Timing of P2Y12 Inhibitor Administration in Patients With STEMI Undergoing Primary PCI.

BACKGROUND: The optimal timing of P2Y12 inhibitor administration in patients with ST-segment elevation myocardial infarction (STEMI) has not been completely elucidating. OBJECTIVES: This analysis from a prospective multicenter registry sought to assess the safety and effectiveness of P2Y12 inhibitor pretreatment in patients transferred for primary percutaneous coronary intervention (PCI) within a regional STEMI network. METHODS: Pretreatment was defined as P2Y12 inhibitor administration before coronary angiography. Endpoints were major adverse cardiac events (MACE), major bleeding, and net adverse clinical events, a composite of MACE or major bleeding, within 30 days of index admission. Association of P2Y12 inhibitor pretreatment with outcomes was modeled using doubly robust weighted estimators based on propensity score analysis. RESULTS: Of 1,624 patients included, 1,033 received P2Y12 inhibitors before angiography and 591 in the catheterization laboratory (cath lab). The non-pretreated cohort more often had history of coronary artery disease and were more likely to receive antiplatelet therapy before the index admission. After adjustment for confounding and dependent censoring, pretreatment with P2Y12 inhibitors predicted lower risk of MACE (adjusted HR: 0.53; 95% CI: 0.37-0.76), without increasing bleeding risk (adjusted HR: 0.62; 95% CI: 0.36-1.05), resulting in superior net clinical benefit (adjusted HR: 0.47; 95% CI: 0.26-0.86) compared with in-cath lab administration of P2Y12 inhibitors. There was a significant treatment-by-time interaction for MACE risk, whereby the observed benefits of pretreatment only became apparent when time between P2Y12 inhibitor administration and PCI was longer than 80 minutes. CONCLUSIONS: In contemporary patients with STEMI transferred for primary PCI, pretreatment with P2Y12 inhibitors was associated with a significant time-dependent reduction of 30-day MACE without increasing bleeding risk.

Falta de adherencia a ticagrelor frente a clopidogrel y riesgo de eventos en pacientes con SCA. Resultados del registro CREA-ARIAM / Nonadherence to ticagrelor versus clopidogrel and clinical outcomes in patients with ACS. Results from the CREA-ARIAM registry

Introduction and objectives Prior studies have not determined whether the effect of dual antiplatelet therapy (DAPT) cessation on the subsequent risk of major adverse cardiac events (MACE) varies by the choice of P2Y12-inhibitor after acute coronary syndrome (ACS). Methods We performed a prespecified subanalysis of a multicenter, prospective registry of ACS patients discharged on ticagrelor or clopidogrel between 2015 and2019. Nonadherence to DAPT was categorized as physician-guided discontinuation and disruption due to adverse effects, nonadherence, or bleeding. The association between DAPT cessation and 1-year MACE was analyzed using multivariate time-updated Cox models with inverse probability of censoring weighted estimators. Results Out of 2180 patients, 174 (8.3%) prematurely discontinued DAPT (physician-guided, n=126; disruption, n=48). Nonadherent patients were older and had more comorbidities than those on DAPT. Compared with physician-guided discontinuation, disruption occurred earlier after discharge and was more frequent with ticagrelor than with clopidogrel. In time-varying analysis, DAPT cessation was associated with an increased risk of MACE (adjusted HR, 1.32, 95%CI, 1.10-1.76), largely driven by disruption (adjusted HR, 1.47, 95%CI, 1.22-1.73). There was an exponential increase in MACE risk after DAPT cessation within 90 days after ACS, especially after disruption of ticagrelor compared with clopidogrel (Pinteraction<.001). After adjustment for DAPT duration, this interaction was not statistically significant on the additive scale (relative excess risk due to interaction 0.12, 95%CI,−0.99-1.24). Conclusions In this all-comers registry, 1 in 12 patients prematurely discontinued DAPT within 1 year after ACS. Compared with physician-recommended discontinuation, disruption resulted in a significantly higher risk of MACE. After adjustment for DAPT duration, this association was not moderated by the choice of P2Y12-inhibitor (AU)

