RESUMEN
The recent study by Kaiwen Wang et al., titled "Early postoperative acetylsalicylic acid administration does not increase the risk of postoperative intracranial bleeding in patients with spontaneous intracerebral hemorrhage," explores the association between postoperative intracranial bleeding (PIB) and various risk factors, including smoking, pre-hemorrhagic antiplatelet therapy, and dyslipidemia. While the study highlights that smoker, particularly women, are at increased risk for subarachnoid hemorrhage and acknowledges the risks of pre-hemorrhagic antiplatelet use, it overlooks the potential risk of PIB associated with early postoperative aspirin administration. This critique underscores the need to approach the study's findings with caution, given the broader context of aspirin's risk profile. Specifically, aspirin has been associated with a 37% higher relative risk of any intracranial hemorrhage, as indicated by other randomized trials. Additionally, the study's implications regarding the benefits of aspirin in stroke prevention must be critically evaluated, as the increased risk of intracranial bleeding may outweigh the potential benefits. This abstract emphasizes the importance of careful consideration of aspirin's adverse effects in the context of postoperative care.
Asunto(s)
Aspirina , Hemorragia Cerebral , Inhibidores de Agregación Plaquetaria , Humanos , Aspirina/efectos adversos , Aspirina/administración & dosificación , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Factores de Riesgo , Hemorragias Intracraneales , Femenino , Complicaciones Posoperatorias , Hemorragia Posoperatoria , MasculinoRESUMEN
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 & controlRESUMEN
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/métodosRESUMEN
Patients with peripheral artery disease (PAD) who undergo lower extremity revascularization (LER) are at high risk for cardiovascular and limb-related ischemic events. The role of antithrombotic therapy is to prevent thrombotic complications, but this requires balancing increased risk of bleeding events. The dual pathway inhibition (DPI) strategy including aspirin and low-dose rivaroxaban after LER has been shown to reduce major adverse cardiovascular and limb-related events without significant differences in major bleeding. There is now a need to implement the broad adoption of DPI therapy in PAD patients who have undergone LER in routine practice.
Asunto(s)
Fibrinolíticos , Enfermedad Arterial Periférica , Humanos , Enfermedad Arterial Periférica/cirugía , Fibrinolíticos/uso terapéutico , Trombosis/prevención & control , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Extremidad Inferior/irrigación sanguínea , Extremidad Inferior/cirugía , Hemorragia/inducido químicamente , Hemorragia/prevención & control , Aspirina/uso terapéutico , Aspirina/administración & dosificación , Rivaroxabán/uso terapéutico , Rivaroxabán/administración & dosificaciónRESUMEN
Early mechanical reperfusion, primarily via percutaneous coronary intervention, combined with timely antithrombotic drug administration, constitutes the main approach for managing acute coronary syndrome (ACS). Clinicians have access to a variety of antithrombotic agents, necessitating careful selection to balance reducing thrombotic events against increased bleeding risks. This review offers a comprehensive update on current antithrombotic therapy in ACS, emphasizing the need for individualized treatment strategies.
Asunto(s)
Síndrome Coronario Agudo , Fibrinolíticos , Intervención Coronaria Percutánea , Humanos , Síndrome Coronario Agudo/tratamiento farmacológico , Síndrome Coronario Agudo/cirugía , Fibrinolíticos/uso terapéutico , Intervención Coronaria Percutánea/métodos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Anticoagulantes/uso terapéutico , Anticoagulantes/administración & dosificación , Hemorragia/inducido químicamente , Hemorragia/prevención & controlRESUMEN
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 TratamientoRESUMEN
BACKGROUND: Intravenous thrombolysis is a standard treatment of acute ischemic stroke. The efficacy and safety of combining intravenous thrombolysis with argatroban (an anticoagulant agent) or eptifibatide (an antiplatelet agent) are unclear. METHODS: We conducted a phase 3, three-group, adaptive, single-blind, randomized, controlled clinical trial at 57 sites in the United States. Patients with acute ischemic stroke who had received intravenous thrombolysis within 3 hours after symptom onset were assigned to receive intravenous argatroban, eptifibatide, or placebo within 75 minutes after the initiation of thrombolysis. The primary efficacy outcome, the utility-weighted 90-day modified Rankin scale score (range, 0 to 10, with higher scores reflecting better outcomes), was assessed by