Aspirin Desensitization and Percutaneous Coronary Intervention in a Patient with Aspirin Hypersensitivity and Acute Coronary Syndrome: A Case Report.

Hypersensitivity to aspirin is rare disorder occurring in 1.88% of the patients. Aspirin-hypersensitive patients requiring single antiplatelet agent may be treated with clopidogrel, an alternative antiplatelet agent. However, aspirin desensitization is more cost-effective than the usage of clopidogrel in these patients. Furthermore, aspirin desensitization is of greater value in patients requiring dual antiplatelet therapy, for example following procedures like percutaneous transluminal coronary angioplasty (PTCA) instead of using non-aspirin-based combinations. Herein, we report a 74-year-old hypertensive male presented with features of acute coronary syndrome and planned for percutaneous transluminal coronary angioplasty of RCA followed by dual antiplatelet therapy. Since he had aspirin allergy, desensitization was done using rapid desensitization protocol for which he responded well. This case highlights the importance of aspirin-desensitization in patients with aspirin allergy instead of choosing non-aspirin based antiplatelet agents.

Antiplatelet Strategy for Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Optimal duration and choice of antiplatelet therapy in patients with acute coronary syndrome undergoing percutaneous coronary intervention remain controversial. METHODS AND RESULTS: Digital databases (PubMed, Cochrane, and Embase) were queried to select all randomized controlled trials on a post-percutaneous coronary intervention population with acute coronary syndrome. Dual-antiplatelet therapy (DAPT) with aspirin and clopidogrel for 12 months was compared with 4 major strategies: high-potency, high- to low-potency, low-dose, and short-duration DAPT. A network meta-analysis was performed to compare the safety and efficacy of different antiplatelet strategies. This study was the second updated manuscript under the International Prospective Register of Systematic Review registration (CRD42021286552). Thirty-two randomized controlled trials comprising 103 459 (51 750 experimental, 51 709 control) patients were included. Compared with DAPT with aspirin and clopidogrel for 12 months, high- to low-potency DAPT (risk ratio [RR], 0.69 [95% CI, 0.52-0.92]) and aspirin+prasugrel containing DAPT for 12 months (RR, 0.84 [95% CI, 0.72-0.98]) had a significantly lower, whereas DAPT for 1 month followed by clopidogrel only (RR, 1.59 [95% CI, 1.06-2.39]) had a higher, incidence of major adverse cardiovascular events at 1 year (median follow-up). Prasugrel (RR, 1.35 [95% CI, 1.09-1.66]) and ticagrelor (RR, 1.38 [95% CI, 1.17-1.62]) containing DAPT for 12 months had significantly higher rates, whereas high- to low-potency DAPT (RR, 0.85 [95% CI, 0.63-1.15]) had no significant risk of major bleeding. CONCLUSIONS: Aspirin and ticagrelor for 3 months, followed by aspirin and clopidogrel for the remaining duration, can be considered the optimal strategy for treating post-percutaneous coronary intervention patients with acute coronary syndrome because of a significantly reduced risk of major adverse cardiovascular events without increasing the risk of bleeding.

A retrospective study of the safety and efficacy of clopidogrel versus aspirin monotherapy one year after coronary stent implantation.

BACKGROUND: The ideal single antiplatelet therapy for long-term maintenance after coronary stenting remains uncertain. In a head-to-head comparison, we aimed to evaluate the efficacy and safety profile of aspirin and clopidogrel as monotherapies in this patient cohort. METHOD: We reviewed 1044 patients who underwent percutaneous coronary intervention (PCI) with drug-eluting stents (DES) at the Department of Cardiovascular Medicine, Jinshan Hospital of Fudan University, between January 2019 and December 2021 and completed a 12-month Dual Antiplatelet Therapy (DAPT) treatment. They were divided into two groups: 582 were assigned to the aspirin group (100 mg/day) and 422 to the clopidogrel group (75 mg/day). The primary endpoint was the composite cardiac death, ischemic stroke, myocardial infarction, and Bleeding Academic Research Consortium (BARC) bleeding type 3 or greater. Secondary endpoint events included all-cause death, ischemic stroke, myocardial infarction, bleeding (defined as a BARC type ≥ 2 bleeding), and gastrointestinal complications. RESULTS: After a mean observation period of 25 ± 8.4 months, the primary endpoint event occurred in 29 (6.8%) patients in the clopidogrel group and 30 (5.1%) in the aspirin group, with no difference between the two groups (P = 0.253). In BARC type 2 or greater bleeding events, there were 9 (1.5%) in the aspirin group compared to 7 (1.7%) in the clopidogrel group, with no difference between the two groups (P = 0.160). CONCLUSION: After 12-month DAPT in Chinese patients undergoing DES implantation, aspirin monotherapy versus clopidogrel monotherapy showed no significant difference between the two drugs in terms of safety and efficacy in terms of hemorrhage, myocardial infarction, ischemic stroke, cardiac death, and bleeding with BARC type 2 or greater.

