Search Results (65)

Background: Ticagrelor is a reversible, direct inhibitor of the platelet adenosine diphosphate (P2Y12) receptor, widely used in combination with acetylsalicylic acid (ASA) as dual antiplatelet therapy (DAPT) in patients with acute coronary syndrome (ACS) to prevent cardiovascular events. Despite its well-established efficacy, ticagrelor may cause adverse effects ranging from common ones (e.g., bleeding, dyspnea) to rare but potentially serious reactions such as bradyarrhythmias. These rare events are likely related to elevated adenosine levels secondary to inhibition of the human equilibrative nucleoside transporter 1 (hENT1). Methods: We describe two clinical cases of ticagrelor-associated bradyarrhythmia observed in patients following ACS. Both cases were analyzed in terms of clinical presentation, ECG findings, management strategy, and outcomes after discontinuation of the drug. Results: The first case concerns a 67-year-old woman with non-ST-segment elevation myocardial infarction (NSTEMI) who developed complete atrioventricular block (third degree) with a 45 s asystolic pause and syncope. The second case involves a 67-year-old man with anterior ST-segment elevation myocardial infarction (STEMI) who experienced recurrent sinus pauses lasting up to 5 s. In both cases, symptoms resolved following ticagrelor discontinuation and theophylline administration. No recurrence of arrhythmia was observed after switching to prasugrel. Conclusions: Ticagrelor-induced bradyarrhythmias, although rare, represent an important and reversible adverse effect that clinicians should be aware of, particularly during the early post-ACS phase. Prompt recognition and drug withdrawal may prevent severe outcomes and avoid unnecessary interventions such as pacemaker implantation. Further studies are warranted to identify patient-specific risk factors predisposing to ticagrelor-related conduction disturbances. Full article

Background: Dual antiplatelet therapy (DAPT), combining aspirin with a P2Y12 receptor inhibitor (P2Y12i), remains central to the management of acute myocardial infarction (MI), especially in patients undergoing percutaneous coronary intervention (PCI). However, the pharmacodynamic response to antiplatelet therapy may vary with body composition. This study investigates the association between body mass index (BMI) and clinical outcomes in MI patients treated with PCI and DAPT. Methods: This retrospective cohort study analyzed data from 52,119 MI patients treated with coronary stenting from 2014 to 2021, sourced from the Hungarian Myocardial Infarction Registry. Patients were stratified into clopidogrel-based (n = 44,480) and potent P2Y12i-based (prasugrel or ticagrelor; n = 7639) DAPT cohorts. Clinical outcomes—including 12-month mortality and ischemic events—were assessed across BMI categories. Kaplan–Meier analysis and LASSO Cox regression identified predictors of mortality, while decision curve analysis (DCA) evaluated the net clinical benefit of potent P2Y12i across BMI strata. Results: Univariate and multivariate Cox regression analyses identified BMI and potent P2Y12i treatment as significant predictors of 365-day mortality, with higher BMI associated with lower observed rates of mortality, major adverse cardiovascular events (MACEs), and stroke. However, higher BMI was also associated with an increased risk of repeat revascularization and PCI. This study found that the protective effect of potent P2Y12i treatment was consistent across different BMI categories. Conclusions: In patients with MI undergoing PCI, elevated BMI was paradoxically associated with more favorable short-term outcomes, including reduced mortality. Potent P2Y12i therapy demonstrated a consistent benefit across BMI categories, supporting its broad application irrespective of body mass. Full article

Background/Objectives: Patients that undergo percutaneous coronary intervention (PCI) require effective antiplatelet therapies to minimize the risk of thrombotic cardiovascular events. Oral P2Y12 inhibitors are often utilized, however co-administered opioids may lead to gastric absorption issues in these patients, affecting the efficacy of oral inhibitors. Cangrelor is an intravenous, direct-acting, reversible P2Y12 inhibitor that could be explored as a potential treatment option for patients with gastric absorption issues during ST-elevation myocardial infarction. The objective was to estimate the UK budget impact of introducing cangrelor for ST-elevation myocardial infarction (STEMI) patients with gastric absorption issues undergoing PCI. Methods: A budget impact model was developed to calculate the impact of introducing cangrelor to treat STEMI patients with gastric absorption issues undergoing PCI, to the UK National Health Service and personal social services, over 5 years. Oral P2Y12 inhibitors (clopidogrel, prasugrel, and ticagrelor), glycoprotein IIb/IIIa inhibitors (eptifibatide and tirofiban), and aspirin and heparin alone were included as base case comparators. Cangrelor uptake ranged from 10% to 30% in years 1–5. The cangrelor-eligible population was estimated at 10,903 patients per year. Results: Over 5 years, cangrelor leads to a small cost saving (0.29%), varying from −GBP 261,989 in year 1 to GBP 174,778 in year 5. The introduction of cangrelor is estimated to lead to 314 fewer hospital days and 190 clinical events avoided over 5 years. Conclusions: Introducing cangrelor to STEMI patients with gastric absorption issues undergoing PCI in the UK is estimated to generate a small cost saving and reduced length of stay for some patients. Full article

