RESUMEN
Importance: Prior trials showed that dual antiplatelet therapy could reduce the risk of early new stroke in patients with acute mild ischemic stroke or transient ischemic attack (TIA) within 24 hours of symptom onset. However, it is currently uncertain whether dual antiplatelet therapy can reduce the risk of early new stroke in patients with a more delayed initiation time window. Objective: To evaluate the efficacy and safety of clopidogrel and aspirin among patients with mild ischemic stroke or TIA when initiated within 24 hours, from more than 24 hours to 48 hours, and from more than 48 hours to 72 hours. Design, Setting, and Participants: The Intensive Statin and Antiplatelet Therapy for Acute High-Risk Intracranial or Extracranial Atherosclerosis randomized clinical trial was a double-blind, placebo-controlled, multicenter, 2-by-2 factorial randomized clinical trial conducted at 222 hospitals in China from September 17, 2018, to October 15, 2022. All patients with acute mild ischemic stroke and TIA were included in this subgroup analysis and categorized into 3 groups according to time from symptom onset to randomization (group 1: ≤24 hours; group 2: >24 to ≤48 hours; and group 3: >48 to 72 hours). Patients were followed up for 90 days. Interventions: All patients received clopidogrel combined with aspirin (clopidogrel 300 mg loading dose on day 1, followed by 75 mg daily on days 2 to 90, and aspirin 100 to 300 mg on the first day and then 100 mg daily for days 2 to 90) or aspirin alone (100 to 300 mg on day 1 and then 100 mg daily for days 2 to 90) within 72 hours after symptom onset. Main Outcomes and Measures: The primary outcome was new stroke (ischemic or hemorrhagic) within 90 days. The primary safety outcome was moderate-to-severe bleeding, according to Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries criteria. Results: This analysis included a total of 6100 patients (3050 in the clopidogrel-aspirin group and 3050 in the aspirin group). The median age was 65 years (IQR, 57-71 years), and 3915 patients (64.2%) were male. In the population with time to randomization of 24 hours or less, stroke occurred in the next 90 days in 97 of 783 patients (12.4%); among those randomized from more than 24 hours to 48 hours, in 211 of 2552 patients (8.3%) among those randomized from more than 24 hours to 48 hours, and in 193 of 2765 patients (7.0%). The clopidogrel-aspirin group had a lower risk of new stroke within 90 days compared with the aspirin alone group both in patients with time to randomization of from 48 to 72 hours (5.8% vs 8.2%; hazard ratio [HR], 0.70 [95% CI, 0.53-0.94]), of more than 24 to 48 hours (7.6% vs 8.9%; HR, 0.85 [95% CI, 0.65-1.12]), and of 24 hours or less (11.5% vs 13.4%; HR, 0.83 [95% CI, 0.55-1.25]) (P = .38 for interaction). Among those with time to randomization of more than 48 to 72 hours, moderate-to-severe bleeding occurred in 12 patients (0.9%) in the clopidogrel-aspirin group and in 6 patients (0.4%) in the aspirin-alone group (HR, 2.00 [95% CI, 0.73-5.43]), while moderate-to-severe bleeding in those with time to randomization of more than 24 hours to 48 hours occurred in 9 patients (0.7%) in the clopidogrel-aspirin group and in 4 patients (0.3%) in the aspirin-alone group (HR, 2.25 [95% CI, 0.68-7.39]) and in those with time to randomization of within 24 hours, occurred in 6 patients (1.5%) in the clopidogrel-aspirin group and in 3 patients (0.8%) in the aspirin-alone group (HR, 1.57 [95% CI, 0.36-6.83]) (P = .92 for interaction). Conclusions and Relevance: In this randomized clinical trial of antiplatelet therapy in China, patients with mild ischemic stroke or TIA had consistent benefit from dual antiplatelet therapy with clopidogrel and aspirin vs aspirin alone when initiated within 72 hours after symptom onset, with a similar increase in the risk of moderate-to-severe bleeding. Patients should receive dual antiplatelet therapy with clopidogrel and aspirin within 72 hours after symptom onset. Trial Registration: ClinicalTrials.gov Identifier: NCT03635749.
Asunto(s)
Aspirina , Clopidogrel , Accidente Cerebrovascular Isquémico , Inhibidores de Agregación Plaquetaria , Humanos , Clopidogrel/uso terapéutico , Aspirina/uso terapéutico , Aspirina/administración & dosificación , Masculino , Femenino , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/prevención & control , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/uso terapéutico , Anciano , Método Doble Ciego , Ataque Isquémico Transitorio/tratamiento farmacológico , China/epidemiología , Tiempo de Tratamiento/estadística & datos numéricos , Factores de Tiempo , Resultado del TratamientoRESUMEN
The CYP2C19 enzyme metabolizes clopidogrel, a prodrug, to its active form. Approximately 30% of individuals inherit a loss-of-function (LoF) polymorphism in the CYP2C19 gene, leading to reduced formation of the active clopidogrel metabolite. Reduced clopidogrel effectiveness has been well documented in patients with an LoF allele following an acute coronary syndrome or percutaneous coronary intervention. Prasugrel or ticagrelor is recommended in those with an LoF allele as neither is affected by CYP2C19 genotype. Although data demonstrate improved outcomes with a CYP2C19-guided approach to P2Y12 inhibitor selection, genotyping has not yet been widely adopted in clinical practice.