Association of Clopidogrel with Interstitial Lung Disease: Gaining Insight Through the Japanese Pharmacovigilance Database.

Background: The P2Y12 receptor inhibitors clopidogrel and prasugrel are widely used. Clopidogrel and prasugrel have different metabolic pathways, but whether their adverse event (AE) profiles differ significantly is unclear. Objective: This study aimed to compare the possible AEs induced by clopidogrel and prasugrel and to assess the rank-order of their AEs submitted to a spontaneous reporting database. Materials and Methods: Data were extracted from the Japanese Adverse Drug Event Report database (JADER). Reports of AEs associated with clopidogrel and prasugrel were analyzed to calculate the reporting odds ratios (RORs) and 95% confidence intervals (CIs). Results: Based on 5869 reports for clopidogrel (69.6%, men) and 513 reports for prasugrel (74.1%, men), 703 and 135 different AEs were identified, respectively. Bleeding complications including hemorrhage were commonly reported for both clopidogrel and prasugrel. As for AEs related to clopidogrel, unexpected AEs such as interstitial lung disease (227 reports; ROR, 1.77; 95% CI, 1.49-2.10), abnormal hepatic function (137 reports; ROR, 1.27; 95% CI, 1.07-1.51), and hepatocellular injury (96 reports; ROR, 120.0; 95% CI, 94.9-151.8) ranked at relatively high positions based on the number of occurrences, unlike prasugrel. Conclusion: This analysis of the national pharmacovigilance database highlights distinct AE profiles for clopidogrel and prasugrel. Unexpected AEs associated with clopidogrel were identified, providing valuable insights for clinical monitoring and patient safety.

The prognostic difference study on the individualized clopidogrel administration in Hmong and Dong patients based on the CYP2C19 gene polymorphism after percutaneous coronary intervention.

This study explored the distribution characteristics of CYP2C19 gene polymorphism among Hmong and Dong patients in the Qiandongnan region of Guizhou province after percutaneous coronary intervention (PCI). The aim was to assess the clinical impact of individualized clopidogrel administration based on CYP2C19 genotypes. A total of 208 patients were classified into ultra-fast, fast, intermediate, and slow metabolic groups. They were randomly assigned to clopidogrel individualized administration (IA) or conventional treatment (CA) groups. Patients were followed for 6 months to evaluate major adverse cardiovascular events (MACE) and adverse reactions. The CYP2C19 genotype distribution was in Hardy-Weinberg equilibrium, showing consistency in the population. While no significant ethnic differences were found in genotype and metabolic distribution, allele distribution varied, with Hmong patients exhibiting a higher proportion of CYP2C19*1 alleles than Dong patients. Following individualized administration, the IA group demonstrated lower incidences of non-fatal myocardial infarction and emergency revascularization compared to the CA group. Bleeding events were higher in the IA group, but the total MACE incidence was lower. No statistical difference in MACE and adverse drug reactions (ADR) was observed in the CA group across metabolic types, but MACE incidence was higher in intermediate and slow metabolic groups. In the IA group, no significant difference in MACE was noted among metabolic types, but ADR incidence varied significantly, particularly in dyspnea. The study highlighted significant CYP2C19 allele distribution differences between Hmong and Dong patients post-PCI in Qiandongnan. Patients with slow metabolic profiles demonstrated higher MACE incidence with conventional clopidogrel dosage, whereas CYP2C19-guided therapy reduced MACE without increasing bleeding risk. These findings supported clinical individualized clopidogrel administration in post-PCI patients in the Qiandongnan region, contributing to rational clopidogrel use.

Dual Antiplatelet Therapy and Outcomes in Acute Mild to Moderate Stroke With Versus Without Large-Artery Atherosclerosis Post Hoc Analysis of ATAMIS.

