RESUMO
In patients with stable atherosclerotic cardiovascular disease, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9is) have shown a 50% to 60% reduction in low-density lipoprotein cholesterol (LDL-C) from baseline when added to high-intensity statin therapy. However, less is known about the impact of PCSK9is in the setting of an acute coronary syndrome (ACS). Therefore, we performed a systematic review and meta-analysis comparing PCSK9is with placebo in the setting of ACS added to guideline-directed high-intensity or maximally tolerated statin therapy. We included randomized controlled trials with initiation of a PCSK9i or placebo within 1 week of presentation or percutaneous coronary intervention for ACS. PubMed, EMBASE, and Cochrane Central were searched. This study followed the Cochrane and Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) recommendations. A total of 6 randomized controlled trials were included, with a total of 996 patients, of whom 503 (50.5%) received PCSK9is. The mean follow-up ranged from 4 to 52 weeks. The LDL-C (mean difference [MD] -44.0 mg/100 ml, CI -54.3 to -33.8, p <0.001) and lipoprotein (a) levels (MD -24.0 nmol/L, confidence interval [CI] -43.0 to -4.9, pâ¯=â¯0.01) were significantly lower at follow-up with PCSK9is. Similarly, the total cholesterol (MD -49.2 mg/100 ml, CI -59.0 to -39.3), triglycerides (MD -19.0 mg/100 ml, CI -29.9 to -8.2), and apolipoprotein B (MD -33.3 mg/100 ml, CI -44.4 to -22.1) were significantly reduced with PCSK9is. In conclusion, in patients with ACS, early initiation of PCSK9i added to statin significantly reduces LDL-C and lipoprotein (a) levels compared with placebo. Whether the differences in these atherogenic lipoproteins translate into a reduction in clinical end points is yet to be determined.
Assuntos
Síndrome Coronariana Aguda , Anticolesterolemiantes , Aterosclerose , Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , LDL-Colesterol , Pró-Proteína Convertase 9 , Inibidores de PCSK9 , Síndrome Coronariana Aguda/tratamento farmacológico , Aterosclerose/tratamento farmacológico , Lipoproteína(a) , Anticolesterolemiantes/uso terapêuticoRESUMO
Anticoagulant treatment, together with antiplatelet therapy, plays an important role in the treatment of acute coronary syndromes. Its use is associated with a reduction in new ischemic events, stent thrombosis, and lower mortality. However, in clinical practice there is great heterogeneity in its use, leading to suboptimal results in treatment. This paper conducts a narrative review on the use of parenteral anticoagulants in patients with acute coronary syndromes, depending on the clinical scenario, as well as the revascularization strategy used and the bleeding risk. The different anticoagulant schemes available in acute coronary syndromes with and without segment ST elevation are addressed, based on the updated evidence. Finally, evidence-based strategies for risk stratification for bleeding and therapeutic management are developed.
El tratamiento anticoagulante, en conjunto con la anti agregación, cumple un rol de suma importancia en el tratamiento de los síndromes coronarios agudos. Su uso está asociado a reducción de nuevos eventos isquémicos, trombosis del stent e incluso menor mortalidad. No obstante, en la práctica clínica existe una gran heterogeneidad en su utilización, llevando a resultados subóptimos en el tratamiento. Este trabajo ofrece una revisión narrativa sobre el uso de anticoagulantes parenterales en pacientes con síndromes coronarios agudos, dependiendo del escenario clínico, así como también de la estrategia de revascularización implementada y el riesgo hemorrágico. Se abordan los diferentes esquemas anticoagulantes disponibles en síndromes coronarios agudos con y sin elevación del segmento ST, basados en la evidencia actualizada hasta la fecha. Finalmente, se desarrollan herramientas para la estratificación del riesgo de sangrado y su manejo terapéutico.
