RESUMEN

Dual antiplatelet therapy with aspirin and a P2Y12 inhibitor is fundamental in all patients undergoing percutaneous coronary intervention (PCI) to prevent coronary thrombosis. In patients with atrial fibrillation (AF), an oral anticoagulant gives protection against ischemic stroke or systemic embolism. AF-PCI patients are at high bleeding risk and decision-making regarding the optimal antithrombotic therapy remains challenging. Dual antithrombotic therapy (DAT) has been shown to reduce bleeding events but at the cost of a higher risk of stent thrombosis. Further studies are needed to clarify the optimal duration of triple antithrombotic therapy (TAT) or DAT and the role of more potent antiplatelet drugs.

Asunto(s)

Anticoagulantes , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria , Humanos , Intervención Coronaria Percutánea/métodos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/uso terapéutico , Anticoagulantes/administración & dosificación , Anticoagulantes/uso terapéutico , Administración Oral , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Enfermedad de la Arteria Coronaria/cirugía , Terapia Antiplaquetaria Doble/métodos , Hemorragia/inducido químicamente , Hemorragia/prevención & control , Trombosis Coronaria/prevención & control

RESUMEN

The antithrombotic management of chronic coronary syndrome (CCS) involves a 6-month course of dual antiplatelet therapy (DAPT), followed by chronic aspirin therapy. In patients with a baseline indication for anticoagulation, a variable duration of triple antithrombotic therapy is administered, followed by dual antithrombotic therapy until the sixth month post-percutaneous coronary intervention (PCI), and ultimately a transition to chronic anticoagulation. However, advancements in stent technology reducing the risk of stent thrombosis and a growing focus on the impact of bleeding on prognosis have prompted the development of new therapeutic strategies. These strategies aim to enhance protection against ischemic events in the initial stages after PCI while mitigating the risk of bleeding in the long term. This article delineates the therapeutic strategies outlined in European and American guidelines for CCS management, with special attention to investigational strategies.

Asunto(s)

Fibrinolíticos , Intervención Coronaria Percutánea , Humanos , Intervención Coronaria Percutánea/métodos , Fibrinolíticos/uso terapéutico , Fibrinolíticos/administración & dosificación , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Enfermedad Crónica , Anticoagulantes/uso terapéutico , Anticoagulantes/administración & dosificación , Terapia Antiplaquetaria Doble/métodos

RESUMEN

BACKGROUND: Dual antiplatelet therapy (DAPT) for 12 months is the standard of care after coronary stenting in patients with acute coronary syndrome (ACS). The aim of this individual patient-level meta-analysis was to summarise the evidence comparing DAPT de-escalation to ticagrelor monotherapy versus continuing DAPT for 12 months after coronary drug-eluting stent implantation. METHODS: A systematic review and individual patient data (IPD)-level meta-analysis of randomised trials with centrally adjudicated endpoints was performed to evaluate the comparative efficacy and safety of ticagrelor monotherapy (90 mg twice a day) after short-term DAPT (from 2 weeks to 3 months) versus 12-month DAPT in patients undergoing percutaneous coronary intervention with a coronary drug-eluting stent. Randomised trials comparing P2Y12 inhibitor monotherapy with DAPT after coronary revascularisation were searched in Ovid MEDLINE, Embase, and two websites (www.tctmd.com and www.escardio.org) from database inception up to May 20, 2024. Trials that included patients with an indication for long-term oral anticoagulants were excluded. The risk of bias was assessed using the revised Cochrane risk-of-bias tool. The principal investigators of the eligible trials provided IPD by means of an anonymised electronic dataset. The three ranked coprimary endpoints were major adverse cardiovascular or cerebrovascular events (MACCE; a composite of all-cause death, myocardial infarction, or stroke) tested for non-inferiority in the per-protocol population; and Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding and all-cause death tested for superiority in the intention-to-treat population. All outcomes are reported as Kaplan-Meier estimates. The non-inferiority was tested using a one-sided α of 0·025 with the prespecified non-inferiority margin of 1·15 (hazard ratio [HR] scale), followed by the ranked superiority testing at a two-sided α of 0·05. This study is registered with PROSPERO (CRD42024506083). FINDINGS: A total of 8361 unique citations were screened, of which 610 records were considered potentially eligible during the screening of titles and abstracts. Of these, six trials that randomly assigned patients to ticagrelor monotherapy or DAPT were identified. De-escalation took place a median of 78 days (IQR 31-92) after intervention, with a median duration of treatment of 334 days (329-365). Among 23 256 patients in the per-protocol population, MACCE occurred in 297 (Kaplan-Meier estimate 2·8%) with ticagrelor monotherapy and 332 (Kaplan-Meier estimate 3·2%) with DAPT (HR 0·91 [95% CI 0·78-1·07]; p=0·0039 for non-inferiority; τ2<0·0001). Among 24 407 patients in the intention-to-treat population, the risks of BARC 3 or 5 bleeding (Kaplan-Meier estimate 0·9% vs 2·1%; HR 0·43 [95% CI 0·34-0·54]; p<0·0001 for superiority; τ2=0·079) and all-cause death (Kaplan-Meier estimate 0·9% vs 1·2%; 0·76 [0·59-0·98]; p=0·034 for superiority; τ2<0·0001) were lower with ticagrelor monotherapy. Trial sequential analysis showed strong evidence of non-inferiority for MACCE and superiority for bleeding among the overall and ACS populations (the z-curve crossed the monitoring boundaries or the required information size without crossing the futility boundaries or approaching the null). The treatment effects were heterogeneous by sex for MACCE (p interaction=0·041) and all-cause death (p interaction=0·050), indicating a possible benefit in women with ticagrelor monotherapy, and by clinical presentation for bleeding (p interaction=0·022), indicating a benefit in ACS with ticagrelor monotherapy. INTERPRETATION: Our study found robust evidence that, compared with 12 months of DAPT, de-escalation to ticagrelor monotherapy does not increase ischaemic risk and reduces the risk of major bleeding, especially in patients with ACS. Ticagrelor monotherapy might also be associated with a mortality benefit, particularly among women, which warrants further investigation. FUNDING: Cardiocentro Ticino Institute, Ente Ospedaliero Cantonale.