BACKGROUND: We conducted a post hoc analysis of the ATAMIS (Antiplatelet Therapy in Acute Mild to Moderate Ischemic Stroke) trial to investigate whether the priority of clopidogrel plus aspirin to aspirin alone was consistent between patients with and without stroke pathogenesis of large-artery atherosclerosis (LAA). METHODS AND RESULTS: Patients with stroke classification randomized to a clopidogrel-plus-aspirin group and aspirin-alone group in a modified intention-to-treat analysis set of ATAMIS were classified into LAA and non-LAA subtypes. The primary outcome was early neurologic deterioration at 7 days, defined as a >2-point increase in National Institutes of Health Stroke Scale score compared with baseline, and safety outcomes were bleeding events and intracranial hemorrhage. We compared treatment effects in each stroke subtype and investigated the interaction. Among 2910 patients, 225 were assigned into the LAA subtype (119 in the clopidogrel-plus-aspirin group and 106 in the aspirin-alone group) and 2685 into the non-LAA subtype (1380 in the clopidogrel-plus-aspirin group and 1305 in the aspirin-alone group). Median age was 66 years, and 35% were women. A lower proportion of early neurologic deterioration was found to be associated with dual antiplatelet therapy in the LAA subtype (adjusted risk difference, -10.4% [95% CI, -16.2% to -4.7%]; P=0.001) but not in the non-LAA subtype (adjusted risk difference, -1.4% [95% CI, -2.6% to 0.1%]; P=0.06). No significant interaction was found (P=0.11). CONCLUSIONS: Compared with the non-LAA subtype, patients with stroke of the LAA subtype may get more benefit from dual antiplatelet therapy with clopidogrel plus aspirin with respect to early neurologic deterioration at 7 days. REGISTRATION: URL: clinicaltrials.gov; UnIque identifier: NCT02869009.

Clopidogrel Versus Aspirin as Chronic Maintenance Antiplatelet Monotherapy in Patients After Percutaneous Coronary Intervention With Chronic Kidney Disease: A Post Hoc Analysis of the HOST-EXAM Trial.

BACKGROUND: Clopidogrel monotherapy improved clinical outcomes compared with aspirin monotherapy during a chronic maintenance period in patients who underwent coronary stenting in the HOST-EXAM (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-Extended Antiplatelet Monotherapy) trial. However, it is uncertain whether the beneficial effect of clopidogrel over aspirin is different according to the renal function. METHODS AND RESULTS: We conducted a post hoc analysis of the HOST-EXAM trial. Chronic kidney disease (CKD) was defined as baseline estimated glomerular filtration rate <60 mL/min per 1.73 m2. The primary end point was a composite of all-cause death, nonfatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and Bleeding Academic Research Consortium bleeding type ≥3, during the 2-year follow up. Among the 5438 patients enrolled in the HOST-EXAM trial, 4844 patients (mean age, 63.3±10.6 years; 74.9% men) with a baseline creatinine value were analyzed in this study. A total of 508 (10.5%) patients had CKD, who were at higher risk of the primary end point compared with those without CKD (hazard ratio [HR], 2.01 [95% CI, 1.51-2.67]). Clopidogrel monotherapy was associated with a lower rate of the primary end point in both patients with CKD (HR, 0.74 [95% CI, 0.44-1.25]) and patients without CKD (HR, 0.71 [95% CI, 0.56-0.91]). No significant interaction was observed between the treatment effect and CKD status (P for interaction=0.889). CONCLUSIONS: During the chronic maintenance period after coronary stenting, the risk of thrombotic and bleeding events was significantly higher in patients with CKD compared with those without CKD. There was no statistical difference in the treatment effect of clopidogrel monotherapy in those with versus without CKD.