Clopidogrel is widely used as an antiplatelet therapy for acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). Genetic factors influence variability in clopidogrel response, with non-functional CYP2C19 alleles increasing the risk of major adverse cardiovascular events (MACEs). While CYP2C19 genotype-guided therapy after PCI improves outcomes, MACEs persist at variable rates. Pharmacogenomics (PGx) has primarily focused on genes related to drug metabolism, but therapeutic failure may stem from individual disease predisposition. This study aims to identify novel genetic variants underlying adverse events after PCI despite PGx-guided therapy. A custom sequencing panel was analyzed in 244 ACS-PCI-stent patients and 99 controls without cardiovascular (CV) disease. Association analysis was performed independent of treatment and by prescribed treatment (clopidogrel or prasugrel), complemented by random forest models to predict risk during antiplatelet therapy. No polymorphism reached genomic significance, but in clopidogrel-treated patients, rs2472434 in ABCA1, related to altered lipid metabolism, was strongly associated with secondary CV events (p = 1.7 × 10⁻³). Variants in the clopidogrel pathway, including CYP2C19, ABCB1, and UGT2B7, were also identified and may influence clopidogrel response. Predictive models incorporating these variants effectively discriminated patients with and without events (p = 0.02445). Our findings support combined genotyping of CYP2C19 loss-of-function and ABCB1 C3435T variants to guide antiplatelet therapy and suggest additional targets, such as rs2472434 (ABCA1) and rs7439366 (UGT2B7), to improve risk prediction of adverse CV events. Therefore, the unexplained variability in clopidogrel response may be due to disease pathogenesis itself, highlighting the need for a paradigm shift in PGx studies. Full article

In patients on oral anticoagulation (OAC), typically for atrial fibrillation (AF), undergoing percutaneous coronary intervention (PCI), the antiplatelet drugs to be added to direct oral anticoagulant (DOAC) are aspirin and clopidogrel during the initial, short (up to one week) period of triple antithrombotic therapy (TAT), and clopidogrel alone during the subsequent 6- to 12-month period of double antithrombotic therapy (DAT). Both direct and indirect data support the recommendation to avoid the more potent P2Y12 inhibitors—ticagrelor and prasugrel—as part of TAT, owing to the increased risk of bleeding. There is less and inconclusive data available regarding the safety and efficacy of DAT when ticagrelor or prasugrel are used instead of clopidogrel. Also, there is very limited evidence for the use of aspirin instead of clopidogrel in a DAT regimen. While acknowledging the safety and effectiveness of the recommended strategies above, it would, nonetheless, be valuable to have alternative options in the choice of antiplatelet agents. In case of very high thrombotic risk, especially when stents are positioned in potentially risky sites (such as the left main or last remaining vessel) a more potent P2Y12 inhibitor than clopidogrel may be warranted. Moreover, non-responsiveness to, or pharmacological interactions of, clopidogrel may hamper its efficacy. In this review, we aim at presenting and discussing the evidence supporting the current recommendations for the use of the various antiplatelet agents in AF patients on OAC undergoing PCI, as well as at giving a glimpse at future perspectives. Full article