Asunto(s)
Citocromo P-450 CYP2C19 , Antagonistas del Receptor Purinérgico P2Y , Humanos , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Citocromo P-450 CYP2C19/genética , Síndrome Coronario Agudo/tratamiento farmacológico , Síndrome Coronario Agudo/genética , Clopidogrel/uso terapéutico , Intervención Coronaria Percutánea/métodos , Genotipo , Ticagrelor/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Clorhidrato de Prasugrel/uso terapéutico , Polimorfismo GenéticoRESUMEN
Understanding the cost-effectiveness of aspirin-clopidogrel combination therapy is crucial in determining its influence on coagulation parameters, specifically prothrombin time (PT) and activated partial thromboplastin time (APTT). The aim of this study was to assess the cost-effectiveness and clinical impact of using the aspirin-clopidogrel combination compared to aspirin alone in managing ischemic stroke. Employing an observational research design, inpatient ischemic stroke cases receiving the aspirin-clopidogrel combination were compared to those treated with aspirin alone. Focusing on the hospital's perspective on costs, the research specifically analyzed medical expenses without discounting costs or effects. The analysis involved comparing the direct medical costs and coagulation parameters between the two treatment groups. Our data revealed that the aspirin-clopidogrel combination demonstrated superior cost-effectiveness over aspirin alone, indicated by the incremental cost-effectiveness ratio (ICER) values for PT (IDR -246,930/second) and APTT (IDR -119,270/second). This indicated that the combination therapy was associated with lower costs while yielding better clinical parameter values. The ICER analysis placed the aspirin-clopidogrel combination in the southeast quadrant, marking its dominance over aspirin monotherapy by demonstrating higher effectiveness at lower costs. These results suggest that combination therapy might be a favorable alternative for managing ischemic stroke, presenting a viable option for consideration in clinical practice. The findings underscore the potential economic and clinical advantages of employing the aspirin-clopidogrel combination in routine stroke management protocols.
Asunto(s)
Aspirina , Clopidogrel , Análisis Costo-Beneficio , Quimioterapia Combinada , Accidente Cerebrovascular Isquémico , Inhibidores de Agregación Plaquetaria , Humanos , Clopidogrel/uso terapéutico , Clopidogrel/administración & dosificación , Aspirina/uso terapéutico , Aspirina/economía , Aspirina/administración & dosificación , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/economía , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/economía , Inhibidores de Agregación Plaquetaria/administración & dosificación , Femenino , Masculino , Anciano , Persona de Mediana Edad , Resultado del Tratamiento , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/economíaRESUMEN
BACKGROUND: Recently, the effect of Lipoprotein(a) [Lp(a)] on thrombogenesis has aroused great interest, while inflammation has been reported to modify the Lp(a)-associated risks through an unidentified mechanism. PURPOSE: This study aimed to evaluate the association between platelet reactivity with Lp(a) and high-sensitivity C-reactive protein (hs-CRP) levels in percutaneous intervention (PCI) patients treated with clopidogrel. METHODS: Data were collected from 10,724 consecutive PCI patients throughout the year 2013 in Fuwai Hospital. High on-treatment platelet reactivity (HTPR) and low on-treatment platelet reactivity (LTPR) were defined as thrombelastography (TEG) maximum amplitude of adenosine diphosphate-induced platelet (MAADP) > 47 mm and < 31 mm, respectively. RESULTS: 6615 patients with TEG results were finally enrolled. The mean age was 58.24 ± 10.28 years and 5131 (77.6%) were male. Multivariable logistic regression showed that taking Lp(a) < 30 mg/dL and hs-CRP < 2 mg/L as the reference, isolated Lp(a) elevation [Lp(a) ≥ 30 mg/dL and hs-CRP < 2 mg/L] was not significantly associated with HTPR (P = 0.153) or LTPR (P = 0.312). However, the joint elevation of Lp(a) and hs-CRP [Lp(a) ≥ 30 mg/dL and hs-CRP ≥ 2 mg/L] exhibited enhanced association with both HTPR (OR:1.976, 95% CI 1.677-2.329) and LTPR (OR:0.533, 95% CI 0.454-0.627). CONCLUSIONS: The isolated elevation of Lp(a) level was not an independent indicator for platelet reactivity, yet the concomitant elevation of Lp(a) and hs-CRP levels was significantly associated with increased platelet reactivity. Whether intensified antiplatelet therapy or anti-inflammatory strategies could mitigate the risks in patients presenting combined Lp(a) and hs-CRP elevation requires future investigation.
Asunto(s)
Proteína C-Reactiva , Clopidogrel , Lipoproteína(a) , Intervención Coronaria Percutánea , Humanos , Masculino , Clopidogrel/farmacología , Clopidogrel/uso terapéutico , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Lipoproteína(a)/sangre , Femenino , Persona de Mediana Edad , Intervención Coronaria Percutánea/métodos , Anciano , Ticlopidina/análogos & derivados , Ticlopidina/farmacología , Ticlopidina/uso terapéutico , Inhibidores de Agregación Plaquetaria/farmacología , Inhibidores de Agregación Plaquetaria/uso terapéutico , Plaquetas/metabolismo , Plaquetas/efectos de los fármacosRESUMEN
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.