Impact of CYP2C19 Genotype Status on Clinical Outcomes in Patients with Symptomatic Coronary Artery Disease, Stroke, and Peripheral Arterial Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Clopidogrel is widely used for the secondary prevention of atherothrombotic events in patients with coronary artery disease (CAD), ischemic stroke, and peripheral arterial disease (PAD). CYP2C19 plays a pivotal role in the conversion of clopidogrel to its active metabolite. Clopidogrel-treated carriers of a CYP2C19 loss-of-function allele (LOF) may have a higher risk of new atherothrombotic events. Previous studies on genotype-guided treatment were mainly performed in CAD and showed mixed results. PURPOSE: To simultaneously investigate the impact of CYP2C19 genotype status on the rate of atherothrombotic events in the most common types of atherosclerotic disease (CAD, stroke, PAD). METHODS: A comprehensive search in Pubmed, EMBASE, and MEDLINE from their inception to July 23rd 2023 was performed. Randomized controlled trials (RCTs) comparing genotype-guided and standard antithrombotic treatment, and cohort studies and post hoc analyses of RCTs concerning the association between CYP2C19 genotype status and clinical outcomes in clopidogrel-treated patients were included. The primary efficacy endpoint was major adverse cardiovascular events (MACE) and the safety end point major bleeding. Secondary endpoints were myocardial infarction, stent thrombosis, and ischemic stroke. RESULTS: Forty-four studies were identified: 11 studies on CAD, 29 studies on stroke, and 4 studies on PAD. In CAD, genotype-guided therapy significantly reduced the risk of MACE [risk ratio (RR) 0.60, 95% confidence interval (CI) 0.43-0.83], myocardial infarction (RR 0.53, 95% CI 0.42-0.68), and stent thrombosis (RR 0.64, 95% CI 0.43-0.94), compared with standard antithrombotic treatment. The rate of major bleeding did not differ significantly (RR 0.93, 95% CI 0.70-1.23). Most RCTs were performed in patients after percutaneous coronary intervention (9/11). In stroke, LOF carriers had a significantly higher risk of MACE (RR 1.61, 95% CI 1.25-2.08) and recurrent ischemic stroke (RR 1.89, 95% CI 1.48-2.40) compared with non-carriers. No significant differences were found in major bleeding (RR 0.90, 95% CI 0.43-1.89). In the 6955 patients with symptomatic PAD treated with clopidogrel in the EUCLID trial, no differences in MACE or major bleeding were found between LOF carriers and non-carriers. In three smaller studies on patients with PAD treated with clopidogrel after endovascular therapy, CYP2C19 genotype status was significantly associated with atherothrombotic events. CONCLUSIONS: Genotype-guided treatment significantly decreased the rate of atherothrombotic events in patients with CAD, especially after PCI. In patients with history of stroke, LOF carriers treated with clopidogrel had a higher risk of MACE and recurrent stroke. The available evidence in PAD with regard to major adverse limb events is too limited to draw meaningful conclusions. REGISTRATION: PROSPERO identifier no. CRD42020220284.

Comparison of uric acid elevation between aspirin-ticagrelor and aspirin-clopidogrel during dual antiplatelet therapy.

OBJECTIVE: This study investigated whether serum uric acid levels are more elevated in the aspirin-ticagrelor group than in the aspirin-clopidogrel group. Materials and Materials and methods: We conducted a retrospective cohort study with patients between 2013 and 2020. Baseline and maximum serum uric acid levels within a 6-month follow-up period were analyzed to determine the increase in both groups. RESULTS: A total of 41,877 patients were enrolled. A statistically significant elevation of serum uric acid levels was found in the aspirin-ticagrelor group compared to the aspirin-clopidogrel group (odds ratio (OR; 95% confidence interval (CI)) = 1.36 (1.15 - 1.60), p < 0.001). Kidney dysfunction and diuretic use were also identified as risk factors for uric acid elevation. CONCLUSION: Monitoring serum uric acid levels is recommended during aspirin-ticagrelor therapy, especially in patients with kidney dysfunction or those using diuretics.

Outcomes of Ticagrelor Versus High-dose Clopidogrel in CYP2C19 Intermediate Metabolizer Undergoing Percutaneous Coronary Intervention for Acute Coronary Syndromes.

ABSTRACT: Guidelines on antiplatelet recommendation for CYP2C19 intermediate metabolizer (IM) have not come to an agreement. This study aimed to evaluate the clinical benefit of ticagrelor when compared with high-dose clopidogrel in CYP2C19 IM after percutaneous coronary intervention for acute coronary syndromes. Patients were enrolled according to CYP2C19 genotype and individual antiplatelet therapy. Patient characteristics and clinical outcomes were collected through electronic medical record system. The primary outcome was major adverse cardiac and cerebrovascular event (MACCE), namely a composite of death from cardiovascular causes, myocardial infarction, stroke, and stent thrombosis within 12 months. The secondary outcome was Bleeding Academic Research Consortium scale bleeding events within 12 months. The Cox proportional hazards regression model was performed, with inverse probability treatment weighting (IPTW) adjusting for potential confounders. A total of 532 CYP2C19 IM were enrolled in this retrospective single-center study. No statistically significant difference in incidence rate of MACCE was found between patients receiving ticagrelor versus clopidogrel (7.01 vs. 9.52 per 100 patient-years; IPTW-adjusted hazard ratio 0.71; 95% confidence interval: 0.32-1.58; adjusted log-rank P = 0.396), but the incidence rate of Bleeding Academic Research Consortium type 2, 3, or 5 bleeding events was statistically higher in the loss of function-ticagrelor group than in the loss of function-clopidogrel group (13.53 vs. 6.16 per 100 patient-years; IPTW-adjusted hazard ratio: 2.29; 95% confidence interval: 1.10-4.78; adjusted log-rank P = 0.027). Ticagrelor treatment in CYP2C19 IM resulted in a statistically higher risk of bleeding compared with high-dose clopidogrel, whereas a clear association between treatments and MACCE warrants further investigations.