means of centralized adjudication. The primary safety outcome was symptomatic intracranial hemorrhage within 36 hours after randomization. RESULTS: A total of 514 patients were assigned to receive argatroban (59 patients), eptifibatide (227 patients), or placebo (228 patients). All the patients received intravenous thrombolysis (70% received alteplase, and 30% received tenecteplase), and 225 patients (44%) underwent endovascular thrombectomy. At 90 days, the mean (±SD) utility-weighted modified Rankin scale scores were 5.2±3.7 with argatroban, 6.3±3.2 with eptifibatide, and 6.8±3.0 with placebo. The posterior probability that argatroban was better than placebo was 0.002 (posterior mean difference in utility-weighted modified Rankin scale score, -1.51±0.51) and that eptifibatide was better than placebo was 0.041 (posterior mean difference, -0.50±0.29). The incidence of symptomatic intracranial hemorrhage was similar in the three groups (4% with argatroban, 3% with eptifibatide, and 2% with placebo). Mortality at 90 days was higher in the argatroban group (24%) and the eptifibatide group (12%) than in the placebo group (8%). CONCLUSIONS: In patients with acute ischemic stroke treated with intravenous thrombolysis within 3 hours after symptom onset, adjunctive treatment with intravenous argatroban or eptifibatide did not reduce poststroke disability and was associated with increased mortality. (Funded by the National Institute of Neurological Disorders and Stroke; MOST ClinicalTrials.gov number, NCT03735979.).
Asunto(s)
Eptifibatida , Hemorragias Intracraneales , Accidente Cerebrovascular Isquémico , Péptidos , Ácidos Pipecólicos , Sulfonamidas , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Arginina/administración & dosificación , Arginina/efectos adversos , Arginina/análogos & derivados , Quimioterapia Combinada/efectos adversos , Quimioterapia Combinada/métodos , Eptifibatida/administración & dosificación , Eptifibatida/efectos adversos , Fibrinolíticos/administración & dosificación , Fibrinolíticos/efectos adversos , Infusiones Intravenosas , Hemorragias Intracraneales/inducido químicamente , Hemorragias Intracraneales/epidemiología , Accidente Cerebrovascular Isquémico/mortalidad , Accidente Cerebrovascular Isquémico/terapia , Péptidos/administración & dosificación , Péptidos/efectos adversos , Péptidos/uso terapéutico , Ácidos Pipecólicos/administración & dosificación , Ácidos Pipecólicos/efectos adversos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/efectos adversos , Método Simple Ciego , Sulfonamidas/administración & dosificación , Sulfonamidas/efectos adversos , Terapia Trombolítica/efectos adversos , Terapia Combinada/efectos adversos , Terapia Combinada/métodos , Trombectomía/efectos adversos , Trombectomía/métodos , Resultado del Tratamiento , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Incidencia , AdultoRESUMEN
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
ABSTRACT: Guidelines on antiplatelet recommendation for CYP2C19 intermediate metabolizer (IM) have not come to an agreement. This study aimed to evaluate the clinical benefit of ticagrelor when compared with high-dose clopidogrel in CYP2C19 IM after percutaneous coronary intervention for acute coronary syndromes. Patients were enrolled according to CYP2C19 genotype and individual antiplatelet therapy. Patient characteristics and clinical outcomes were collected through electronic medical record system. The primary outcome was major adverse cardiac and cerebrovascular event (MACCE), namely a composite of death from cardiovascular causes, myocardial infarction, stroke, and stent thrombosis within 12 months. The secondary outcome was Bleeding Academic Research Consortium scale bleeding events within 12 months. The Cox proportional hazards regression model was performed, with inverse probability treatment weighting (IPTW) adjusting for potential confounders. A total of 532 CYP2C19 IM were enrolled in this retrospective single-center study. No statistically significant difference in incidence rate of MACCE was found between patients receiving ticagrelor versus clopidogrel (7.01 vs. 9.52 per 100 patient-years; IPTW-adjusted hazard ratio 0.71; 95% confidence interval: 0.32-1.58; adjusted log-rank P = 0.396), but the incidence rate of Bleeding Academic Research Consortium type 2, 3, or 5 bleeding events was statistically higher in the loss of function-ticagrelor group than in the loss of function-clopidogrel group (13.53 vs. 6.16 per 100 patient-years; IPTW-adjusted hazard ratio: 2.29; 95% confidence interval: 1.10-4.78; adjusted log-rank P = 0.027). Ticagrelor treatment in CYP2C19 IM resulted in a statistically higher risk of bleeding compared with high-dose clopidogrel, whereas a clear association between treatments and MACCE warrants further investigations.