Asunto(s)
Aspirina , Clopidogrel , Terapia Antiplaquetaria Doble , Accidente Cerebrovascular Isquémico , Inhibidores de Agregación Plaquetaria , Humanos , Femenino , Masculino , Anciano , Aspirina/administración & dosificación , Aspirina/uso terapéutico , Aspirina/efectos adversos , Clopidogrel/uso terapéutico , Clopidogrel/administración & dosificación , Clopidogrel/efectos adversos , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Terapia Antiplaquetaria Doble/métodos , Terapia Antiplaquetaria Doble/efectos adversos , Persona de Mediana Edad , Resultado del Tratamiento , Accidente Cerebrovascular Isquémico/diagnóstico , Accidente Cerebrovascular Isquémico/prevención & control , Accidente Cerebrovascular Isquémico/epidemiología , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/etiología , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/diagnóstico , Aterosclerosis/complicaciones , Índice de Severidad de la Enfermedad , Quimioterapia CombinadaRESUMEN
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.
Asunto(s)
Aspirina , Clopidogrel , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria , Insuficiencia Renal Crónica , Humanos , Clopidogrel/uso terapéutico , Clopidogrel/efectos adversos , Clopidogrel/administración & dosificación , Masculino , Femenino , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/fisiopatología , Insuficiencia Renal Crónica/terapia , Persona de Mediana Edad , Intervención Coronaria Percutánea/efectos adversos , Aspirina/administración & dosificación , Aspirina/uso terapéutico , Aspirina/efectos adversos , Anciano , Hemorragia/inducido químicamente , Resultado del Tratamiento , Tasa de Filtración Glomerular , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/terapia , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/mortalidad , Stents , Factores de TiempoRESUMEN
BACKGROUND AND OBJECTIVES: Clopidogrel-aspirin initiated within 72 hours of symptom onset is effective in patients with mild ischemic stroke or transient ischemic attack (TIA) in the Intensive Statin and Antiplatelet Therapy for Acute High-risk Intracranial or Extracranial Atherosclerosis (INSPIRES) trial. Uncertainties remain about the duration of the treatment effect. This study aimed to assess duration of benefit and risk of clopidogrel-aspirin in these patients. METHODS: The INSPIRES trial was a 2*2 factorial placebo-controlled randomized trial conducted in 222 hospitals in China. The 2 treatments did not interact and were evaluated separately. In this study, we performed secondary analyses based on antiplatelet treatment. All patients with mild stroke or TIA of presumed atherosclerotic cause within 72 hours of symptom onset enrolled in the trial were included. Patients were randomly assigned to receive clopidogrel-aspirin on days 1-21 followed by clopidogrel on days 22-90 or aspirin alone for 90 days. The primary efficacy outcome was major ischemic event which included the composite of ischemic stroke and nonhemorrhagic death. The primary safety outcome was moderate-to-severe bleeding. We estimated the risk difference between the 2 treatments for each stratified week. RESULTS: All 6,100 patients in the trial were included (3,050 in each group). The mean age was 65 years, and 3,915 patients (64.2%) were men. Compared with aspirin alone, the reduction of major ischemic events by clopidogrel-aspirin mainly occurred in the first week (absolute risk reduction [ARR] 1.42%, 95% CI 0.53%-2.32%) and remained in the second week (ARR 0.49%, 95% CI 0.09%-0.90%) and the third week (ARR 0.29%, 95% CI -0.05% to 0.62%). Numerical higher risk of moderate-to-severe bleedings in the clopidogrel-aspirin group was observed in the first 3 weeks (absolute risk increase 0.05% [95% CI -0.10% to 0.20%], 0.10% [95% CI -0.09% to 0.29%], and 0.18% [95% CI -0.03% to 0.40%] in the first, second, and third weeks, respectively). CONCLUSIONS: Among patients with mild ischemic stroke or high-risk TIA of presumed atherosclerotic cause, the net benefit of clopidogrel-aspirin initiated within 72 hours of symptom onset was pronounced in the first week and continued to a lesser degree in the following 2 weeks, outweighing the low, but ongoing hemorrhagic risk. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT03635749. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that among patients with mild ischemic stroke or high-risk TIA of presumed atherosclerotic cause, the net benefit of clopidogrel-aspirin initiated within 72 hours of symptom onset was pronounced in the first week and continued to a lesser degree in the following 2 weeks, outweighing the low but ongoing hemorrhagic risk.
Asunto(s)
Aspirina , Clopidogrel , Terapia Antiplaquetaria Doble , Ataque Isquémico Transitorio , Accidente Cerebrovascular Isquémico , Inhibidores de Agregación Plaquetaria , Humanos , Ataque Isquémico Transitorio/tratamiento farmacológico , Masculino , Femenino , Clopidogrel/uso terapéutico , Clopidogrel/administración & dosificación , Persona de Mediana Edad , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Aspirina/uso terapéutico , Aspirina/administración & dosificación , Anciano , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Terapia Antiplaquetaria Doble/métodos , Factores de Tiempo , Quimioterapia Combinada , Resultado del TratamientoRESUMEN
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%, Pâ =â .041) and bleeding events (6.5% vs 1.5%, Pâ =â .027) in the ticagrelor group were significantly higher compared to the clopidogrel group. Multivariate logistic regression analysis revealed that age (Pâ =â .006), hypertension (Pâ =â .007), liver insufficiency (Pâ =â .022), previous MI (Pâ =â .014) and ticagrelor (Pâ =â .044) were independent risk factors that affect the efficacy outcome. Age (Pâ =â .027) and ticagrelor (Pâ =â .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 (HRâ =â 1.68, 95% CI: 0.97-2.90, Pâ =â .065). The survival rate of the bleeding endpoint in the clopidogrel group was higher than in the ticagrelor group (HRâ =â 2.00, 95% CI: 1.17-3.40, Pâ =â .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.