Introducción y objetivos Una baja adherencia al tratamiento antiagregante plaquetario doble (TAPD) condiciona peor pronóstico tras un síndrome coronario agudo (SCA). Se analizó si el riesgo de eventos adversos cardiovasculares mayores (MACE) tras la interrupción prematura del TAPD varía según el inhibidor del P2Y12. Métodos Análisis preespecificado de pacientes con SCA tratados con ticagrelor o clopidogrel entre 2015 y 2019 dentro de un registro prospectivo multicéntrico. Se categorizó la suspensión prematura como indicada por el médico o como interrupción por hemorragia, efectos secundarios o incumplimiento del paciente. La asociación entre la suspensión del TAPD y los MACE se analizó mediante modelos multivariantes de Cox dependientes del tiempo, con estimadores robustos ponderados por probabilidad inversa de censura. Resultados De 2.180 pacientes, 174 (8,3%) suspendieron el TAPD precozmente (126 por indicación médica y 48 por disrupción). Los pacientes incumplidores tenían más edad y más comorbilidad que los adherentes. Frente a la suspensión indicada por el médico, la disrupción del TAPD fue más precoz y frecuente con el ticagrelor que con el clopidogrel. La suspensión del TAPD condicionó mayor riesgo de MACE (HRajustada=1,32; IC95%, 1,10-1,76), principalmente en caso de la disrupción (HRajustada=1,47; IC95%, 1,22-1,73). Este riesgo aumentó exponencialmente en los 90 días posteriores al SCA y fue más evidente con ticagrelor (pinteracción<0,001). Tras considerar la duración del TAPD, esta interacción no resultó significativa en la escala aditiva (exceso de riesgo debido a interacción=0,12; IC95%, –0,99 a 1,24)(AU)

Nonadherence to ticagrelor versus clopidogrel and clinical outcomes in patients with ACS. Results from the CREA-ARIAM registry.

INTRODUCTION AND OBJECTIVES: Prior studies have not determined whether the effect of dual antiplatelet therapy (DAPT) cessation on the subsequent risk of major adverse cardiac events (MACE) varies by the choice of P2Y12-inhibitor after acute coronary syndrome (ACS). METHODS: We performed a prespecified subanalysis of a multicenter, prospective registry of ACS patients discharged on ticagrelor or clopidogrel between 2015 and2019. Nonadherence to DAPT was categorized as physician-guided discontinuation and disruption due to adverse effects, nonadherence, or bleeding. The association between DAPT cessation and 1-year MACE was analyzed using multivariate time-updated Cox models with inverse probability of censoring weighted estimators. RESULTS: Out of 2180 patients, 174 (8.3%) prematurely discontinued DAPT (physician-guided, n=126; disruption, n=48). Nonadherent patients were older and had more comorbidities than those on DAPT. Compared with physician-guided discontinuation, disruption occurred earlier after discharge and was more frequent with ticagrelor than with clopidogrel. In time-varying analysis, DAPT cessation was associated with an increased risk of MACE (adjusted HR, 1.32, 95%CI, 1.10-1.76), largely driven by disruption (adjusted HR, 1.47, 95%CI, 1.22-1.73). There was an exponential increase in MACE risk after DAPT cessation within 90 days after ACS, especially after disruption of ticagrelor compared with clopidogrel (Pinteraction<.001). After adjustment for DAPT duration, this interaction was not statistically significant on the additive scale (relative excess risk due to interaction 0.12, 95%CI,-0.99-1.24). CONCLUSIONS: In this all-comers registry, 1 in 12 patients prematurely discontinued DAPT within 1 year after ACS. Compared with physician-recommended discontinuation, disruption resulted in a significantly higher risk of MACE. After adjustment for DAPT duration, this association was not moderated by the choice of P2Y12-inhibitor. Clinical trial registered at ClinicalTrials.gov (Identifier: NCT02500290).

Comparative Safety and Effectiveness of Ticagrelor versus Clopidogrel in Patients With Acute Coronary Syndrome: An On-Treatment Analysis From a Multicenter Registry.