Asunto(s)

Síndrome Coronario Agudo , Terapia Antiplaquetaria Doble , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria , Ensayos Clínicos Controlados Aleatorios como Asunto , Ticagrelor , Humanos , Ticagrelor/uso terapéutico , Ticagrelor/administración & dosificación , Síndrome Coronario Agudo/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Terapia Antiplaquetaria Doble/métodos , Hemorragia/inducido químicamente , Stents Liberadores de Fármacos , Resultado del Tratamiento

Asunto(s)

Síndrome Coronario Agudo , Hemorragia , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria , Humanos , Intervención Coronaria Percutánea/efectos adversos , Síndrome Coronario Agudo/terapia , Hemorragia/inducido químicamente , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Terapia Antiplaquetaria Doble/efectos adversos , Terapia Antiplaquetaria Doble/métodos , Factores de Riesgo , Resultado del Tratamiento , Factores de Tiempo

RESUMEN

BACKGROUND: Patients undergoing percutaneous coronary intervention mainly receive antiplatelet therapy. However, limited data are available regarding the optimal dual antiplatelet therapy (DAPT) following the implantation of new-generation drug-eluting stent (DES). OBJECTIVE: This study aimed to compare the clinical outcomes of short-term (1-3 months) DAPT and standard (12 months) DAPT after the implantation of a new-generation of DES. METHODS: We systematically searched PubMed, The Cochrane Library Database, Embase for trials that compared short-term (1-3 months) and standard DAPT after the implantation of next-generation DES were retrieved from all published studies in English until December 31, 2021. The primary endpoint was major bleeding. The secondary endpoints included all-cause mortality, cardiac death, myocardial infarction, stroke, stent thrombosis, and all bleeding. RESULTS: This study included a total of 7 randomized controlled trials, comprising 28,344 subjects. Regarding primary endpoints, short-term DAPT exhibited a significantly lower incidence of major bleeding compared with standard DAPT [relative risk (RR): 0.66, 95% confidence interval (CI): (0.54, 0.81), P < .0001]. For secondary endpoints, there were significant differences between short-term and standard DAPT in all bleeding [RR: 0.59, 95% CI: (0.50, 0.69), P < .00001]. However, no significant differences were identified in all-cause mortality [RR: 0.96, 95% CI: (0.77, 1.18), P = .27], myocardial infarction [RR: 0.98, 95% CI: (0.82, 1.18), P = .86], cardiac death [RR: 0.83, 95% CI: (0.63, 1.10), P = .20], stroke [RR: 1.08, 95% CI: (0.79, 1.47), P = .63], cerebrovascular [RR: 1.08, 95% CI: (0.79, 1.47), P = .63], and stent thrombosis [RR: 1.13, 95% CI: (0.80, 1.57), P = .49] between the 2 groups. CONCLUSION: In patients undergoing implantation of a new-generation of DES, short-term (1-3 months) DAPT exhibited no inferiority compared with standard (12 months) DAPT in terms of all-cause mortality, cardiac death, myocardial infarction, stroke, and definite or probable stent thrombosis compared with standard (12 months) DAPT. However, short-term DAPT appeared superior to standard DAPT in terms of major bleeding and all bleeding.