Asunto(s)
Síndrome Coronario Agudo , Clopidogrel , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria , Ticagrelor , Disfunción Ventricular Izquierda , Humanos , Ticagrelor/uso terapéutico , Ticagrelor/efectos adversos , Clopidogrel/uso terapéutico , Clopidogrel/efectos adversos , Síndrome Coronario Agudo/tratamiento farmacológico , Síndrome Coronario Agudo/terapia , Síndrome Coronario Agudo/cirugía , Masculino , Femenino , Intervención Coronaria Percutánea/métodos , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/efectos adversos , Resultado del Tratamiento , Factores de Riesgo , Hemorragia/inducido químicamente , Hemorragia/epidemiologíaRESUMEN
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.
Asunto(s)
Clopidogrel , Citocromo P-450 CYP2C19 , Intervención Coronaria Percutánea , Polimorfismo Genético , Humanos , Citocromo P-450 CYP2C19/genética , Clopidogrel/uso terapéutico , Clopidogrel/efectos adversos , Clopidogrel/administración & dosificación , Masculino , Femenino , Persona de Mediana Edad , Pronóstico , Anciano , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/efectos adversos , Genotipo , Alelos , Medicina de Precisión/métodos , Hemorragia/genéticaRESUMEN
OBJECTIVES: To assess whether genotype-guided selection of oral antiplatelet drugs using a clinical decision support (CDS) algorithm reduces the rate of major adverse cardiovascular and cerebrovascular events (MACCEs) among Caribbean Hispanic patients, after 6 months. DESIGN: An open-label, multicentre, non-randomised clinical trial. SETTING: Eight secondary and tertiary care hospitals (public and private) in Puerto Rico. PARTICIPANTS: 300 Caribbean Hispanic patients on clopidogrel, both genders, underwent percutaneous coronary intervention (PCI) for acute coronary syndromes, stable ischaemic heart disease and documented extracardiac vascular diseases. INTERVENTIONS: Patients were separated into standard-of-care (SoC) and genotype-guided (pharmacogenetic (PGx)-CDS) groups (150 each) and stratified by risk scores. Risk scores were calculated based on a previously developed CDS risk prediction algorithm designed to make actionable treatment recommendations for each patient. Individual platelet function, genotypes, clinical and demographic data were included. Ticagrelor was recommended for patients with a high-risk score ≥2 in the PGx-CDS group only, the rest were kept or de-escalated to clopidogrel. The intervention took place within 3-5 days after PCI. Adherence medication score was also measured. PRIMARY AND SECONDARY OUTCOMES: The occurrence rate of MACCEs (primary) and bleeding episodes (secondary). Statistical associations between patient time free of events and predictor variables (ie, treatment groups, risk scores) were tested using Kaplan-Meier survival analyses and Cox proportional-hazards regression models. RESULTS: The genotype-guided group had a clinically lower but not significantly different risk of MACCEs compared with the SoC group (8.7% vs 10.7%, p=0.56; HR=0.56). Among high-risk score patients, genotype-driven guidance of antiplatelet therapy showed superiority over SoC in reducing MACCE incidence 6 months postcoronary stenting (adjusted HR=0.104; p< 0.0001). CONCLUSIONS: The potential benefit of implementing our PGx-CDS algorithm to significantly reduce the incidence rate of MACCEs in post-PCI Caribbean Hispanic patients on clopidogrel was observed exclusively among high-risk patients, with apparently no evident effect in other patient groups. TRIAL REGISTRATION NUMBER: NCT03419325.