Background: While anticoagulant and antiplatelet therapies are commonly combined in clinical settings, this combination increases the risk of hemorrhage. However, comparative data on the bleeding risks of different drug combinations remain limited. This study assesses hemorrhage risk associated with various anticoagulant–antiplatelet combinations using data from the USFDA Adverse Event Reporting System (AERS). Methods: Hemorrhage-related reports were extracted from the AERS database (March 2004–June 2024). Anticoagulants analyzed included warfarin, rivaroxaban, dabigatran, apixaban, edoxaban, betrixaban, and acenocoumarol; antiplatelets included aspirin, clopidogrel, ticagrelor, cilostazol, prasugrel, and dipyridamole. Disproportionality analysis using frequentist and Bayesian approaches was conducted to detect hemorrhage signals. Results: Out of 160,715 hemorrhage reports, rivaroxaban, warfarin, and apixaban were the most frequently reported anticoagulants, while aspirin and clopidogrel were the top antiplatelets. Apixaban had the lowest reporting odds ratio for hemorrhage. The rivaroxaban-aspirin combination showed the highest hemorrhage risk, while combinations with cilostazol were the lowest. Apixaban, alone and in combination, was associated with reduced hemorrhage and mortality risks. Conclusions: Combining anticoagulants with antiplatelets increases hemorrhage and mortality risk. While our findings highlight potential safety signals related to hemorrhage with antithrombotic drug combinations, they remain hypothesis-generating and should not be interpreted as causal associations. Instead, they provide an initial basis for further validation in well-designed clinical cohorts where comorbidities can be adequately accounted for. Full article

Background: Dual antiplatelet therapy (DAPT) with a potent P2Y12 inhibitor is recommended for patients with acute coronary syndrome (ACS) following percutaneous coronary intervention (PCI). On-treatment platelet reactivity has been associated with ischemic endpoints and may vary between male and female patients. We, therefore, investigated sex-related differences in on-treatment platelet reactivity in ACS patients receiving ticagrelor or prasugrel. Methods: Maximal platelet aggregation by light-transmission aggregometry (LTA) and platelet surface P-selectin expression in response to arachidonic acid (AA), ADP, collagen, TRAP (a protease-activated receptor [PAR-1] agonist), and AYPGKF (a PAR-4 agonist) were assessed in 80 prasugrel- and 77 ticagrelor-treated patients 3 days after PCI. Results: In the overall study population (n = 157), women were older and had lower serum creatinine, hemoglobin, and hematocrit levels than men (all p < 0.05). Women exhibited higher ADP-inducible platelet aggregation in response to both 10 μM and 5 μM of ADP (both p < 0.05), while no sex-related differences were observed for AA-, TRAP-, collagen-, or AYPGKF-inducible platelet aggregation and agonist-inducible platelet surface P-selectin expression. In prasugrel-treated patients, women had higher ADP-inducible platelet aggregation and P-selectin expression compared with men (both p < 0.05), whereas no sex-related differences were found in ticagrelor-treated patients. In the multivariate linear regression analyses, female sex remained an independent predictor of higher platelet aggregation in response to 5 μM of ADP in prasugrel-treated patients (p < 0.05). High on-treatment residual platelet reactivity (HRPR) in response to AA was detected in four patients, and HRPR ADP was seen in seven patients, with no significant differences between female and male ACS patients (both p > 0.05). Low on-treatment residual platelet reactivity (LRPR) in response to AA was identified in 153 patients and LRPR ADP was present in 80 patients, with a higher prevalence of LRPR ADP in men (p = 0.01). Conclusions: Female ACS patients on prasugrel exhibited higher ADP-inducible platelet aggregation than male patients, while no sex-related differences were observed in patients on ticagrelor. Full article

Background: Reduced-dose prasugrel is widely used in East Asia for acute coronary syndrome (ACS), but real-world data in diverse Asian populations are limited. This study evaluated its effectiveness and safety in Taiwanese patients. Methods: The PROMISE-TW Registry was a multicenter, retrospective study including 1167 patients with ACS or chronic coronary syndrome (CCS) treated with reduced-dose prasugrel (20 mg loading, 3.75 mg maintenance) across 13 hospitals in Taiwan from 2018 to 2022. The primary endpoint was 1-year major adverse cardiovascular events (MACEs: cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke). Secondary outcomes included composite ischemic events and major bleeding (BARC 3–5). Results: Among enrolled patients (mean age 63.9 years; 81.2% male; 83% ACS), percutaneous coronary intervention was performed in 90.8%. At one year, MACEs occurred in 1.9%, composite ischemic events in 8.2%, and major bleeding in 0.8%. Subgroup analysis identified prior stroke, diabetes, and chronic total occlusion intervention as predictors of bleeding. Male sex, chronic kidney disease, and left circumflex artery intervention predicted higher ischemic risk. Conclusions:Reduced-dose prasugrel provided effective ischemic protection and low bleeding rates in Taiwanese patients, especially those with ACS. These findings support the clinical utility of dose-adjusted prasugrel in East Asian populations and highlight the importance of individualized risk assessment. Full article