Comparison of clinical outcomes between ticagrelor and clopidogrel in patients with acute coronary syndrome and left ventricle dysfunction undergoing percutaneous coronary intervention: An observational study.

Patients with acute coronary syndrome (ACS) and left ventricular (LV) dysfunction undergoing percutaneous coronary intervention (PCI) need adequate antithrombotic protection. We aim to compare the clinical outcomes between ticagrelor and clopidogrel in these patients. In total, 336 patients with ACS and LV dysfunction who undergoing PCI were included in this retrospective observational study. Of these, 137 received clopidogrel and 199 received ticagrelor. There was a 6-month follow-up period during which clinical outcomes were monitored. The incidence of the composite endpoint (23.1% vs 13.9%, P = .041) and bleeding events (6.5% vs 1.5%, P = .027) in the ticagrelor group were significantly higher compared to the clopidogrel group. Multivariate logistic regression analysis revealed that age (P = .006), hypertension (P = .007), liver insufficiency (P = .022), previous MI (P = .014) and ticagrelor (P = .044) were independent risk factors that affect the efficacy outcome. Age (P = .027) and ticagrelor (P = .016) were the independent risk factors for the safety outcome. Furthermore, in Cox survival regression analysis model, the survival rate of the efficacy endpoint in the clopidogrel group was seemingly higher than in the ticagrelor group (HR = 1.68, 95% CI: 0.97-2.90, P = .065). The survival rate of the bleeding endpoint in the clopidogrel group was higher than in the ticagrelor group (HR = 2.00, 95% CI: 1.17-3.40, P = .011). Compared to clopidogrel, ticagrelor showed increased risk of efficacy outcome and major bleeding events during 6-month follow-up in patients with ACS and LV dysfunction undergoing PCI.

Time to treatment and disability attributed to index stroke in the POINT trial.

BACKGROUND: In the Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial, dual antiplatelet therapy (DAPT) was associated with reduced disability attributable to the index stroke compared to antiplatelet monotherapy. However, it is unknown whether earlier treatment with DAPT versus aspirin is associated with greater benefit. METHODS: We analyzed patients enrolled in POINT with minor ischemic stroke who had available data recording the treatment initiation time and modified Rankin Scale (mRS) at 90 days. Patients were randomized to DAPT (aspirin plus clopidogrel) vs. aspirin alone within 12 h of symptom onset. We estimated the effect of DAPT on disability (defined as mRS>1) ascribed to the index event and major hemorrhage at 90 days, stratified by tertiles of time from symptom onset-to-treatment-initiation. RESULTS: A total of 2559 patients were included; median onset-to-treatment-initiation time was 8.3 h (IQR:5.8-11.0). Comparing DAPT to aspirin, the rate of disability attributed to the index event at 90-day follow-up was 5.1 % vs. 8.6 % (OR 0.57; 95 % CI:0.33-0.99) in patients treated <6.7 h, 7.5 % vs. 9.9 % (OR 0.74; 95 % CI:0.45-1.19) in those treated 6.7-10.0 h, and 8.6 % vs. 10.6 % (OR 0.80; 95 % CI:0.50-1.26) in those treated >10.0 h after symptom onset (p for interaction=0.65). There was no difference in major hemorrhage across time strata. CONCLUSIONS: While not statistically significant, these results suggest the possibility of greater efficacy at reducing disability ascribed to minor stroke with earlier treatment with DAPT compared to aspirin. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Identifier: NCT00991029.

Clopidogrel Versus Aspirin as Monotherapy Following Dual Antiplatelet Therapy in Patients With Acute Coronary Syndrome Receiving a Drug-Eluting Stent: A Systematic Literature Review and Meta-Analysis.