Asunto(s)
Algoritmos , Clopidogrel , Hispánicos o Latinos , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria , Ticagrelor , Humanos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Clopidogrel/uso terapéutico , Puerto Rico , Anciano , Ticagrelor/uso terapéutico , Síndrome Coronario Agudo/tratamiento farmacológico , Síndrome Coronario Agudo/genética , Síndrome Coronario Agudo/terapia , Sistemas de Apoyo a Decisiones Clínicas , Genotipo , Farmacogenética , Citocromo P-450 CYP2C19/genética , Medición de Riesgo , Región del Caribe/etnología , Hemorragia/inducido químicamenteRESUMEN
Background: Stroke or transient ischaemic attack patients are at increased risk of secondary vascular events. Antiplatelet medications, most commonly clopidogrel, are prescribed to reduce this risk. Factors including CYP2C19 genetic variants can hinder clopidogrel metabolism. Laboratory-based or point-of-care tests can detect these variants, enabling targeted treatment. Objective: To assess the effectiveness of genetic testing to identify clopidogrel resistance in people with ischaemic stroke or transient ischaemic attack. Specific objectives: Do people tested for clopidogrel resistance, and treated accordingly, have a reduced risk of secondary vascular events? Do people with loss-of-function alleles associated with clopidogrel resistance have a reduced risk of secondary vascular events if treated with alternative interventions compared to clopidogrel? Do people with loss-of-function alleles associated with clopidogrel resistance have an increased risk of secondary vascular events when treated with clopidogrel? What is the accuracy of point-of-care tests for detecting variants associated with clopidogrel resistance? What is the technical performance and cost of CYP2C19 genetic tests? Is genetic testing for clopidogrel resistance cost-effective compared with no testing? Design: Systematic review and economic model. Results: Objective 1: Two studies assessed secondary vascular events in patients tested for loss-of-function alleles and treated accordingly. They found a reduced risk, but confidence intervals were wide (hazard ratio 0.50, 95% confidence interval 0.09 to 2.74 and hazard ratio 0.53, 95% confidence interval 0.24 to 1.18). Objective 2: Seven randomised controlled trials compared clopidogrel with alternative treatment in people with genetic variants. Ticagrelor was associated with a lower risk of secondary vascular events than clopidogrel (summary hazard ratio 0.76, 95% confidence interval 0.65 to 0.90; two studies). Objective 3: Twenty-five studies compared outcomes in people with and without genetic variants treated with clopidogrel. People with genetic variants were at an increased risk of secondary vascular events (hazard ratio 1.72, 95% confidence interval 1.43 to 2.08; 18 studies). There was no difference in bleeding risk (hazard ratio 0.98, 95% confidence interval 0.68 to 1.40; five studies). Objective 4: Eleven studies evaluated Genomadix Cube accuracy; no studies evaluated Genedrive. Summary sensitivity and specificity against laboratory reference standards were both 100% (95% confidence interval 94% to 100% and 99% to 100%). Objective 5: Seventeen studies evaluated technical performance of point-of-care tests. Test failure rate ranged from 0.4% to 19% for Genomadix Cube. A survey of 8/10 genomic laboratory hubs revealed variation in preferred technologies for testing, and cost per test ranging from £15 to £250. Most laboratories expected test failure rate to be < 1%. Additional resources could enhance testing capacity and expedite turnaround times. Objective 6: Laboratory and point-of-care CYP2C19 testing strategies were cost-saving and increase quality-adjusted life-years compared with no testing. Both strategies gave similar costs, quality-adjusted life-years and expected net monetary benefit. Conclusions: Our results suggest that CYP2C19 testing followed by tailored treatment is likely to be effective and cost-effective in both populations. Future work: Accuracy and technical performance of Genedrive. Test failure rate of Genomadix Cube in a National Health Service setting. Value of testing additional loss-of-function alleles. Appropriateness of treatment dichotomy based on loss-of-function alleles. Limitations: Lack of data on Genedrive. No randomised 'test-and-treat' studies of dipyramidole plus aspirin. Study registration: This study is registered as PROSPERO CRD42022357661. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Evidence Synthesis programme (NIHR award ref: NIHR135620) and is published in full in Health Technology Assessment; Vol. 28, No. 57. See the NIHR Funding and Awards website for further award information.
The most common type of stroke occurs when the supply of blood to the brain is cut off. Symptoms of stroke happen suddenly and vary depending on which part of the brain is affected. They usually include problems with movement, speech, vision and the face drooping on one side. A 'transient ischaemic attack' is a milder related condition. There are around 100,000 strokes and 60,000 transient ischaemic attacks every year in the UK. People who have a stroke or transient ischaemic attack are at greater risk of having another stroke. To reduce the chances of this happening, doctors will often prescribe medication. The most common medication used is called 'clopidogrel'. However, clopidogrel does not work for everyone. One reason for this is having specific variations of a gene called the CYP2C19 gene. Around one in three people in the UK have this variation. We wanted to know whether introducing genetic testing to identify variations in the CYP2C19 gene for people who have had a stroke or transient ischaemic attack can help doctors prescribe a treatment that will work for them, reducing the risk of having another stroke. We also wanted to know if doing this test would be a good use of NHS money. Doing a genetic test to identify variations in the CYP2C19 gene, and prescribing an alternative medication for people with these variations, may reduce the chances of having a new stroke. It is likely that a genetic test for variations of the CYP2C19 gene would represent value for money for the NHS.