Background: The net clinical benefit of ticagrelor over clopidogrel in acute coronary syndrome (ACS) has recently been questioned by observational studies which did not account for time-dependent confounders. We aimed to assess the comparative safety and effectiveness of ticagrelor vs. clopidogrel accounting for non-adherence in a real-life setting. Methods: This is a prospective, multicenter cohort study of patients with ACS discharged on ticagrelor or clopidogrel between 2015 and 2019. Major exclusions were previous intracranial bleeding, and the use of prasugrel or oral anticoagulation. Association of P2Y12 inhibitor therapy with 1-year risk of Bleeding Academic Research Consortium Type 3 or 5 bleeding; major adverse cardiac events (MACEs), a composite endpoint of all-cause death, nonfatal myocardial infarction (MI), nonfatal stroke, or urgent target lesion revascularization; definite/probable stent thrombosis; vascular death; and net adverse clinical event (a composite endpoint of major bleeding and MACE) were analyzed according to the "on-treatment" principle, using fully adjusted Cox and Fine-Gray regression models with doubly robust inverse probability of censoring weighted estimators. Results: Among 2,070 patients (mean age 63 years, 27% women, 62.5% ST-elevation MI), 1,035 were discharged on ticagrelor and clopidogrel, respectively. Ticagrelor-treated patients were younger and had few comorbidities, but high rates of medication non-compliance, compared with clopidogrel users. After comprehensive multivariate adjustments, ticagrelor did not increase the risk of major bleeding compared with clopidogrel [subhazard ratio, 1.40; 95% confidence interval (CI), 0.96-2.05], while proved superior in reducing MACE (hazard ratio 0.62; 95% CI, 0.43-0.90), vascular death (subhazard ratio, 0.71; 95% CI, 0.52-0.97) and definite/probable stent thrombosis (subhazard ratio, 0.54; 95% CI, 0.30-0.79); thereby resulting in a favorable net clinical benefit (hazard ratio 0.78; 95% CI, 0.60-0.98) compared with clopidogrel. Results from sensitivity analyses were consistent with those from the primary analysis, whereas those from the intention-to-treat (ITT) analysis went in the opposite direction. Conclusion: Among all-comers with ACS, ticagrelor did not significantly increase the risk of major bleeding, while resulting in a net clinical benefit compared with clopidogrel. Further research is warranted to confirm these findings in high bleeding risk populations. CREA-ARIAM Andalucía: (ClinicalTrials.gov Identifier: NCT02500290); Current pre-specified analysis (ClinicalTrials.gov Identifier: NCT04630288).

Fondaparinux versus enoxaparin in the contemporary management of non-ST-elevation acute coronary syndromes. Insights from a multicenter registry.

BACKGROUND: Fondaparinux is thought to have the most favorable risk-benefit profile among all anticoagulants in non-ST-elevation acute coronary syndrome (NSTE-ACS). However, conflicting findings exist whether this holds true in current clinical practice. We aimed to assess the net clinical benefit of fondaparinux versus enoxaparin in the contemporary management of NSTE-ACS. METHODS: Analysis of prospective multicenter registry data of NSTE-ACS patients who received fondaparinux or enoxaparin from February 2015, through December 2017. Survival models within a competing risks framework including site-specific random effects, were used to assess the composite of clinically relevant bleedings and major adverse cardiovascular events at 30 days. RESULTS: Of 2094 patients, 1724 (82%) received enoxaparin and 370 (18%) fondaparinux. Both groups were comparable except for a lower prevalence of diabetes and renal impairment, and greater use of transradial approach in the fondaparinux group. Multivariate analysis revealed a net clinical benefit in favour of fondaparinux versus enoxaparin (Subhazard Ratio [SHR] 0.59; 95%CI 0.37-0.92), mainly driven by a reduction in bleeding (SHR 0.57; 95%CI 0.37-0.89). Exploratory analysis suggested greater reductions in bleeding with fondaparinux among patients undergoing transradial approach, revealing a significant interaction between treatment and vascular access on the multiplicative scale (Pinteraction = 0.0056), but not on an additive scale (P = 0.457). Propensity-score-matching analysis yielded similar results. CONCLUSIONS: In contemporary management of NSTE-ACS, fondaparinux seems to provide a favorable net clinical benefit compared with enoxaparin, primarily driven by a bleeding reduction. Effect modification on the safety profile of fondaparinux by the vascular access approach warrants further investigation.

Síndrome coronario agudo en la mujer. Diferencias de género / Acute coronary syndrome in women. Gender differences

