RESUMEN
BACKGROUND: Pretreatment with oral P2Y12 inhibitors is a standard practice for ST-elevation myocardial infarction (STEMI) patients undergoing percutaneous coronary intervention (PCI). However, the efficacy and safety of P2Y12 inhibitors pretreatment remain unclear. OBJECTIVES: We conducted a meta-analysis to investigate the impact of P2Y12 inhibitor pretreatment on thrombotic and hemorrhagic endpoints in STEMI patients. METHODS: We searched multiple databases for studies that compared P2Y12 inhibitor pretreatment with no pretreatment in STEMI patients and reported endpoints of interest. Random effects model was used for the meta-analysis. RESULTS: Our meta-analysis included 3 randomized controlled trials and 14 observational studies, comprising 70,465 patients assigned to either P2Y12 inhibitor pretreatment (50,328 patients) or no pretreatment (20,137 patients). Compared to no pretreatment, P2Y12 inhibitor pretreatment did not result in significant reductions in all-cause mortality (risk ratio [RR] 0.73; 95% confidence interval [CI]: 0.52-1.03; p = 0.07), myocardial infarction (RR 0.75; 95% CI: 0.53-1.07; p = 0.11), or major bleeding (RR 0.80; 95% CI: 0.56-1.16; p = 0.22) at 30 days. However, our subgroup analysis revealed that P2Y12 inhibitor pretreatment administered in the pre-hospital setting was associated with a significant reduction in the incidence of myocardial infarction compared to no pretreatment (RR 0.73; 95% CI: 0.56-0.91; p < 0.01). CONCLUSION: Our analysis suggests that pretreatment with oral P2Y12 inhibitors before PCI in patients with STEMI was not associated with reduced all-cause mortality, myocardial infarction, or major bleeding. However, pretreatment with P2Y12 inhibitors in the pre-hospital setting appears to be beneficial in reducing reinfarction.
Asunto(s)
Infarto del Miocardio , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Humanos , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Infarto del Miocardio con Elevación del ST/terapia , Inhibidores de Agregación Plaquetaria/efectos adversos , Intervención Coronaria Percutánea/efectos adversos , Resultado del Tratamiento , Infarto del Miocardio/etiología , Hemorragia/inducido químicamente , Antagonistas del Receptor Purinérgico P2Y/efectos adversos , Estudios Observacionales como AsuntoRESUMEN
In the field of interventional neuroradiology, antiplatelet agents are commonly used to prepare patients before the implantation of permanent endovascular materials. Among the available drugs, clopidogrel is the most frequently used one, but resistance phenomena are considered to be relatively common. Prasugrel and ticagrelor were recently added to the pharmacologic arsenal, but the safety of these agents in patients undergoing neurointerventional procedures is still a subject of discussion. The cumulative experience with both drugs is less extensive than that with clopidogrel, and the experience with patients in the neurology field is less extensive than in the cardiology domain. In the present article, we provide a narrative review of studies that investigated safety issues of oral P2Y12 inhibitors in interventional neuroradiology and discuss potential routes for future research.