Asunto(s)
Clopidogrel , Análisis Costo-Beneficio , Citocromo P-450 CYP2C19 , Resistencia a Medicamentos , Ataque Isquémico Transitorio , Inhibidores de Agregación Plaquetaria , Clopidogrel/uso terapéutico , Humanos , Ataque Isquémico Transitorio/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Citocromo P-450 CYP2C19/genética , Resistencia a Medicamentos/genética , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Genotipo , Modelos Económicos , Pruebas Genéticas , Años de Vida Ajustados por Calidad de VidaRESUMEN
Dual antiplatelet therapy (DAPT) use is the standard of practice after flow diversion (FD) for intracranial aneurysms (IAs). Yet, no consensus exists in the literature regarding the optimal regimen. Certain institutions utilize various platelet function testing (PFT) to assess patient responsiveness to DAPT. Clopidogrel is the most commonly prescribed drug during DAPT; however, up to 52% of patients can be non-responders, justifying PFT use. Additionally, prices vary significantly among antiplatelet drugs, often further complicated by insurance restrictions. We aimed to determine the most cost-effective strategy for deciding DAPT regimens for patients after IA treatment. A decision tree with Monte Carlo simulations was performed to simulate patients undergoing various three-month postoperative DAPT regimens. Patients were either universally administered aspirin alongside clopidogrel, ticagrelor, or prasugrel without PFT, or administered one of the former thienopyridine medications based on platelet reactivity unit (PRU) results after clopidogrel. Input data for the model were extracted from the current literature, and the willingness-to-pay threshold (WTP) was defined as $100,000 per QALY as per standard practice in the US. The baseline comparison was with universal clopidogrel DAPT without any PFT. Probabilistic and deterministic sensitivity analyses were performed to evaluate the robustness of the model. Utilizing PFT and switching clopidogrel to prasugrel if resistance is documented was the most cost-effective regimen compared to universal clopidogrel, with a base-case incremental cost-effectiveness ratio (ICER) of $-35,255 (cost $2,336.67, effectiveness 0.85). Performing PFT and switching clopidogrel to ticagrelor (ICER $-4,671; cost $2,995.06, effectiveness 0.84), universal prasugrel (ICER $5,553; cost $3,097.30, effectiveness 0.84), or universal ticagrelor (ICER $75,969; cost $3,801.36, effectiveness 0.84) were all more cost-effective than treating patients with universal clopidogrel (cost $3,041.77, effectiveness 0.83). These conclusions remain robust in probabilistic and deterministic sensitivity analyses. The most cost-effective strategy guiding DAPT after FD for IAs is to perform PFTs and switch clopidogrel to prasugrel if resistance is documented, alongside aspirin. The cost of PFT is strongly justified and recommended when deciding patient-specific DAPT regimens.
Asunto(s)
Análisis Costo-Beneficio , Aneurisma Intracraneal , Inhibidores de Agregación Plaquetaria , Pruebas de Función Plaquetaria , Humanos , Aneurisma Intracraneal/cirugía , Aneurisma Intracraneal/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/economía , Clopidogrel/uso terapéutico , Clopidogrel/economía , Clorhidrato de Prasugrel/uso terapéutico , Clorhidrato de Prasugrel/economía , Aspirina/uso terapéutico , Aspirina/economía , Ticagrelor/uso terapéutico , Terapia Antiplaquetaria Doble/métodosRESUMEN
Currently, the standard treatment for patients who have undergone percutaneous coronary intervention (PCI) following acute myocardial infarction (MI) involves dual antiplatelet therapy (DAPT) with a combination of aspirin and a potent P2Y12 receptor inhibitor. However, the potential benefits of aspirin were partially constrained by the intolerance of some patients. The safety and efficacy of indobufen, an alternative antiplatelet agents to aspirin, in patients with AMI after PCI are yet to be thoroughly investigated.This retrospective study was conducted at a single center and utilized propensity score matching. The enrollment spanned from January 2019 to June 2022, incorporating patients with AMI after PCI. The participants were categorized into two groups based on discharged prescriptions: the aspirin DAPT group and the indobufen DAPT group. The primary endpoint focused on net adverse clinical event (NACE), defined as a composite outcome, including cardiac death, recurrence of MI, definite or probable stent thrombosis (ST), target lesion revascularization (TLR), ischemic stroke and Bleeding Academic Research Consortium (BARC) criteria type 2, 3, or 5. All the patients underwent a one-year follow-up period.A total of 1451 patients were enrolled in this study, with 258 assigned to the indobufen DAPT group and 1193 to the aspirin DAPT group. Following 1:1 propensity score matching, 224 patients were retained in each group. In the indobufen DAPT group, 58 individuals (25.9%) experienced the primary endpoint within one year, compared to 52 individuals (23.2%) in the aspirin DAPT group (HR 1.128, 95% CI 0.776-1.639, p = .527). Specifically, no significant differences were observed in either the efficacy endpoint (MACCE, 20.1% vs. 14.7%, HR 1.392, 95% CI 0.893-2.170, p = .146) or the safety endpoint (BARC 2,3 or 5, 8.04% vs. 10.30%, HR 0.779, p = .427). These findings remained consistent at 1, 3, or 6 months. Additionally, the incidence of gastrointestinal symptoms were significantly lower in indobufen DAPT group compared to the aspirin DAPT group (7.1% vs. 14.3%, p = .022).Our research reveals that the efficacy and safety of indobufen are comparable to aspirin in Chinese patients with AMI following PCI. Given the potential advantages of indobufen in alleviating gastrointestinal symptoms, we propose it as a viable alternative for individuals intolerant to aspirin.
What is the context? Currently, the standard treatment for patients who have undergone percutaneous coronary intervention following acute myocardial infarction involves dual antiplatelet therapy with a combination of aspirin and a potent P2Y12 receptor inhibitor.However, the potential benefits of aspirin were partially constrained by the intolerance of some patients.The safety and efficacy of indobufen, an alternative antiplatelet agents to aspirin, in patients with AMI after PCI are yet to be thoroughly investigated.What is new? While both American and European clinical guidelines recommend the use of indobufen as an alternative treatment for patients who cannot tolerate aspirin, there exists a limited body of research on this subject.Our research is the first to address this gap by comparing the efficacy and safety of indobufen and aspirin in patients with AMI.Our research reveals that the efficacy and safety of indobufen are comparable to aspirin in Chinese patients with AMI following PCI. Given the potential advantages of indobufen in alleviating gastrointestinal symptoms, we propose it as a viable alternative for individuals intolerant to aspirin.What is the impact? These findings might pave the way for further exploration of alternatives to aspirin in patients with AMI.