Asunto(s)

Stents Liberadores de Fármacos , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Intervención Coronaria Percutánea/métodos , Terapia Antiplaquetaria Doble/métodos , Hemorragia/epidemiología , Hemorragia/inducido químicamente , Hemorragia/prevención & control

RESUMEN

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 Combinada

RESUMEN

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 Tratamiento

Asunto(s)

Ataque Isquémico Transitorio , Accidente Cerebrovascular Isquémico , Inhibidores de Agregación Plaquetaria , Humanos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Ataque Isquémico Transitorio/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Terapia Antiplaquetaria Doble/métodos , Factores de Tiempo , Accidente Cerebrovascular/tratamiento farmacológico

RESUMEN

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/métodos

RESUMEN

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.

Asunto(s)

Clopidogrel , Citocromo P-450 CYP2C19 , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria , Clorhidrato de Prasugrel , Medicina de Precisión , Sistema de Registros , Ticagrelor , Humanos , Intervención Coronaria Percutánea/efectos adversos , Citocromo P-450 CYP2C19/genética , Medicina de Precisión/métodos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/efectos adversos , Clopidogrel/administración & dosificación , Clopidogrel/efectos adversos , Ticagrelor/administración & dosificación , Ticagrelor/uso terapéutico , Clorhidrato de Prasugrel/administración & dosificación , Clorhidrato de Prasugrel/uso terapéutico , Clorhidrato de Prasugrel/efectos adversos , Terapia Antiplaquetaria Doble/métodos , Aspirina/administración & dosificación , Aspirina/efectos adversos , Aspirina/uso terapéutico , Antagonistas del Receptor Purinérgico P2Y/administración & dosificación , Antagonistas del Receptor Purinérgico P2Y/efectos adversos , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Hemorragia/inducido químicamente , Hemorragia/prevención & control

RESUMEN

BACKGROUND: The optimal treatment for acute minor ischemic stroke is still undefined. and options include dual antiplatelet treatment (DAPT), intravenous thrombolysis (IVT), or their combination. We aimed to investigate benefits and risks of combining IVT and DAPT versus DAPT alone in patients with MIS. METHODS AND RESULTS: This is a prespecified propensity score-matched analysis from a prospective multicentric real-world study (READAPT [Real-Life Study on Short-Term Dual Antiplatelet Treatment in Patients With Ischemic Stroke or Transient Ischemic Attack]). We included patients with MIS (National Institutes of Health Stroke Scale score at admission ≤5), without prestroke disability (modified Rankin scale [mRS] score ≤2). The primary outcomes were 90-day mRS score of 0 to 2 and ordinal mRS distribution. The secondary outcomes included 90-day risk of stroke and other vascular events and 24-hour early neurological improvement or deterioration (≥2-point National Institutes of Health Stroke Scale score decrease or increase from the baseline, respectively). From 1373 patients with MIS, 240 patients treated with IVT plus DAPT were matched with 427 patients treated with DAPT alone. At 90 days, IVT plus DAPT versus DAPT alone showed similar frequency of mRS 0 to 2 (risk difference, 2.3% [95% CI -2.0% to 6.7%]; P=0.295; risk ratio, 1.03 [95% CI 0.98-1.08]; P=0.312) but more favorable ordinal mRS scores distribution (odds ratio, 0.57 [95% CI 0.41-0.79]; P<0.001). Compared with patients treated with DAPT alone, those combining IVT and DAPT had higher 24-hour early neurological improvement (risk difference, 20.9% [95% CI 13.1%-28.6%]; risk ratio, 1.59 [95% CI 1.34-1.89]; both P<0.001) and lower 90-day risk of stroke and other vascular events (hazard ratio, 0.27 [95% CI 0.08-0.90]; P=0.034). There were no differences in safety outcomes. CONCLUSIONS: According to findings from this observational study, patients with MIS may benefit in terms of better functional outcome and lower risk of recurrent events from combining IVT and DAPT versus DAPT alone without safety concerns. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05476081.