Cardiovascular disease is the primary cause of mortality and morbidity in patients with chronic kidney disease (CKD), particularly those with end-stage renal disease (ESRD) undergoing hemodialysis. This paper examines the challenges of managing acute coronary syndrome (ACS) in ESRD patients, focusing on the delicate balance between thrombotic and bleeding risks. The review explores the mechanisms underlying the increased thrombotic risk in ESRD, including elevated platelet aggregation, endothelial dysfunction, and alterations in coagulation factors. Paradoxically, ESRD patients also exhibit higher bleeding tendencies due to platelet dysfunction and other uremia-related factors. The efficacy and safety of various antiplatelet therapies, including aspirin and P2Y12 inhibitors, are evaluated in this population. While potent P2Y12 inhibitors such as ticagrelor and prasugrel have demonstrated potential in reducing ischemic events, they are associated with an increased bleeding risk. The optimal duration of anti-platelet therapy (DAPT) in ESRD patients remains controversial, with studies suggesting potential benefits of prolonged DAPT but also increased bleeding risk. This review underscores the necessity for further research and patient inclusion in clinical trials to establish evidence-based guidelines for tailoring antithrombotic therapy in this high-risk population. Full article

Introduction: A direct head-to-head comparison between potent P2Y12 inhibitors: prasugrel versus ticagrelor is still lacking. Purpose: In this single-center study, we sought to address the efficacy and safety of these two third-generation antiplatelet drugs, after about a decade of practical use. Methods: A retrospective observational study included all patients who were admitted with acute coronary syndrome between January 2010 and December 2019 and were discharged with aspirin and either prasugrel or ticagrelor after percutaneous coronary intervention. Patients were divided into two groups based on the dual antiplatelet drugs prescribed. Primary endpoint: A composite endpoint of cardiovascular death, recurrent coronary syndrome, or ischemic stroke at one year. Secondary endpoint: Significant bleeding according to the BARC classification (types 3, 4, or 5). Results: During this period, 746 patients met the inclusion criteria. The primary endpoint was reached in 70 patients (9.4%): 24 patients (8.0%) in the group treated with ticagrelor and 46 patients (10.3%) in the group treated with prasugrel (p-value = 0.303). In terms of safety events, significant bleeding was not statistically different between the ticagrelor and prasugrel groups: 13 (2.9%) vs. 9 (3%), respectively (p-value = 0.9). More patients discontinued their treatment before the end of the year among those treated with ticagrelor compared to those treated with prasugrel (16.7% vs. 9.6%, p-value = 0.003). Conclusions: There was no significant difference in the occurrence of recurrent cardiac events, stroke, or cardiovascular death, nor significant bleeding among ACS patients treated either with prasugrel or ticagrelor. Full article

Bleeding complications are a significant concern in the management of acute coronary syndromes (ACS). The evidence from clinical trials demonstrates the need for balancing efficacy in reducing ischemic events with safety concerns, as bleeding events adversely affect prognosis and mortality. Pharmacological agents like aspirin, P2Y12 inhibitors (e.g., prasugrel, ticagrelor), glycoprotein IIb/IIIa inhibitors, and heparins are fundamental to ACS treatment but carry varying bleeding risks depending on individual patient profile. Recent advancements in risk stratification tools have enabled tailored approaches to dual antiplatelet therapy (DAPT), optimizing its duration based on bleeding and thrombotic risks. Further Emerging therapies, including shortened DAPT protocols and P2Y12 inhibitor monotherapy, have shown promise in minimizing bleeding while maintaining clinical efficacy. The findings underscore the importance of personalized antithrombotic regimens in ACS management, emphasizing precise risk assessment to enhance outcomes and mitigate adverse events. This review examines the mechanisms, risk factors, and strategies to mitigate bleeding associated with anticoagulant and antiplatelet therapies in ACS. Full article

Background/Objectives: The efficacy and safety of reduced-dose prasugrel (loading dose/maintenance dose: 20/3.75 mg) in preventing major adverse cardiovascular events (MACEs) among patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) have been well-estab-lished. However, long-term real-world data for this population remains limited in Taiwan. Methods: This study enrolled 226 Taiwanese ACS patients (with 448 lesions) who received reduced-dose pra-sugrel after PCI and completed one year of follow-up. Results: The primary efficacy outcome was the in-cidence of MACEs. After one year, the MACE rate was 7.1% (16/226). A comparative analysis of MACEs was conducted across subgroups stratified by age (<75 vs. ≥75 years), body mass index (<25 vs. ≥25 kg/m²), body weight (<60 vs. ≥60 kg), and estimated glomerular filtration rate (<60 vs. ≥60 mL/min/1.73 m²). Patients with impaired renal function had a 4.03-fold higher risk (95% con-fidence interval = 1.37–11.90, p = 0.01) of MACEs than those with optimal renal function. The primary safety endpoint was major bleeding events (Bleeding Academic Research Consortium types 3 or 5), which occurred in 0.8% (2/226) of patients, all gastrointestinal. The secondary end-point was net adverse clinical events (NACEs), a composite of MACEs and major bleeding, with an observed rate of 8.0% (18/226). Conclusions: Reduced-dose prasugrel demonstrated both safety and efficacy in Taiwanese ACS patients undergoing PCI. Full article