Asunto(s)
Inhibidores de Agregación Plaquetaria , Antagonistas del Receptor Purinérgico P2Y , Clopidogrel , Humanos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Clorhidrato de Prasugrel , Antagonistas del Receptor Purinérgico P2Y/efectos adversos , Ticagrelor , Resultado del TratamientoRESUMEN
BACKGROUND: Dual antiplatelet therapy is recommended for patients with acute coronary syndromes (ACS). Approximately 10% to 15% of these patients will undergo coronary artery bypass graft (CABG) surgery for index events, and current guidelines recommend stopping clopidogrel at least 5 days before CABG. This waiting time has clinical and economic implications. OBJECTIVES: This study aimed to evaluate if a platelet reactivity-based strategy is noninferior to standard of care for 24-h post-CABG bleeding. METHODS: In this randomized, open label noninferiority trial, 190 patients admitted with ACS with indications for CABG and on aspirin and P2Y12 receptor inhibitors, were assigned to either control group, P2Y12 receptor inhibitor withdrawn 5 to 7 days before CABG, or intervention group, daily measurements of platelet reactivity by Multiplate analyzer (Roche Diagnostics GmbH, Vienna, Austria) with CABG planned the next working day after platelet reactivity normalization (pre-defined as ≥46 aggregation units). RESULTS: Within the first 24 h of CABG, the median chest tube drainage was 350 ml (interquartile range [IQR]: 250 to 475 ml) and 350 ml (IQR: 255 to 500 ml) in the intervention and control groups, respectively (p for noninferiority <0.001). The median waiting period between the decision to undergo CABG and the procedure was 112 h (IQR: 66 to 142 h) and 136 h (IQR: 112 to 161 h) (p < 0.001), respectively. In the intention-to-treat analysis, a 6.4% decrease in the median in-hospital expenses was observed in the intervention group (p = 0.014), with 11.2% decrease in the analysis per protocol (p = 0.003). CONCLUSIONS: A strategy based on platelet reactivity-guided is noninferior to the standard of care in patients with ACS awaiting CABG regarding peri-operative bleeding, significantly shortens the waiting time to CABG, and decreases hospital expenses. (Evaluation of Platelet Aggregability in the Release of CABG in Patients With ACS With DAPT; NCT02516267).
Asunto(s)
Síndrome Coronario Agudo/tratamiento farmacológico , Pruebas de Coagulación Sanguínea/instrumentación , Puente de Arteria Coronaria/estadística & datos numéricos , Antagonistas del Receptor Purinérgico P2Y/administración & dosificación , Tiempo de Tratamiento/estadística & datos numéricos , Síndrome Coronario Agudo/economía , Síndrome Coronario Agudo/cirugía , Anciano , Aspirina/administración & dosificación , Aspirina/efectos adversos , Transfusión Sanguínea/estadística & datos numéricos , Femenino , Costos de Hospital/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/efectos adversos , Hemorragia Posoperatoria/inducido químicamente , Hemorragia Posoperatoria/prevención & control , Cuidados Preoperatorios/instrumentación , Antagonistas del Receptor Purinérgico P2Y/efectos adversosRESUMEN
INTRODUCTION/OBJECTIVES: In patients who have undergone recent percutaneous coronary intervention (PCI), poor adhesion to antiplatelet agents may increase the risk of stent thrombosis and death. We aimed to investigate the adherence to different P2Y12 receptor inhibitors after PCI with drug-eluting stent in stable and unstable patients and to evaluate the factors associated with low adherence. METHOD: In a prospective study conducted between 2014 and 2018, the 8-item Morisky scale was applied at 30 days and 6 months post-PCI to measure P2Y12 receptor inhibitors adherence. Also, we describe the characteristics of patients using different platelet receptor P2Y12 inhibitors. Regression models were used to identify predictors of poor adherence. RESULTS: A total of 214 patients were included (65 ± 12 years, 81% man, 61% acute coronary syndromes). Patients in the clopidogrel group were older than those in the prasugrel (68 ± 12 vs 59 ± 11 years, P < .01, respectively) or ticagrelor group (68 ± 12 vs 62 ± 12 years, P < .01). Patients with low/moderate adherence at 30 days and 6 months represented, respectively, 19.8% and 27.5% of our sample. Current smokers and preexisting cardiovascular disease at presentation were associated with lower adherence at 30 days. CONCLUSIONS: We found substantial rates of moderate and low adherence to P2Y12 receptor inhibitors early after PCI. Current smokers and preexisting cardiovascular disease at presentation were associated with a lower likelihood of adherence. These results highlight the need of monitoring adherence to medical treatment after PCI.