Asunto(s)

Terapia Antiplaquetaria Doble , Accidente Cerebrovascular Isquémico , Inhibidores de Agregación Plaquetaria , Puntaje de Propensión , Terapia Trombolítica , Humanos , Femenino , Masculino , Accidente Cerebrovascular Isquémico/diagnóstico , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Anciano , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/efectos adversos , Terapia Trombolítica/métodos , Terapia Trombolítica/efectos adversos , Estudios Prospectivos , Terapia Antiplaquetaria Doble/métodos , Persona de Mediana Edad , Resultado del Tratamiento , Fibrinolíticos/administración & dosificación , Fibrinolíticos/efectos adversos , Factores de Tiempo , Administración Intravenosa , Medición de Riesgo , Quimioterapia Combinada , Anciano de 80 o más Años , Factores de Riesgo

RESUMEN

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 adversos

RESUMEN

BACKGROUND: The prevalence of and outcomes associated with different antithrombotic strategies after left atrial appendage occlusion (LAAO) are not well described. OBJECTIVES: This study sought to evaluate patterns of antithrombotic medication strategies at discharge following LAAO with the Watchman FLX device in real-world practice and to compare the risk of adverse events among the different antithrombotic regimens. METHODS: The authors evaluated patients in the NCDR (National Cardiovascular Data Registry) LAAO Registry who underwent LAAO with the second-generation LAA closure device between 2020 and 2022. They grouped patients by mutually exclusive discharge antithrombotic strategies and compared the rates of adverse events at 45 days and 6 months using multivariable Cox proportional hazards regression. RESULTS: Among 53,878 patients undergoing successful LAAO with the second-generation LAA closure device, the most common antithrombotic discharge regimens were direct oral anticoagulant (DOAC) plus aspirin (48.3%), DOAC alone (22.6%), dual antiplatelet therapy (8.1%), warfarin plus aspirin (7.7%), and DOAC plus P2Y12 inhibitor (4.9%). In multivariate analysis, DOAC alone had a lower rate of major adverse events and major bleeding at 45 days of follow-up compared with DOAC plus aspirin (major adverse events: HR: 0.78; 95% CI: 0.68-0.91; major bleeding: HR: 0.69; 95% CI: 0.60-0.80). These differences persisted at 6 months. Warfarin without aspirin also showed lower rates of major bleeding at both time points. No differences were seen in stroke/transient ischemic attack or device-related thrombus. CONCLUSIONS: In real-world U.S. practice, discharge on DOAC alone or warfarin alone was associated with a lower rate of adverse events compared with DOAC plus aspirin.

Asunto(s)

Anticoagulantes , Aspirina , Apéndice Atrial , Fibrilación Atrial , Inhibidores de Agregación Plaquetaria , Humanos , Apéndice Atrial/cirugía , Masculino , Femenino , Aspirina/administración & dosificación , Aspirina/efectos adversos , Aspirina/uso terapéutico , Anciano , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/complicaciones , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Sistema de Registros , Anciano de 80 o más Años , Terapia Antiplaquetaria Doble/métodos , Quimioterapia Combinada , Accidente Cerebrovascular/prevención & control , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/epidemiología , Persona de Mediana Edad

RESUMEN

BACKGROUND: Antithrombotic treatment (ATT) post-left atrial appendage occlusion (LAAO) remains controversial. Furthermore, most of the patients undergoing LAAO are at a very high bleeding risk. AIMS: This study aimed to compare a simplified versus conventional ATT after LAAO in very high bleeding risk patients. METHODS: This is a multicentre, retrospective study including very high bleeding risk patients, according to the Bleeding Academic Research Consortium (BARC) definition, who underwent LAAO. These included patients at >4% risk of BARC 3 to 5 bleeding or >1% risk of intracranial bleeding after the procedure. Two groups were established based on the discharge ATT. The simplified group included single antiplatelet treatment or no treatment, and the conventional group comprised dual antiplatelet treatment or anticoagulation (combined or not with antiplatelet therapy). RESULTS: A total of 1,135 patients were included. The mean CHA2DS2-VASc and HAS-BLED scores were 4.5±1.5 and 3.7±1.0, respectively. There were no differences in the composite endpoint (death, stroke, transient ischaemic attack, device-related thrombus or major bleeding) between the 2 groups (hazard ratio [HR] 0.81, 95% confidence interval [CI]: 0.59-1.11; p=0.188). Although the rate of major bleeding during the first year was numerically lower in the simplified group, it did not reach statistical significance (HR 0.67, 95% CI: 0.41-1.10; p=0.104). Nonetheless, patients with previous major bleeding presented a significantly lower rate of major bleeding when using the simplified treatment (HR 0.61, 95% CI: 0.36-0.99; p=0.049). CONCLUSIONS: In patients with very high bleeding risk, a simplified ATT after LAAO seems to be as effective as conventional protocols. Furthermore, patients with a history of major bleeding experienced a lower risk of major bleeding with the simplified ATT.