Fundamento y objetivo: Analizar si hay indicios de diferencias por género en el diagnóstico, tratamiento y pronóstico de los pacientes ingresados con síndrome coronario agudo (SCA). Pacientes y método: Estudio prospectivo de una cohorte de 396 pacientes que ingresaron a lo largo de un período de 18 meses en una unidad coronaria con el diagnóstico de SCA. Se dividió a los pacientes en dos grupos en función del género (294 varones y 102 mujeres). Se analizaron las medidas diagnósticas, el tratamiento hospitalario, la revascularización coronaria (ICP), la aparición de insuficiencia cardíaca (IC) y la mortalidad intrahospitalaria y al año. Resultados: La edad media (±DE) de las mujeres fue mayor (70,9±11,9 frente al 64,4±12,0 años; p<0,001) y presentaron más comorbilidades, tales como hipertensión (70,5% frente al 53,7%; p<0,01), diabetes (51,0% frente al 33,3%; p<0,01) e IC previa (20,5% frente al 9,1%; p<0,01) que los varones, mientras que estos presentaron mayor frecuencia de tabaquismo (54,4% frente al 13,7%; p<0,001). Las mujeres presentaron mayor incidencia de shock cardiogénico al ingreso. No hubo diferencias entre ambos sexos en el tratamiento trombolítico, ni en el patrón de acceso a la angiografía coronaria, pero los varones presentaron mayor frecuencia de ICP con éxito (50,8% frente al 34,6%; p<0,01). Las mujeres presentaron con más frecuencia IC intrahospitalaria (32,6% frente al 25,9%; p<0,05) y muerte intrahospitalaria (17,6% frente al 4,7%; p<0,001). En el análisis multivariante, la insuficiencia cardíaca al ingreso (odds ratio [OR]: 8,98; intervalo de confianza del 95% [IC 95%]: 3,29-24,47), la mayor edad (OR: 1,07; IC 95%: 1,01-1,13) y el género femenino (OR: 3,14; IC 95%: 1,27-7,74) fueron predictores independientes de mortalidad hospitalaria.Conclusiones: En nuestro estudio, el género femenino fue un predictor independiente de mortalidad hospitalaria en pacientes con SCA (AU)

Background and objective: Our aims was to investigate possible gender differences in the diagnostic assessment, treatment and prognosis of patients admitted with acute coronary syndrome (ACS).Patients and methods: Prospective study of a cohort of 396 patients consecutively admitted to the coronary unit in the period of 18 months with the diagnoses of ACS. We divided the sample into two groups based on gender: 294 men and 102 women. We analysed the diagnostic assessment, hospital treatment, coronary revascularization (ICP), appearance of heart failure (HF) and in-hospital and 1-year mortality. We analyzed predictors of mortality in a multivariate model. Results:Women were older (70.9±11.9 versus 64.4±12.0; P<.001) and had more comorbidities such as hypertension (70.5% versus 53.7%; P=.003), diabetes (51.0% versus 33.3%; P<.01) and HF (20.5% versus 9.1%; P<.01) than men, while men had greater frequency of smoking (54.42% versus 13.73%; P<.001). Women had higher incidence of cardiogenic shock on admission. There were no differences in thrombolysis and women did not have a different pattern of access to coronary angiography, but men had greater frequency of ICP (50.8% versus 34.6%; P<.01). Women were more likely to develop a higher in-hospital HF (32.6% versus 25.9%; P<.05) and in-hospital mortality (17.6% versus 4.7%; P<.001). In the multivariate analyses, HF on admission OR 8.98 (3.29-24.47), older age OR 1.07 (1.01-1.13) and female gender OR 3.14 (1.27-7.74), were independent predictors of in-hospital mortality.Conclusions: In our study, female gender was an independent predictor of in-hospital mortality in patients with ACS (AU)

[Acute coronary syndrome in women. Gender differences]. / Síndrome coronario agudo en la mujer. Diferencias de género.

BACKGROUND AND OBJECTIVE: Our aims was to investigate possible gender differences in the diagnostic assessment, treatment and prognosis of patients admitted with acute coronary syndrome (ACS). PATIENTS AND METHODS: Prospective study of a cohort of 396 patients consecutively admitted to the coronary unit in the period of 18 months with the diagnoses of ACS. We divided the sample into two groups based on gender: 294 men and 102 women. We analysed the diagnostic assessment, hospital treatment, coronary revascularization (ICP), appearance of heart failure (HF) and in-hospital and 1-year mortality. We analyzed predictors of mortality in a multivariate model. RESULTS: Women were older (70.9±11.9 versus 64.4±12.0; P<.001) and had more comorbidities such as hypertension (70.5% versus 53.7%; P=.003), diabetes (51.0% versus 33.3%; P<.01) and HF (20.5% versus 9.1%; P<.01) than men, while men had greater frequency of smoking (54.42% versus 13.73%; P<.001). Women had higher incidence of cardiogenic shock on admission. There were no differences in thrombolysis and women did not have a different pattern of access to coronary angiography, but men had greater frequency of ICP (50.8% versus 34.6%; P<.01). Women were more likely to develop a higher in-hospital HF (32.6% versus 25.9%; P<.05) and in-hospital mortality (17.6% versus 4.7%; P<.001). In the multivariate analyses, HF on admission OR 8.98 (3.29-24.47), older age OR 1.07 (1.01-1.13) and female gender OR 3.14 (1.27-7.74), were independent predictors of in-hospital mortality. CONCLUSIONS: In our study, female gender was an independent predictor of in-hospital mortality in patients with ACS.