Asunto(s)
Trombosis Coronaria/prevención & control , Stents Liberadores de Fármacos , Cumplimiento de la Medicación , Intervención Coronaria Percutánea/instrumentación , Inhibidores de Agregación Plaquetaria/uso terapéutico , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Anciano , Anciano de 80 o más Años , Comorbilidad , Trombosis Coronaria/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/mortalidad , Inhibidores de Agregación Plaquetaria/efectos adversos , Estudios Prospectivos , Antagonistas del Receptor Purinérgico P2Y/efectos adversos , Factores de Riesgo , Fumadores , Fumar/efectos adversos , Factores de Tiempo , Resultado del TratamientoRESUMEN
INTRODUCTION: Cardiovascular disease (CVD) is the main cause of death in the world. Coronary artery disease (CAD) is the most common form of CVD presentation, but the prevalence of peripheral artery disease (PAD) is increasing. Patients with polyvascular disease comprise a very high-risk population that has been infrequently studied. Areas covered: The authors review the current evidence of the efficacy and safety of ticagrelor in the setting of acute coronary syndrome and stable patients post-MI with and without PAD and summarize its pharmacokinetics, pharmacodynamics, and regulatory issues. Expert opinion: Randomized studies showed that ticagrelor is superior to clopidogrel in patients with acute coronary syndromes, and is superior to placebo in the chronic phase (>1 year) post-myocardial infarction. Sub-analyses of these studies suggest that patients with myocardial infarction and PAD, compared to patients without these characteristics, may have greater benefit with ticagrelor. Nonetheless, the global evidence about the role of ticagrelor in patients with myocardial infarction and PAD remains relatively sparse, and a prospective randomized trial testing this hypothesis would be necessary to provide more definite data regarding the efficacy and safety of ticagrelor in this very high-risk population.
Asunto(s)
Síndrome Coronario Agudo/prevención & control , Adenosina/análogos & derivados , Infarto del Miocardio/prevención & control , Enfermedad Arterial Periférica/prevención & control , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Síndrome Coronario Agudo/patología , Adenosina/efectos adversos , Adenosina/farmacocinética , Adenosina/uso terapéutico , Regulación Gubernamental , Semivida , Hemorragia/etiología , Humanos , Infarto del Miocardio/complicaciones , Infarto del Miocardio/patología , Enfermedad Arterial Periférica/complicaciones , Enfermedad Arterial Periférica/patología , Antagonistas del Receptor Purinérgico P2Y/efectos adversos , Antagonistas del Receptor Purinérgico P2Y/farmacocinética , Ticagrelor , Resultado del TratamientoRESUMEN
BACKGROUND: Current guidelines recommend early P2Y12 inhibitor administration in non-ST-elevation myocardial infarction, but it is unclear if precatheterization use is associated with longer delays to coronary artery bypass grafting (CABG) or higher risk of post-CABG bleeding and transfusion. This study examines the patterns and outcomes of precatheterization P2Y12 inhibitor use in non-ST-elevation myocardial infarction patients who undergo CABG. METHODS AND RESULTS: Retrospective analysis was done of 20 304 non-ST-elevation myocardial infarction patients in the ACTION (Acute Coronary Treatment and Intervention Outcomes Network) Registry (2009-2014) who underwent catheterization within 24 hours of admission and CABG during the index hospitalization. Using inverse probability-weighted propensity adjustment, we compared time from catheterization to CABG, post-CABG bleeding, and transfusion rates between patients who did and did not receive precatheterization P2Y12 inhibitors. Among study patients, 32.9% received a precatheterization P2Y12 inhibitor (of these, 2.2% were given ticagrelor and 3.7% prasugrel). Time from catheterization to CABG was longer among patients who received precatheterization P2Y12 inhibitor (median 69.9 hours [25th, 75th percentiles 28.2, 115.8] versus 43.5 hours [21.0, 71.8], P<0.0001), longer for patients treated with prasugrel (median 114.4 hours [66.5, 155.5]) or ticagrelor (90.4 hours [48.7, 124.5]) compared with clopidogrel (69.3 [27.5, 114.6], P<0.0001). Precatheterization P2Y12 inhibitor use was associated with a higher risk of post-CABG major bleeding (75.7% versus 73.4%, adjusted odds ratio 1.33, 95% confidence interval 1.22-1.45, P<0.0001) and transfusion (47.6% versus 35.7%, adjusted odds ratio 1.51, 95% confidence interval 1.41-1.62, P<0001); these relationships did not differ among patients treated with clopidogrel, prasugrel, or ticagrelor. CONCLUSIONS: Precatheterization P2Y12 inhibitor use occurs commonly among non-ST-elevation myocardial infarction patients who undergo early catheterization and in-hospital CABG. Despite longer delays to surgery, the majority of pretreated patients proceed to CABG <3 days postcatheterization. Precatheterization P2Y12 inhibitor use is associated with higher risks of postoperative bleeding and transfusion.