Asunto(s)
Síndrome Coronario Agudo , Clopidogrel , Citocromo P-450 CYP2C19 , Hemorragia , Intervención Coronaria Percutánea , Variantes Farmacogenómicas , Inhibidores de Agregación Plaquetaria , Ticagrelor , Humanos , Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP2C19/metabolismo , Ticagrelor/efectos adversos , Ticagrelor/administración & dosificación , Clopidogrel/efectos adversos , Clopidogrel/administración & dosificación , Síndrome Coronario Agudo/terapia , Síndrome Coronario Agudo/mortalidad , Síndrome Coronario Agudo/diagnóstico , Masculino , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/mortalidad , Femenino , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Resultado del Tratamiento , Hemorragia/inducido químicamente , Factores de Riesgo , Factores de Tiempo , Medición de Riesgo , FenotipoAsunto(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 TiempoRESUMEN
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), Pâ <â .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), Pâ <â .00001]. However, no significant differences were identified in all-cause mortality [RR: 0.96, 95% CI: (0.77, 1.18), Pâ =â .27], myocardial infarction [RR: 0.98, 95% CI: (0.82, 1.18), Pâ =â .86], cardiac death [RR: 0.83, 95% CI: (0.63, 1.10), Pâ =â .20], stroke [RR: 1.08, 95% CI: (0.79, 1.47), Pâ =â .63], cerebrovascular [RR: 1.08, 95% CI: (0.79, 1.47), Pâ =â .63], and stent thrombosis [RR: 1.13, 95% CI: (0.80, 1.57), Pâ =â .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 & controlRESUMEN
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 TratamientoAsunto(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 farmacológicoRESUMEN
The clinical efficacy and safety of antiplatelet agents vary among patients. Consequently, some patients are at increased risk of recurrent ischemic events during treatment. This interindividual variability can be a result of genetic variants in enzymes that play a role in drug metabolism. The field of pharmacogenomics explores the influence of these genetic variants on an individual's drug response. Tailoring antiplatelet treatment based on genetic variants can potentially result in optimized dosing or a change in drug selection. Most evidence supports guiding therapy based on the CYP2C19 allelic variants in patients with an indication for dual antiplatelet therapy. In ticagrelor-treated or prasugrel-treated patients, a genotype-guided de-escalation strategy can reduce bleeding risk, whereas in patients treated with clopidogrel, an escalation strategy may prevent ischemic events. Although the clinical results are promising, few hospitals have implemented these strategies. New results, technological advancements, and growing experience may potentially overcome current barriers for implementation in the future.
Asunto(s)
Genotipo , Inhibidores de Agregación Plaquetaria , Humanos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Citocromo P-450 CYP2C19/genética , Farmacogenética/métodos , Clorhidrato de Prasugrel/uso terapéutico , Clorhidrato de Prasugrel/administración & dosificaciónRESUMEN
In a double-blind, randomized controlled trial, we investigated the effectiveness of adding antiplatelet drugs to up-dosing antihistamines for the treatment of chronic spontaneous urticaria (CSU) in patients with elevated D-dimer levels who had an inadequate response to conventional antihistamine doses. Twenty patients with Urticaria Activity Score over 7 days (UAS7) ≥16 and D-dimer >500 ng/mL were randomized to receive either antiplatelet therapy (cilostazol 150 mg/day + dipyridamole 50 mg/day) with antihistamine (desloratadine 20 mg/day) or antihistamine alone for 4 weeks. The antiplatelet group demonstrated a greater decrease in UAS7 compared to the control group (28.10 to 8.90 vs. 22.90 to 16.40, p < 0.001 vs. p = 0.054). Both groups experienced improved quality of life (DLQI), but the improvement was greater in the antiplatelet group (p = 0.046). D-dimer levels decreased only in the antiplatelet group (1133.67 ng/mL to 581.89 ng/mL, p = 0.013) with no significant change observed in the control group. This suggests that combining dipyridamole and cilostazol with up-dosing antihistamines may be more effective for CSU patients with high D-dimer levels compared to up-dosing antihistamines alone. This could be due to a reduction in platelet activation, as evidenced by the decrease in D-dimer levels observed in the antiplatelet group.