Dual antiplatelet therapy (DAPT), which is essential in AMI management, combines aspirin with a P2Y12 receptor antagonist. This study compared the effectiveness of potent P2Y12 inhibitors versus clopidogrel in AMI patients treated with percutaneous coronary intervention (PCI). Methods: 65,986 AMI patients included in a nationwide prospective registry who underwent PCI and received DAPT were studied. In total, 9,014 patients received potent P2Y12 inhibitors, and 56,074 received clopidogrel. This study focused on mortality, recurrent myocardial infarction, stroke, repeat revascularization, and major adverse cardiovascular events (MACE) over seven years. The analysis utilized unadjusted models and inverse probability of treatment weighting (IPTW) to compare prognosis, and decision curve analyses were constructed to aid clinical decision making. Results: Potent P2Y12 inhibitors significantly reduced mortality risk (unadjusted hazard ratio (HR): 0.58; IPTW HR: 0.68) and MACE (unadjusted HR: 0.66; IPTW HR: 0.78). Diabetic patients showed greater benefits (HR:0.45). In patients at high bleeding risk, the mortality rate was 13% (HR: 0.87, p = 0.08). For patients aged 75–79, the HR for mortality was 0.82, whereas for those aged >80 years, it was 0.79, indicating significant mortality risk reduction. Similar trends were observed for MACE. Conclusion: This study demonstrated that potent P2Y12 inhibitors are more effective than clopidogrel in reducing mortality and MACE in patients with AMI and underscored their potential role in improving outcomes across diverse patient subgroups. The trend was consistent even during the COVID-19 pandemic. These findings highlight the need for personalized DAPT strategies, particularly for high-bleeding-risk patients, and challenge current guidelines favoring clopidogrel use in older patients. Full article

The lipophilicity of a substance is an important physicochemical parameter for the pharmacological activity of a drug. In the current study, high-performance thin-layer chromatography was applied to determine the LogP values of the following anticoagulant drugs: warfarin, acenocoumarol, clopidogrel, and prasugrel. The mobile phase was a mixture of acetonitrile and water in mixed proportions. The content of acetonitrile varied from 50% to 80% in 5% increments. The partition coefficients were calculated with the regression curve R_m0 = f(LogP) based on the compounds with known lipophilicity. The highest LogP was observed for warfarin and the lowest for prasugrel. Full article

Introduction: Patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) require dual antiplatelet therapy (DAPT). However, the response to treatment can vary considerably. Certain platelet microRNAs (miRs) are suspected to predict DAPT response and influence platelet function. This study aimed to analyze selected miRs’ expressions and compare them among patients treated with different P2Y₁₂ inhibitors while assessing their association with platelet activity and turnover parameters. Materials and methods: We recruited 79 ACS patients post-PCI treated with clopidogrel, ticagrelor, or prasugrel, along with 18 healthy volunteers. Expression levels of miR-126-3p, miR223-3p, miR-21-5p, miR-197-3p, and miR-24-3p, as well as immature platelet fraction (IPF) and ADP-induced platelet reactivity, were measured and compared between groups. Results: Analyses revealed significantly lower expressions of miR-126-3p, miR-223-3p, miR-21-5p, and miR-197-3p in patients treated with ticagrelor, compared to clopidogrel (fold changes from −1.43 to −1.27, p-values from 0.028 to 0.048). Positive correlations were observed between platelet function and the expressions of miR-223-3p (r = 0.400, p = 0.019) and miR-21-5p (r = 0.423, p = 0.013) in patients treated with potent drugs. Additionally, miR-24-3p (r = 0.411, p = 0.012) and miR-197-3p (r = 0.333, p = 0.044) showed correlations with IPF. Conclusions: The identified platelet miRs hold potential as biomarkers for antiplatelet therapy. (ClinicalTrials.gov number, NCT06177587). Full article