OBJECTIVE: This study aimed to evaluate the comparative effectiveness and safety of clopidogrel versus aspirin as monotherapy following adequate dual antiplatelet therapy (DAPT) in patients with acute coronary syndrome (ACS). METHODS: MEDLINE, Embase, and CENTRAL were searched from database inception to September 1, 2023. Randomized controlled trials (RCTs) and observational studies evaluating the effectiveness or safety of clopidogrel versus aspirin as monotherapy following DAPT in patients with ACS who received a drug-eluting stent were included. Random-effects meta-analyses were conducted to compare risks of major adverse cardiovascular events (MACE) and clinically relevant bleeding. RESULTS: Of 6242 abstracts identified, three unique studies were included: one RCT and two retrospective cohort studies. Studies included a total of 7081 post-percutaneous coronary intervention ACS patients, 4260 of whom received aspirin monotherapy and 2821 received clopidogrel monotherapy. Studies included variable proportions of patients with ST-elevation myocardial infarction (STEMI), non-STEMI, and unstable angina. From the meta-analysis, clopidogrel was associated with a 28% reduction in the risk of MACE compared with aspirin (hazard ratio [HR]: 0.72; 95% confidence interval [CI]: 0.54, 0.98), with no significant difference in clinically relevant bleeding (HR: 0.92; 95% CI: 0.68, 1.24). CONCLUSION: Despite the paucity of published evidence on the effectiveness and safety of clopidogrel versus aspirin in patients with ACS post-drug-eluting stent implantation, this meta-analysis suggests that clopidogrel versus aspirin may result in a lower risk of MACE, with a similar risk of major bleeding. The present results are hypothesis-generating and further large RCTs comparing antiplatelet monotherapy options in ACS patients are warranted.

[GDF-15 and the risk of bleeding in patients with stable CAD receiving multicomponent antithrombotic therapy: the results of the prospective REGATA register].

AIM: To evaluate the prognostic value of GDF-15 in relation the development of bleeding and events in stable CAD patients, receiving combined antithrombotic therapy. MATERIALS AND METHODS: The data was obtained from the prospective registry REGATA, 343 CAD patients (249 males), median age 68 [IQR 62; 75] years) were enrolled. Patients with sinus rhythm and concomitant PAD received acetylsalicylic acid in combination with rivaroxaban 2.5 mg bid (31.8%) or clopidogrel (24.8%). Other 43.4% with concomitant atrial fibrillation (AF) received direct oral anticoagulants in combination with antiplatelet therapy after elective percutaneous coronary interventions. Median follow-up was 12 months [IQR 9.0; 18.0]. The safety end point was major and clinically relevant bleedings (type 2-5) according to the BARC classification. Plasma samples for GDF-15 identification were taken at the inclusion and analyzed using ELISA assay. RESULTS: Frequency of BARC 2-5 bleedings was 16% (BARC 2 - 46; BARC 3 - 9; BARC 4-5 - 0), median GDF-15 level was 1185.0 pg/ml [850.0; 1680.0]. In patients with AF and concomitant MFA, the level of GDF-15 was significantly higher than in the subgroups of patients with only AF or MFA (p=0.0022). According to the quintile analysis, GDF-15 values in the top three quintiles of distribution (cut-off value >943 pg/ml) were associated with higher frequency of bleeding events: 23.2% versus 5.1%; p=0.0001. The multivariable logistic regression model demonstrated that bleeding events were independently associated with GDF-15 level>943 pg/ml (OR 2.65, 95% CI 1.11-6.30; p=0.0275), AF (OR 2.61, 95% CI 1.41-4.83; p=0.0023) and chronic kidney disease (OR 1.92, 95% CI 1.03-3.60; p=0.0401). Clinical factors determining the risk of bleeding events also determined a GDF-15 elevation. CONCLUSION: Assessment of GDF-15 level may improve bleeding risk stratification in CAD patients with concomitant AF and/or PAD receiving combined antithrombotic therapy.

Precision Antiplatelet Therapy after Percutaneous Coronary Intervention (Precision PCI) Registry - Informing optimal antiplatelet strategies.

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor (clopidogrel, prasugrel, or ticagrelor) is indicated after percutaneous coronary intervention (PCI) to reduce the risk of atherothrombotic events. Approximately 30% of the US population has a CYP2C19 no-function allele that reduces the effectiveness of clopidogrel, but not prasugrel or ticagrelor, after PCI. We have shown improved outcomes with the integration of CYP2C19 genotyping into clinical care to guide the selection of prasugrel or ticagrelor in CYP2C19 no-function allele carriers. However, the influence of patient-specific demographic, clinical, and other genetic factors on outcomes with genotype-guided DAPT has not been defined. In addition, the impact of genotype-guided de-escalation from prasugrel or ticagrelor to clopidogrel in patients without a CYP2C19 no-function allele has not been investigated in a diverse, real-world clinical setting. The Precision Antiplatelet Therapy after Percutaneous Coronary Intervention (Precision PCI) Registry is a multicenter US registry of patients who underwent PCI and clinical CYP2C19 testing. The registry is enrolling a diverse population, assessing atherothrombotic and bleeding events over 12 months, collecting DNA samples, and conducting platelet function testing in a subset of patients. The registry aims to define the influence of African ancestry and other patient-specific factors on clinical outcomes with CYP2C19-guided DAPT, evaluate the safety and effectiveness of CYP2C19-guided DAPT de-escalation following PCI in a real-world setting, and identify additional genetic influences of clopidogrel response after PCI, with the ultimate goal of establishing optimal strategies for individualized antiplatelet therapy that improves outcomes in a diverse, real-world population.