Asunto(s)

Apéndice Atrial , Fibrilación Atrial , Fibrinolíticos , Hemorragia , Inhibidores de Agregación Plaquetaria , Humanos , Apéndice Atrial/cirugía , Masculino , Femenino , Anciano , Estudios Retrospectivos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/efectos adversos , Anciano de 80 o más Años , Fibrinolíticos/uso terapéutico , Fibrinolíticos/efectos adversos , Hemorragia/inducido químicamente , Resultado del Tratamiento , Factores de Riesgo , Anticoagulantes/uso terapéutico , Anticoagulantes/efectos adversos , Accidente Cerebrovascular/prevención & control , Accidente Cerebrovascular/etiología , Medición de Riesgo , Terapia Antiplaquetaria Doble/métodos , Persona de Mediana Edad , Cierre del Apéndice Auricular Izquierdo

RESUMEN

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 químicamente

RESUMEN

BACKGROUND: It is well-established that thrombus aspiration during primary percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI) indicates a higher thrombus burden and necessitates more intensive antithrombotic therapy. The bidirectional association between adverse events in AMI patients and platelet reactivity is typically observed during dual antiplatelet therapy (DAPT). OBJECTIVE: To investigate platelet reactivity after DAPT in AMI patients with thrombus aspiration performed during PCI. METHODS: In this retrospective study, we examined 269 consecutive AMI patients who underwent PCI and recorded their demographic, clinical and laboratory data. The platelet reactivity was measured with thromboelastogram (TEM). RESULTS: Ultimately, 208 patients were included in this study and divided into a Thrombus Aspiration group (N = 97) and a PCI Alone group (N = 111) based on whether thrombus aspiration was performed or not. The adenosine diphosphate (ADP)-induced platelet inhibition rate in the Thrombus Aspiration group was higher than that in the PCI Alone group (P < 0.001). Furthermore, multivariate linear regression analysis revealed that the ADP-induced platelet inhibition rate was independently associated with leukocyte count, thrombus aspiration and the combination of aspirin and ticagrelor as DAPT after adjusting for potential covariates in all AMI patients. CONCLUSION: In conclusion, clinicians should exercise heightened attention towards the bleeding risk among patients undergoing PCI concomitant with Thrombus Aspiration postoperatively.

Asunto(s)

Infarto del Miocardio , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria , Humanos , Masculino , Femenino , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/efectos adversos , Persona de Mediana Edad , Infarto del Miocardio/complicaciones , Anciano , Intervención Coronaria Percutánea/métodos , Intervención Coronaria Percutánea/efectos adversos , Estudios Retrospectivos , Terapia Antiplaquetaria Doble/métodos , Aspirina/uso terapéutico , Aspirina/administración & dosificación , Trombosis/etiología , Trombosis/prevención & control , Plaquetas/efectos de los fármacos , Trombectomía/métodos

RESUMEN

Japan is one of the world's most aging societies and the number of elderly patients taking antithrombotic drugs is increasing. In recent years, dual antiplatelet therapy (DAPT), in which two antiplatelet drugs are administered, has become common in anticipation of its high therapeutic efficacy. However, there are concerns about increased bleeding complications in use of DAPT. Therefore, the goal of this study was to investigate the effects of DAPT in patients with traumatic brain injury (TBI). A prospective, multicenter, observational study was conducted from December 2019 to May 2021 to examine the effects of antithrombotic drugs and reversal drugs in 721 elderly patients with TBI. In the current study, the effect of DAPT on TBI was examined in a secondary analysis. Among the registered patients, 132 patients taking antiplatelet drugs only were divided into those treated with single antiplatelet therapy (SAPT) (n=106) and those treated with DAPT (n=26) prior to TBI. Glasgow Coma Scale (GCS) on admission, pupillary findings, course during hospitalization, and outcome were compared in the two groups. A similar analysis was performed in patients with a mild GCS of 13-15 (n=95) and a moderate to severe GCS of 3-12 (n=37) on admission. The DAPT group had significantly more males (67.0 % vs. 96.2 %), a higher severity of illness on admission, and a higher frequency of brain herniation findings on head CT (21.7 % vs. 46.2 %), resulting in significantly higher mortality (12.3 % vs. 30.8 %). The only significant factor for mortality was severity on admission. The rate of DAPT was significantly higher in patients with a moderate to severe GCS on admission, and DAPT was the only significant factor related to severity on admission. These findings suggest that the severity of injury on admission influences the outcome six months after injury, and that patients with more severe TBI on admission are more likely to have been treated with DAPT compared to SAPT.