Assuntos
Síndrome Coronariana Aguda , Anticoagulantes , Humanos , Síndrome Coronariana Aguda/tratamento farmacológico , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Hemorragia/induzido quimicamente , Hemorragia/prevenção & controleRESUMO
The appropriate time for the administration of P2Y12 inhibitors in patients with non-ST elevation acute coronary syndrome has been the subject of debate for two decades. The current recommendations of the European guidelines suggest administering acetylsalicylic acid and waiting for the coronary angiography and once the anatomy is known, adding a P2Y12 inhibitor only in those cases in which an early interventional strategy is scheduled. However, in the real world, the strategy to perform pretreatment or not is more complex. There is uncertainty regarding whether the patient can access a coronary angiography within 24 hours. In this scenario, pretreatment upon admission of intermediate or high-risk patients could be an option if it is not studied with catheterization within 2 to 4 hours of admission, previously analyzing the patient's ischemic and bleeding risk. Large-scale studies comparing these two options are still lacking.
El momento adecuado para la administración de los inhibidores P2Y12 en pacientes con síndrome coronario agudo sin elevación del segmento ST es tema de debate desde hace dos décadas. Las recomendaciones actuales de las guías europeas sugieren administrar ácido acetilsalicílico y aguardar el momento de la cinecoronariografía, y una vez conocida la anatomía agregar un inhibidor P2Y12 solo en aquellos casos en que se programe una estrategia intervencionista precoz. Sin embargo, en el mundo real la estrategia de realizar o no pretratamiento es más compleja. Existe la incertidumbre respecto a que el paciente pueda acceder o no a una cinecoronariografía dentro de las 24 horas. En este escenario, el pretratamiento al ingreso de un paciente de riesgo intermedio o alto podría ser una opción si no va a ser estudiado con cateterismo dentro de las 2 a 4 horas del ingreso, analizando previamente el riesgo isquémico y de sangrado del paciente. Aún faltan estudios a gran escala que comparen estas dos opciones.
Assuntos
Síndrome Coronariana Aguda , Intervenção Coronária Percutânea , Humanos , Aspirina , Síndrome Coronariana Aguda/tratamento farmacológico , Angiografia Coronária , Inibidores da Agregação Plaquetária/uso terapêutico , Resultado do TratamentoRESUMO
Dual antiplatelet therapy (DAPT) is currently the standard of care after percutaneous coronary intervention (PCI). Recent studies suggest that reducing DAPT to 1-3 months followed by an aspirin-free single antiplatelet therapy (SAPT) strategy with a potent P2Y12 inhibitor is safe and associated with less bleeding. However, to date, no randomised trial has tested the impact of initiating SAPT immediately after PCI, particularly in patients with acute coronary syndromes (ACS). NEOMINDSET is a multicentre, randomised, open-label trial with a blinded outcome assessment designed to compare SAPT versus DAPT in 3,400 ACS patients undergoing PCI with the latest-generation drug-eluting stents (DES). After successful PCI and up to 4 days following hospital admission, patients are randomised to receive SAPT with a potent P2Y12 inhibitor (ticagrelor or prasugrel) or DAPT (aspirin plus a potent P2Y12 inhibitor) for 12 months. Aspirin is discontinued immediately after randomisation in the SAPT group. The choice between ticagrelor and prasugrel is at the investigator's discretion. The primary hypothesis is that SAPT will be non-inferior to DAPT with respect to the composite endpoint of all-cause mortality, stroke, myocardial infarction or urgent target vessel revascularisation, but superior to DAPT on rates of bleeding defined by Bleeding Academic Research Consortium 2, 3 or 5 criteria. NEOMINDSET is the first study that is specifically designed to test SAPT versus DAPT immediately following PCI with DES in ACS patients. This trial will provide important insights on the efficacy and safety of withdrawing aspirin in the early phase of ACS. (ClinicalTrials.gov: NCT04360720).