[Factors related to refuse antiretroviral therapy in prison]. / Factores relacionados con rehusar el tratamiento antirretroviral en prisión.

INTRODUCTION: Despite the benefits of highly-active antiretroviral therapy (HAART) on morbidity and mortality, some seropositive patients refuse to accept this treatment. Prisons provide easier access to this population. OBJECTIVE: To determine the psychosocial characteristics of prisoners who refuse HAART. METHODS: We performed a cross-sectional study in 580 seropositive prisoners in 3 hospitals in Andalusia (Spain). The dependent variable was being under treatment or refusal to be so. The independent variables were sociodemographic and psychosocial factors related to the prison environment and clinical factors related to health status and drug addiction. A logistic regression analysis was performed to determine which factors were related with refusal to accept HAART. RESULTS: HAART was recommended to 73.1% of seropositive prisoners. This treatment was refused by 23.1% of these prisoners and was accepted by 76.9%. The factors related to refusal to accept HAART were high viral load, worse self-perceived health status, a greater number of stays in prison, and being visited by persons other than relatives. CONCLUSIONS: There is a group of prisoners with specific characteristics that refuse HAART. Specific interventions should be performed in these prisoners to make them aware of the effects of their decision on the course of their disease.

Factores relacionados con rehusar el tratamiento antirretroviral en prisión / Factors related to refuse antiretroviral therapy in prison

Introducción: A pesar de los beneficios sobre la morbilidad y la mortalidad que tiene el tratamiento antirretroviral de gran actividad, hay pacientes seropositivos que rehúsan tomarlo. Las prisiones nos permiten acceder con más facilidad a esta población. Objetivo: Determinar las características psicosociales de los reclusos que rehúsan el tratamiento antirretroviral. Metodología: Estudio transversal realizado a 580 reclusos seropositivos de 3 cárceles andaluzas. Como variable dependiente se estableció estar en tratamiento o rehusarlo. Las variables independientes fueron: sociodemográficas, psicosociales, relacionadas con el medio penitenciario, clínicas, y relacionadas con el estado de salud y con las drogodependencias. Se realizó un análisis de regresión logística para determinar qué factores se relacionaban con rehusar el tratamiento antirretroviral. Resultados: Al 73,1% de los reclusos seropositivos se les recomendaba el tratamiento con antirretrovirales. De éstos, el 23,1% rechazaba tomarlo, mientras el 76,9% lo tomaba. Los factores relacionados con los reclusos que rehusaban el tratamiento antirretroviral fueron una carga viral elevada, una peor salud autopercibida, un mayor número de entradas en la cárcel y ser visitados por personas diferentes a los familiares. Conclusiones: Hay un grupo de reclusos con características propias que rechazan el tratamiento antirretroviral, sobre el que deben realizarse intervenciones específicas encaminadas a que conozcan las consecuencias de su decisión sobre la evolución de su enfermedad (AU)

Introduction: Despite the benefits of highly-active antiretroviral therapy (HAART) on morbidity and mortality, some seropositive patients refuse to accept this treatment. Prisons provide easier access to this population. Objective: To determine the psychosocial characteristics of prisoners who refuse HAART. Methods: We performed a cross-sectional study in 580 seropositive prisoners in 3 hospitals in Andalusia (Spain). The dependent variable was being under treatment or refusal to be so. The independent variables were sociodemographic and psychosocial factors related to the prison environment and clinical factors related to health status and drug addiction. A logistic regression analysis was performed to determine which factors were related with refusal to accept HAART. Results: HAART was recommended to 73.1% of seropositive prisoners. This treatment was refused by 23.1% of these prisoners and was accepted by 76.9%. The factors related to refusal to accept HAART were high viral load, worse self-perceived health status, a greater number of stays in prison, and being visited by persons other than relatives. Conclusions: There is a group of prisoners with specific characteristics that refuse HAART. Specific interventions should be performed in these prisoners to make them aware of the effects of their decision on the course of their disease (AU)