEG-PM testing. Based on the adjustment of antiplatelet medication, these patients were divided into individual and control groups. Within the individual group, in accordance with the TEG-PM test results, a Maximum amplitude (MA) value greater than 47mm was defined as high residual platelet reactivity (HRPR), while an MA value less than 31mm was defined as low residual platelet reactivity (LRPR). Patients with arachidonic acid (AA) less than 50% and adenosine diphosphate (ADP) less than 30% were classified as aspirin-resistant or clopidogrel-resistant. Treatment strategies for antiplatelet medication were subsequently adjusted accordingly, encompassing increment, decrement, or replacement of drugs. Meanwhile, the control group maintained their original medication regimen without alterations. ResultsThe individual group included 487 patients, while the control group had 197. In the individual group, approximately 175 patients (35.9%) were treated with increased medication dosages, 89 patients (18.3%) with reduced dosages, and 223 patients (45.8%) switched medications. The results showed that the incidence rate of ischemic events in the individual group was lower than that of the control group (5.54% vs. 12.6%, P = 0.001), but no significant difference was observed in bleeding events. Cox regression analysis revealed age (hazard ratio, 1.043; 95% CI, 1.01-1.078; P = 0.011) and coronary heart disease (hazard ratio, 1.902; 95% CI, 1.147-3.153; P = 0.013) as significant risk factors for adverse events. ConclusionIndividualized antiplatelet therapy based on TEG-PM results can reduce the risk of ischemic events in patients with non-cardiogenic ischemic stroke without increasing the risk of bleeding events or mortality. Advanced age and coronary heart disease were identified as risk factors affecting the outcomes of individualized antiplatelet therapy.

The Association of CHADS-P2A2RC Risk Score With Clinical Outcomes in Patients Taking P2Y12 Inhibitor Monotherapy After 3 Months of Dual Antiplatelet Therapy Following Percutaneous Coronary Intervention.

Concerns remain that early aspirin cessation may be associated with potential harm in subsets at high risk of ischemic events. This study aimed to assess the effects of P2Y12 inhibitor monotherapy after 3-month dual antiplatelet therapy (DAPT) vs. prolonged DAPT (12-month or longer) based on the ischemic risk stratification, the CHADS-P2A2RC, after percutaneous coronary intervention (PCI). This was a sub-study of the SMART-CHOICE trial. The effect of the randomized antiplatelet strategies was assessed across 3 CHADS-P2A2RC risk score categories. The primary outcome was a major adverse cardiac and cerebral event (MACCE), a composite of all-cause death, myocardial infarction, or stroke. Up to 3 years, the high CHADS-P2A2RC risk score group had the highest incidence of MACCE (105 [12.1%], adjusted hazard ratio [HR], 2.927; 95% confidence interval [CI], 1.358-6.309; p=0.006) followed by moderate-risk (40 [1.4%], adjusted HR, 1.786; 95% CI, 0.868-3.674; p=0.115) and low-risk (9 [0.5%], reference). In secondary analyses, P2Y12 inhibitor monotherapy reduced the Bleeding Academic Research Consortium (BARC) types 2, 3, or 5 bleeding without increasing the risk of MACCE as compared with prolonged DAPT across the 3 CHADS-P2A2RC risk strata without significant interaction term (interaction p for MACCE=0.705 and interaction p for BARC types 2, 3, or 5 bleeding=0.055). The CHADS-P2A2RC risk score is valuable in discriminating high-ischemic-risk patients. Even in such patients with a high risk of ischemic events, P2Y12 inhibitor monotherapy was associated with a lower incidence of bleeding without increased risk of ischemic events compared with prolonged DAPT. ClinicalTrials.gov Identifier: NCT02079194.