Assuntos
Síndrome Coronariana Aguda , Stents Farmacológicos , Intervenção Coronária Percutânea , Humanos , Inibidores da Agregação Plaquetária/uso terapêutico , Ticagrelor/uso terapêutico , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/cirurgia , Cloridrato de Prasugrel/uso terapêutico , Intervenção Coronária Percutânea/efeitos adversos , Quimioterapia Combinada , Aspirina/uso terapêutico , Hemorragia/induzido quimicamente , Resultado do TratamentoRESUMO
INTRODUCTION: The optimal anti-thrombotic therapy to prevent recurrent ischemic events in patients with acute coronary syndrome and coronary artery ectasia (CAE) remains unclear. AIM: To assess the efficacy and safety of antiplatelet plus anticoagulant therapy versus dual antiplatelet therapy in patients with acute coronary syndromes and coronary artery ectasia. METHODS: OVER-TIME is an investigator initiated, exploratory, open label, single center, randomized clinical trial comparing dual antiplatelet therapy (acetyl-salicylic acid plus a P2Y12 inhibitor) with the combination of an antiplatelet monotherapy (a P2Y12 inhibitor) plus a low dose anticoagulant (rivaroxaban, 15mg oral dose) for the prevention of recurrent ischemic events among patients with CAE. We aim to enroll approximately 60 patients with CAE and acute coronary syndromes. After recruitment, patients are randomized to (a) standard of care (dual antiplatelet regimen) or (b) the combination of antiplatelet monotherapy and low dose anticoagulant. Patients will be followed for at least 12 months. The OVER-TIME study aims to assess the efficacy of the regimen in prevention of major cardiovascular events and its security in bleeding events in acute coronary syndromes among patients with CAE. Expected results and conclusions: OVER-TIME is the first randomized controlled trial to assess different antithrombotic strategies in patients with CAE and acute coronary syndrome, and its results will offer preliminary data for the prevention of major cardiovascular events and bleeding events in this group of patients. TRIAL REGISTRATION NUMBER: NCT05233124 (ClinicalTrials.gov), date of registration: February 10, 2022.
Assuntos
Síndrome Coronariana Aguda , Intervenção Coronária Percutânea , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/tratamento farmacológico , Anticoagulantes/efeitos adversos , Vasos Coronários , Dilatação Patológica/induzido quimicamente , Dilatação Patológica/tratamento farmacológico , Quimioterapia Combinada , Fibrinolíticos/efeitos adversos , Hemorragia/induzido quimicamente , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação Plaquetária/efeitos adversos , Rivaroxabana , Ácido Salicílico/uso terapêutico , Resultado do TratamentoRESUMO
Importance: Data are limited regarding the risk of cerebrovascular ischemic events and major bleeding in patients with atrial fibrillation (AF) and recent acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI). Objective: Determine the efficacy and safety of apixaban or vitamin K antagonists (VKA) and aspirin or placebo according to prior stroke, transient ischemic attack (TIA), or thromboembolism (TE). Design, Setting, and Participants: In this prospective, multicenter, 2-by-2 factorial, randomized clinical trial, post hoc parallel analyses were performed to compare randomized treatment regimens according to presence or absence of prior stroke/TIA/TE using Cox proportional hazards models. Patients with AF, recent ACS or PCI, and planned use of P2Y12 inhibitors for 6 months or longer were included; 33 patients with missing data about prior stroke/TIA/TE were excluded. Interventions: Apixaban (5 mg or 2.5 mg twice daily) or VKA and aspirin or placebo. Main Outcomes and Measures: Major or clinically relevant nonmajor (CRNM) bleeding. Results: Of 4581 patients included, 633 (13.8%) had prior stroke/TIA/TE. Patients with vs without prior stroke/TIA/TE were older; had higher CHA2DS2-VASC and HAS-BLED scores; and more frequently had prior bleeding, heart failure, diabetes, and prior oral anticoagulant use. Apixaban was associated with lower rates of major or CRNM bleeding and death or hospitalization than VKA in patients with (hazard ratio [HR], 0.69; 95% CI, 0.46-1.03) and without (HR, 0.68; 95% CI, 0.57-0.82) prior stroke/TIA/TE. Patients without prior stroke/TIA/TE receiving aspirin vs placebo had higher rates of bleeding; this difference appeared less substantial among patients with prior stroke/TIA/TE (P = .01 for interaction). Aspirin was associated with numerically lower rates of death or ischemic events than placebo in patients with (HR, 0.71; 95% CI, 0.42-1.20) and without (HR, 0.93; 95% CI, 0.72-1.21) prior stroke/TIA/TE (not statistically significant). Conclusions and Relevance: The safety and efficacy of apixaban compared with VKA was consistent with the AUGUSTUS findings, irrespective of prior stroke/TIA/TE. Aspirin increased major or CRNM bleeding, particularly in patients without prior stroke/TIA/TE. Although aspirin may have some benefit in patients with prior stroke, our findings support the use of apixaban and a P2Y12 inhibitor without aspirin for the majority of patients with AF and ACS and/or PCI, regardless of prior stroke/TIA/TE status. Trial Registration: ClinicalTrials.gov Identifier: NCT02415400.