Asunto(s)
Aspirina , Clopidogrel , Infarto del Miocardio , Intervención Coronaria Percutánea , Humanos , Intervención Coronaria Percutánea/métodos , Aspirina/uso terapéutico , Masculino , Femenino , Clopidogrel/uso terapéutico , Persona de Mediana Edad , Estudios Retrospectivos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/farmacología , Anciano , Resultado del Tratamiento , Quimioterapia Combinada/métodosRESUMEN
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.
Asunto(s)
Anticoagulantes , Inhibidores de Agregación Plaquetaria , Humanos , Anticoagulantes/uso terapéutico , Femenino , Masculino , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/efectos adversos , Persona de Mediana Edad , Tiempo de Sangría , Hemorragia Bucal/prevención & control , Hemorragia Bucal/etiología , Anciano , Adulto , Higiene Bucal , Dabigatrán/uso terapéutico , Dabigatrán/efectos adversos , Inhibidores del Factor Xa/uso terapéutico , Warfarina/uso terapéutico , Warfarina/efectos adversos , Clopidogrel/uso terapéutico , Clopidogrel/efectos adversos , Pirazoles/uso terapéutico , Aspirina/efectos adversos , Aspirina/uso terapéutico , Rivaroxabán/uso terapéutico , Rivaroxabán/efectos adversosRESUMEN
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.
Asunto(s)
Fibrilación Atrial , Clopidogrel , Puente de Arteria Coronaria Off-Pump , Inhibidores de Agregación Plaquetaria , Ticagrelor , Humanos , Clopidogrel/uso terapéutico , Clopidogrel/efectos adversos , Ticagrelor/uso terapéutico , Fibrilación Atrial/etiología , Fibrilación Atrial/epidemiología , Fibrilación Atrial/prevención & control , Fibrilación Atrial/diagnóstico , Masculino , Femenino , Puente de Arteria Coronaria Off-Pump/efectos adversos , Persona de Mediana Edad , Anciano , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , Incidencia , Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP2C19/metabolismo , Estudios Prospectivos , Agregación Plaquetaria/efectos de los fármacos , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Antagonistas del Receptor Purinérgico P2Y/efectos adversos , Enfermedad de la Arteria Coronaria/cirugía , Resultado del TratamientoRESUMEN
BACKGROUND: Treatment of isolated and non-obstructive atherosclerotic coronary artery ectasia (CAE) is still controversial. AIM: To assess the efficacy and safety of vitamin-K antagonist (VKA) versus dual antiplatelet (DAPT) therapy in management of patients with isolated and non-obstructive atherosclerotic CAE. METHODS: We prospectively enrolled 79 patients diagnosed on elective coronary angiography to have either isolated CAE or non-obstructive atherosclerotic CAE. Patients were assigned in 1:1 pattern to receive either VKA (warfarin) or DAPT (aspirin plus clopidogrel). Patients were followed-up for nine-months. The primary endpoint was the cumulative events rate including acute coronary event, target vessel intervention, or cardiac death. Analysis of cumulative events at different time intervals, its individual components, and bleeding were considered secondary endpoints. RESULTS: Cumulative events rate was 33%, with mortality rate of 2.5%. Both treatment groups showed comparable cumulative events during the nine-months follow-up duration. Nevertheless, Kaplan-Meier analysis beyond the first 3-months of follow-up showed significantly higher event-free survival among the VKA-group. Recurrent events (≥2) were significantly higher among the DAPT-group. Both groups showed no major bleeding events. Multivariable cox-regression analysis showed that presence of significant coronary tortuosity, use of DAPT in reference to VKA, and lower percent time in therapeutic range (%TTR) among those receiving VKA were significant independent predictors of clinical adverse events beyond the first 3-months of follow-up. CONCLUSION: Cumulative adverse events were comparable among both treatment groups for isolated non-obstructive CAE. However, adverse events were significantly more frequent in the DAPT-group beyond the first three months.