Asunto(s)
Urticaria Crónica , Cilostazol , Dipiridamol , Quimioterapia Combinada , Productos de Degradación de Fibrina-Fibrinógeno , Loratadina , Inhibidores de Agregación Plaquetaria , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Urticaria Crónica/tratamiento farmacológico , Cilostazol/administración & dosificación , Cilostazol/uso terapéutico , Dipiridamol/administración & dosificación , Dipiridamol/uso terapéutico , Método Doble Ciego , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Antagonistas de los Receptores Histamínicos/administración & dosificación , Antagonistas de los Receptores Histamínicos/uso terapéutico , Loratadina/administración & dosificación , Loratadina/uso terapéutico , Loratadina/análogos & derivados , Inhibidores de Agregación Plaquetaria/administración & dosificación , Calidad de Vida , Tetrazoles/administración & dosificación , Tetrazoles/uso terapéutico , Resultado del TratamientoRESUMEN
ABSTRACT: The dual pathway inhibition (DPI) with low-dose rivaroxaban and aspirin in patients with stable atherosclerotic vascular disease reduces the occurrence of cardiovascular events, with no significant increase of intracranial or other critical organ bleedings. Our observational study aimed to describe the clinical performance, adherence, and persistence of DPI therapy among a real-world setting of patients with an established diagnosis of coronary artery (CAD) and/or peripheral artery disease (PAD). We prospectively included all consecutive patients with an established diagnosis of CAD and/or PAD treated with aspirin (ASA) 100 mg once daily and rivaroxaban 2.5 mg twice daily. Clinical evaluation was performed at baseline, before starting treatment, at 1 month, and every 6 months after the study drug administration. A total of 202 consecutive patients (mean age 66 ± 10 years; male 80%) eligible to DPI therapy were included. During a mean follow-up of 664 ± 177 days, the incidence rate of major bleedings and of major adverse cardiovascular events was 0.8 and 1.1 per 100 patients/year, respectively. The adherence to pharmacological treatment was 99%. Additionally, 13.4% of patients suspended the DPI therapy during the follow-up. Minor bleedings resulted the most common cause of both temporary and permanent DPI therapy discontinuation. This observational study supports the safety of DPI with low-dose rivaroxaban and aspirin among patients with CAD and PAD in a real-world setting, showing high persistence and maximum adherence to medical treatment.
Asunto(s)
Aspirina , Enfermedad de la Arteria Coronaria , Inhibidores del Factor Xa , Hemorragia , Cumplimiento de la Medicación , Enfermedad Arterial Periférica , Inhibidores de Agregación Plaquetaria , Rivaroxabán , Humanos , Rivaroxabán/efectos adversos , Rivaroxabán/administración & dosificación , Aspirina/efectos adversos , Aspirina/administración & dosificación , Aspirina/uso terapéutico , Masculino , Anciano , Femenino , Inhibidores del Factor Xa/efectos adversos , Inhibidores del Factor Xa/administración & dosificación , Enfermedad Arterial Periférica/tratamiento farmacológico , Enfermedad Arterial Periférica/diagnóstico , Enfermedad Arterial Periférica/fisiopatología , Enfermedad Arterial Periférica/epidemiología , Estudios Prospectivos , Persona de Mediana Edad , Hemorragia/inducido químicamente , Resultado del Tratamiento , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/uso terapéutico , Factores de Tiempo , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Enfermedad de la Arteria Coronaria/diagnóstico , Factores de RiesgoRESUMEN
SOURCE CITATION: Park DY, Hu JR, Jamil Y, et al. Shorter dual antiplatelet therapy for older adults after percutaneous coronary intervention: a systematic review and network meta-analysis. JAMA Netw Open. 2024;7:e244000. 38546647.
Asunto(s)
Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria , Humanos , Anciano , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Terapia Antiplaquetaria Doble , Hemorragia/inducido químicamente , Esquema de MedicaciónRESUMEN
SOURCE CITATION: Ge Z, Kan J, Gao X, et al; ULTIMATE-DAPT investigators. Ticagrelor alone versus ticagrelor plus aspirin from month 1 to month 12 after percutaneous coronary intervention in patients with acute coronary syndromes (ULTIMATE-DAPT): a randomised, placebo-controlled, double-blind clinical trial. Lancet. 2024;403:1866-1878. 38599220.