Effect of different anticoagulants and antiplatelets on intraoral bleeding time during professional oral hygiene session.

OBJECTIVE: Patients with thromboembolic problems, prosthetic valves, or coagulation issues are commonly prescribed anticoagulants and antiplatelets. Anticoagulant and antiplatelet medication might constitute a challenge for dentists and dental hygienists since possible prolonged bleeding might interfere with dental procedures. The aim of the present study was to examine the bleeding durations associated with various anticoagulants and antiplatelets during professional dental hygiene sessions, utilizing a modified Ivy test adapted for the oral context. MATERIALS AND METHODS: Ninety-three consecutive patients undergoing professional oral hygiene were recruited. Debridement during oral hygiene was performed using ultrasonic mechanical instrumentation, and bleeding sites were assessed and treated with gentle pressure using sterile gauzes. The time for bleeding cessation was recorded. Patients were categorized into six groups based on their drug intake, Control: no anticoagulants or antiplatelets DTI: direct thrombin inhibitors (dabigatran) AntiXa: directa factor Xa inhibitors (endoxaban, apixaban, rivaroxaban) VKA: vitamin K antagonists (warfarin, acenocoumarol) SAPT: single anti-platelet therapy (acetylsalicylic acid or clopidogrel) DAPT: dual anti-platelet therapy (acetylsalicylic acid and clopidogrel). Bleeding time was measured in seconds and mean values were assessed among the different groups. Differences between groups were investigated with Kruskal-Wallis test followed by Dunn's post-hoc correction for multiple comparisons or two-way ANOVA followed by Dunnett post-hoc; RESULTS: Control patients presented the lowest bleeding time 50 s, followed by AntiXa (98), SAPT (105), DTI (120), DAPT (190) and VKA (203). A statistically significant difference was present among control and DTI (p = 0.004), VKA (p < 0.001), DAPT (p < 0.001). CONCLUSIONS: Based on the present outcomes, an increased risk of prolonged bleeding emerged in patients taking VKA and DAPT. CLINICAL SIGNIFICANCE: bleeding did not interfere with the oral hygiene session The optimal period for dental treatment of these patients should be 2-3 h before the next dose, without the need to temporarily suspend the medication.

Impact of proton pump inhibitor use on clinical outcomes in East Asian patients receiving clopidogrel following drug-eluting stent implantation.

BACKGROUND: Concomitant use of clopidogrel and proton pump inhibitor (PPI) is common, but PPI may reduce the antiplatelet effects of clopidogrel in patients undergoing percutaneous coronary intervention (PCI). We evaluated the impact of PPI use on clinical outcomes in post-PCI patients, by incorporating P2Y12 reaction unit (PRU) and CYP2C19 genotyping results. METHODS: From a multicenter registry of patients who underwent PCI with drug-eluting stent implantation and received clopidogrel-based dual antiplatelet therapy (DAPT), patients who were prescribed a PPI at the time of PCI (PPI users) were compared to those who were not (non-users). The primary outcome included all-cause death, myocardial infarction, stent thrombosis, or cerebrovascular accident at 12 months. Major bleeding (Bleeding Academic Research Consortium [BARC] types 3-5) and gastrointestinal (GI) bleeding (BARC types 3-5) were important secondary outcomes. The adjusted outcomes were compared using a 1:1 propensity-score (PS) matching and competing risk analysis. RESULTS: Of 13,160 patients, 2,235 (17.0%) were prescribed PPI, with an average age of 65.4 years. PPI users had higher on-treatment PRU levels than non-users. After PS matching, the primary outcome occurred in 51 patients who were PPI users (cumulative incidence, 4.7%) and 41 patients who were non-users (cumulative incidence, 3.7%; log-rank p = 0.27). In carriers of both CYP2C19 loss-of-function alleles, PPI use was linked to an increased risk of the primary outcome (hazard ratio, 3.22; 95% confidence interval, 1.18-8.78). The incidence of major bleeding and GI bleeding (BARC types 3-5) was comparable between PPI users and non-users in the PS-matched cohort. CONCLUSIONS: In post-PCI patients receiving clopidogrel-based DAPT, PPI use was not linked to an increased risk of adverse cardiac and cerebrovascular events, but there was a small but significant increase in on-treatment PRU. Future research using a more individualized approach would further elucidate these interactions and guide evidence-based clinical practices.