Asunto(s)
Enfermedad de la Arteria Coronaria , Terapia Antiplaquetaria Doble , Inhibidores de Agregación Plaquetaria , Vitamina K , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Anciano , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Vitamina K/antagonistas & inhibidores , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Estudios de Seguimiento , Terapia Antiplaquetaria Doble/métodos , Resultado del Tratamiento , Angiografía Coronaria , Dilatación Patológica , Aspirina/uso terapéutico , Aspirina/administración & dosificación , Clopidogrel/uso terapéutico , Clopidogrel/administración & dosificación , Anticoagulantes/uso terapéutico , Anticoagulantes/administración & dosificación , Manejo de la Enfermedad , Warfarina/uso terapéutico , Warfarina/administración & dosificación , Warfarina/efectos adversosRESUMEN
For many years, clopidogrel has been a commonly utilised antiplatelet drug in the management of coronary artery disease (CAD). It's thought that the CYP2C19 loss of function (LoF) polymorphism causes clopidogrel's poor metabolism, which eventually leads to resistance. Previous research produced extremely divergent and inconsistent results, making it impossible to draw definitive conclusions. Therefore, current, investigation was carried out to obtain definitive evidence from an updated meta-analysis on the connection between CYP2C19 LoF polymorphism and coronary artery event in patients treated with clopidogrel. 52,542 individuals with coronary artery disease who were receiving clopidogrel treatment were included in 87 carefully chosen trials from reliable databases that we used for our meta-analysis. According to our data, those who carry one or more CYP2C19 LoF alleles worldwide are much more likely to experience composite events and coronary artery events than people who do not carry these alleles, especially in Asian populations. Our meta-analysis observed that the global population, particularly Asians receiving clopidogrel treatment, is at risk of recurrent coronary artery events and composite events if they carry the CYP2C19 LoF alleles. Additional research is essential on alternative antiplatelet therapies for individuals who exhibit poor or intermediate metabolic activity. OBJECTIVES: 1.To systematically analyze the current evidence regarding the association of CYP2C19 variants with coronary artery disease (CAD). 2.To conduct a meta-analysis to investigate the association between loss of function (LoF) CYP2C19 modifications and CAD.
Asunto(s)
Clopidogrel , Enfermedad de la Arteria Coronaria , Citocromo P-450 CYP2C19 , Inhibidores de Agregación Plaquetaria , Humanos , Citocromo P-450 CYP2C19/genética , Clopidogrel/uso terapéutico , Enfermedad de la Arteria Coronaria/genética , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Resultado del Tratamiento , Mutación con Pérdida de FunciónRESUMEN
PURPOSE: Antiplatelet therapy is used for the primary and secondary prevention of thrombotic diseases such as acute coronary syndrome (ACS). These patients are more vulnerable to infections, as such, strategies are required to mitigate these risks. METHODS: We conducted a retrospective cohort study using TriNetX, a global federated health research network that includes both inpatient and outpatient electronic medical records from health care organizations worldwide. Patients ≥18 years old, after ACS, who were placed on aspirin and ticagrelor were compared with patients placed on aspirin and clopidogrel or prasugrel. Patients were identified using International Statistical Classification of Diseases and Related Health Problems terminology codes. After propensity score matching (1:1), a total of 239,358 patients were identified in each cohort. The primary outcomes of interest investigated were rates of (1) acute and subacute infective endocarditis, (2) sepsis of unknown origin, (3) staphylococcus arthritis, (4) cellulitis and acute lymphangitis, (5) Staphylococcus aureus bacteremia, and (6) staphylococcal pneumonia after initiation of treatment. Outcomes were analyzed at 1, 3, and 5 years. FINDINGS: At 5 years, a combination of aspirin and ticagrelor, compared with a combination of aspirin and clopidogrel or prasugrel, was associated with significantly reduced rates of (1) acute and subacute endocarditis (hazard ratio [HR] plus 95% CI) (HR = 0.85; 0.77-0.945; P = 0.030), (2) sepsis of unknown origin (HR = 0.89; 95% CI, 0.86-0.91; P < 0.0001), (3) cellulitis and acute lymphangitis (HR = 0.89; 95% CI, 0.87-0.92; P < 0.0001, and (4) Staphylococcus aureus bacteremia (HR = 0.72; 95% CI, 0.61-0.85; P = 0.0007). However, a combination of aspirin and clopidogrel was associated with a marinally lower risk of staphylococcal pneumonia (HR = 1.04; 95% CI, 1.01-1.062; P < 0.0001). IMPLICATIONS: A combination of aspirin and ticagrelor is associated with a lower rate of a variety of bacterial infections. This combination warrants further investigation in in-vitro studies to tease out mechanisms and through clinical randomized trials in groups who have ACS and are at high infection risk.
Asunto(s)
Aspirina , Clopidogrel , Inhibidores de Agregación Plaquetaria , Clorhidrato de Prasugrel , Infecciones Estafilocócicas , Ticagrelor , Humanos , Ticagrelor/uso terapéutico , Ticagrelor/administración & dosificación , Aspirina/administración & dosificación , Aspirina/uso terapéutico , Femenino , Masculino , Estudios Retrospectivos , Clopidogrel/uso terapéutico , Clopidogrel/administración & dosificación , Clorhidrato de Prasugrel/uso terapéutico , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/efectos adversos , Anciano , Infecciones Estafilocócicas/tratamiento farmacológico , Síndrome Coronario Agudo/tratamiento farmacológico , Quimioterapia CombinadaRESUMEN
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.
Asunto(s)
Síndrome Coronario Agudo , Aspirina , Clopidogrel , Stents Liberadores de Fármacos , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria , Humanos , Síndrome Coronario Agudo/terapia , Clopidogrel/uso terapéutico , Clopidogrel/administración & dosificación , Clopidogrel/efectos adversos , Aspirina/administración & dosificación , Aspirina/uso terapéutico , Aspirina/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/efectos adversos , Intervención Coronaria Percutánea/métodos , Intervención Coronaria Percutánea/efectos adversos , Terapia Antiplaquetaria Doble/métodos , Resultado del Tratamiento , Hemorragia/inducido químicamenteRESUMEN
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.