Assuntos
Síndrome Coronariana Aguda , Fibrilação Atrial , Ataque Isquêmico Transitório , Intervenção Coronária Percutânea , Acidente Vascular Cerebral , Tromboembolia , Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/cirurgia , Anticoagulantes , Aspirina , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Fibrinolíticos/uso terapêutico , Hemorragia/induzido quimicamente , Hemorragia/complicações , Hemorragia/epidemiologia , Humanos , Estudos Prospectivos , Pirazóis , Piridonas , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Tromboembolia/induzido quimicamente , Varfarina/efeitos adversosAssuntos
Humanos , Masculino , Feminino , Prescrições de Medicamentos , Trombose/complicações , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/terapia , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Inibidores da Agregação Plaquetária/administração & dosagem , Aspirina/administração & dosagem , Isquemia Miocárdica/terapia , Analgesia/métodos , Anticoagulantes/administração & dosagem , Hipolipemiantes/uso terapêuticoRESUMO
Ticagrelor is anantiplatelet agent which acts through reversible binding to the P2Y12 adenosine-diphosphate receptors. In acute coronary syndromes it has been shown to reduce the risk of major cardiovascular events such as myocardial infarction, stroke and death. Although some hemorrhagic, kidney, liver and respiratory complications have been described in detail with the use of ticagrelor, other less frequent adverse effects are not so well clarified. We report the case of a patient with a systemic inflammatory response syndrome secondary to the use of ticagrelor.
El ticagrelor es un antiagregante plaquetario que actúa a través de la unión reversible a los receptores P2Y12 de la adenosina-difosfato. En el síndrome coronario agudo, ha demostrado reducir el riesgo de eventos cardiovasculares mayores como infarto de miocardio, accidente cerebrovascular y muerte. Si bien se han descripto en detalle ciertas complicaciones hemorrágicas, renales, hepáticas y respiratorias por el uso del ticagrelor, otros efectos adversos menos frecuentes de la droga no han sido adecuadamente esclarecidos. Presentamos el caso de un paciente con un síndrome de respuesta inflamatoria sistémica secundario al uso de ticagrelor.
Assuntos
Síndrome Coronariana Aguda , Infarto do Miocárdio , Síndrome Coronariana Aguda/induzido quimicamente , Síndrome Coronariana Aguda/tratamento farmacológico , Adenosina/efeitos adversos , Humanos , Síndrome de Resposta Inflamatória Sistêmica/induzido quimicamente , Ticagrelor/efeitos adversosRESUMO
Resumen El ticagrelor es un antiagregante plaquetario que actúa a través de la unión reversible a los receptores P2Y12 de la adenosina-difosfato. En el síndrome coronario agudo, ha demostrado reducir el riesgo de eventos cardiovasculares mayores como infarto de miocardio, accidente cerebrovascular y muerte. Si bien se han descripto en detalle ciertas complicaciones hemorrágicas, renales, hepáticas y respiratorias por el uso del ticagrelor, otros efectos adversos menos frecuentes de la droga no han sido adecuadamente escla recidos. Presentamos el caso de un paciente con un síndrome de respuesta inflamatoria sistémica secundario al uso de ticagrelor.
Abstract Ticagrelor is anantiplatelet agent which acts through reversible binding to the P2Y12 adenosine-diphosphate recep tors. In acute coronary syndromes it has been shown to reduce the risk of major cardiovascular events such as myocardial infarction, stroke and death. Although some hemorrhagic, kidney, liver and respiratory complications have been described in detail with the use of ticagrelor, other less frequent adverse effects are not so well clari fied. We report the case of a patient with a systemic inflammatory response syndrome secondary to the use of ticagrelor.