Asunto(s)

Lesiones Traumáticas del Encéfalo , Terapia Antiplaquetaria Doble , Inhibidores de Agregación Plaquetaria , Humanos , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Lesiones Traumáticas del Encéfalo/complicaciones , Masculino , Femenino , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Anciano , Estudios Prospectivos , Anciano de 80 o más Años , Terapia Antiplaquetaria Doble/métodos , Resultado del Tratamiento , Escala de Coma de Glasgow , Persona de Mediana Edad

Asunto(s)

Síndrome Coronario Agudo , Aspirina , Terapia Antiplaquetaria Doble , Hemorragia , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria , Stents , Ticagrelor , Humanos , Ticagrelor/uso terapéutico , Ticagrelor/efectos adversos , Síndrome Coronario Agudo/terapia , Intervención Coronaria Percutánea/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/efectos adversos , Aspirina/uso terapéutico , Aspirina/efectos adversos , Aspirina/administración & dosificación , Hemorragia/inducido químicamente , Hemorragia/prevención & control , Terapia Antiplaquetaria Doble/métodos , Terapia Antiplaquetaria Doble/efectos adversos , Stents/efectos adversos , Resultado del Tratamiento , Quimioterapia Combinada , Factores de Tiempo

RESUMEN

The current guidelines for acute coronary syndrome (ACS) discourage the use of anticoagulation after percutaneous coronary intervention (PCI) without specific indications, although the recommendation is not well supported by evidence. In this post hoc analysis of the ShorT and OPtimal Duration of Dual AntiPlatelet Therapy-3 (STOPDAPT-3) trial, 30-day outcomes were compared between the 2 groups with and without post-PCI heparin administration among patients with ACS who did not receive mechanical support devices. The co-primary end points were the bleeding end point, defined as the Bleeding Academic Research Consortium type 3 or 5 bleeding, and the cardiovascular end point, defined as a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke. Among 4,088 patients with ACS, 2,339 patients (57.2%) received post-PCI heparin. The proportion of patients receiving post-PCI heparin was higher among those with ST-elevation myocardial infarction compared with others (72.3% and 38.8%, p <0.001), and among patients with intraprocedural adverse angiographic findings compared with those without (67.6% and 47.5%, p <0.001). Post-PCI heparin compared with no post-PCI heparin was associated with a significantly increased risk of the bleeding end point (4.75% and 2.52%, adjusted hazard ratio 1.69, 95% confidence interval 1.15 to 2.46, p = 0.007) and a numerically increased risk of the cardiovascular end point (3.16% and 1.72%, adjusted hazard ratio 1.56, 95% confidence interval 0.98 to 2.46, p = 0.06). Higher hourly dose or total doses of heparin were also associated with higher incidence of both bleeding and cardiovascular events within 30 days. In conclusion, post-PCI anticoagulation with unfractionated heparin was frequently implemented in patients with ACS. Post-PCI heparin use was associated with harm in terms of increased bleeding without the benefit of reducing cardiovascular events. Trial identifier: STOPDAPT-3 ClinicalTrials.gov number, NCT04609111.

Asunto(s)

Síndrome Coronario Agudo , Anticoagulantes , Heparina , Intervención Coronaria Percutánea , Humanos , Heparina/uso terapéutico , Heparina/administración & dosificación , Síndrome Coronario Agudo/tratamiento farmacológico , Síndrome Coronario Agudo/terapia , Masculino , Femenino , Anticoagulantes/uso terapéutico , Anticoagulantes/administración & dosificación , Persona de Mediana Edad , Anciano , Intervención Coronaria Percutánea/métodos , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Inhibidores de Agregación Plaquetaria/uso terapéutico , Terapia Antiplaquetaria Doble/métodos

Asunto(s)

Hemorragia , Inhibidores de Agregación Plaquetaria , Insuficiencia Renal Crónica , Humanos , Insuficiencia Renal Crónica/complicaciones , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Terapia Antiplaquetaria Doble/métodos , Factores de Riesgo