Effect of Ticagrelor Versus Clopidogrel After Off-Pump Coronary Artery Bypass Grafting on Postoperative Atrial Fibrillation: A Cohort Study.

BACKGROUND: This study aimed to explore the effect of a P2Y12 inhibitor regimen on the occurrence of postoperative atrial fibrillation (POAF) after off-pump coronary artery bypass graft surgery in carriers with the cytochrome P450 family 2 subfamily C member19 loss-of-function allele. METHODS AND RESULTS: From May 2019 to November 2023, patients containing the cytochrome P450 family 2 subfamily C member19*2 or *3 allele undergoing elective first-time off-pump coronary artery bypass graft surgery including aspirin 100 mg/d and ticagrelor 180 mg/d (AT group; n=95) versus clopidogrel 75 mg/d (aspirin and clopidogrel group; n=95) were prospectively followed. The primary end point was the cumulative incidence of POAF in a week. The secondary end points were POAF burden, platelet aggregability, systemic immune-inflammation index and heart rate variability. The incidence of POAF was 21.1% in the AT group versus 41.1% in the aspirin and clopidogrel group (hazard ratio, 0.46 [95% CI, 0.27-0.76]; P=0.003). POAF burden, ADP-induced platelet aggregation and systemic immune-inflammation index was notably lower in the AT group than the aspirin and clopidogrel group. Heart rate variability data showed an increase in both high-frequency and SD of normal-to-normal RR intervals in the AT group with a decreased low-frequency/high-frequency ratio, suggesting that the sympathetic/parasympathetic activation was balanced. CONCLUSIONS: In patients carrying the cytochrome P450 family 2 subfamily C member19 loss-of-function allele, an AT regimen after off-pump coronary artery bypass grafting was associated with a lower incidence of POAF, paralleled by lower atrial fibrillation burden, ADP-induced platelet aggregation, lower systemic immune-inflammation index reaction, and a balanced automatic nerve system compared with an aspirin and clopidogrel regimen. Inhibiting the systemic immune-inflammation response and sustaining automatic nerve balance may underlie the therapeutic effect of POAF by a potent antiplatelet combination.

Efficacy and safety of aspirin plus clopidogrel versus aspirin alone in ischemic stroke or high-risk transient ischemic attack: A meta-analysis of randomized controlled trials.

Background: Antiplatelet therapy plays an important role in reducing the risk of stroke recurrence in patients with mild ischemic stroke or high-risk transient ischemic attack (TIA). However, data regarding the effectiveness and safety of using aspirin plus clopidogrel in dual antiplatelet therapy (DAPT) compared to aspirin alone in mild ischemic stroke is limited. Methods: PubMed/MEDLINE, Embase, Cochrane Library, and ClinicalTrials.gov were searched for randomized controlled trials (RCTs) that compared DAPT to aspirin alone started within 72 hours in mild ischemic stroke or high-risk TIA. We used a random effects model to pool risk ratios (RRs) along with 95% CIs for clinical outcomes. Results: Four RCTs with 16,547 patients were included in this study. DAPT significantly reduced the risk of recurrent stroke by 26% (RR: 0.74; 95% CI: 0.67-0.83; p < 0.00001), ischemic stroke by 28% (RR: 0.72; 95% CI: 0.65-0.80; p < 0.00001), and major adverse cardiovascular events (MACE) by 24% (RR: 0.76; 95% CI: 0.68-0.84; p < 0.00001) compared to aspirin monotherapy. However, DAPT was associated with a significantly increased risk of moderate or severe bleeding (RR: 1.88; 95% CI: 1.10-3.23; p = 0.02) compared to aspirin alone. No significant differences were observed for hemorrhagic stroke (RR: 1.77; 95% CI: 0.96-3.29; p = 0.07), all-cause mortality (RR: 1.25; 95% CI: 0.87-1.80; p = 0.23), cardiovascular mortality (RR: 1.38; 95% CI: 0.81-2.33; p = 0.23), and myocardial infarction (RR: 1.63; 95% CI: 0.77-3.46; p = 0.20). Conclusion: DAPT involving aspirin plus clopidogrel reduces stroke recurrence and MACE but can lead to an increased risk of moderate or severe bleeding compared to aspirin monotherapy. (PROSPERO ID: CRD42024499310).