Asunto(s)
Plaquetas/efectos de los fármacos , Cateterismo Cardíaco , Angiografía Coronaria , Puente de Arteria Coronaria , Infarto del Miocardio sin Elevación del ST/cirugía , Inhibidores de Agregación Plaquetaria/administración & dosificación , Antagonistas del Receptor Purinérgico P2Y/administración & dosificación , Receptores Purinérgicos P2Y12/efectos de los fármacos , Anciano , Plaquetas/metabolismo , Transfusión Sanguínea , Cateterismo Cardíaco/efectos adversos , Cateterismo Cardíaco/mortalidad , Distribución de Chi-Cuadrado , Angiografía Coronaria/efectos adversos , Angiografía Coronaria/mortalidad , Puente de Arteria Coronaria/efectos adversos , Puente de Arteria Coronaria/mortalidad , Esquema de Medicación , Femenino , Hemorragia/inducido químicamente , Hemorragia/terapia , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Infarto del Miocardio sin Elevación del ST/sangre , Infarto del Miocardio sin Elevación del ST/diagnóstico por imagen , Infarto del Miocardio sin Elevación del ST/mortalidad , Oportunidad Relativa , Inhibidores de Agregación Plaquetaria/efectos adversos , Valor Predictivo de las Pruebas , Puntaje de Propensión , Modelos de Riesgos Proporcionales , Antagonistas del Receptor Purinérgico P2Y/efectos adversos , Receptores Purinérgicos P2Y12/sangre , Sistema de Registros , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Tiempo de Tratamiento , Resultado del TratamientoRESUMEN
BACKGROUND: Clopidogrel is by far the most prescribed platelet adenosine diphosphate (ADP) antagonist in Puerto Rico despite the advent of newer agents (prasugrel and ticagrelor). Given the paucity of data on clopidogrel responsiveness in Hispanics, we sought to determine the association between clinical characteristics and platelet reactivity in Puerto Rican patients on clopidogrel therapy. STUDY POPULATION: A total of 100 Puerto Rican patients on clopidogrel therapy were enrolled and allocated into two groups: Group I, without high on-treatment platelet reactivity (HTPR); and Group II, with HTPR. Platelet function was measured ex vivo using the VerifyNow® P2Y12 assay. RESULTS: The cohort was comprised of Hispanic patients with coronary artery disease (57%), peripheral artery disease (32%), carotid artery stenosis (7%), cerebral artery aneurysm (2%), and stroke (2%). Mean platelet reactivity was 200 ± 61 P2Y12 reaction units (PRUs) (range: 8-324), and 35% of patients had HTPR (PRUs ⩾ 230). Multivariable logistic regression analysis determined that diabetes mellitus (DM) [odds ratio (OR) = 3.27; 95% confidence interval (CI): 1.20-8.96], use of proton-pump inhibitors (PPIs) (OR = 3.60; 95% CI: 1.09-11.82), and calcium channel blockers (CCBs) (OR = 3.10; 95% CI: 1.09-8.83) were independent predictors of HTPR ( p < 0.05) after adjusting for other clinical variables. CONCLUSIONS: In a sample of 100 Puerto Rican Hispanic patients on clopidogrel, 35% had HTPR. Furthermore, DM, PPIs and CCBs predicted HTPR. Clinical outcome data are needed to identify appropriate PRU thresholds for risk prediction in the Puerto Rican population.
Asunto(s)
Plaquetas/efectos de los fármacos , Enfermedades Cardiovasculares/tratamiento farmacológico , Resistencia a Medicamentos , Hispánicos o Latinos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Ticlopidina/análogos & derivados , Anciano , Anciano de 80 o más Años , Plaquetas/metabolismo , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/etnología , Distribución de Chi-Cuadrado , Clopidogrel , Estudios Transversales , Femenino , Humanos , Modelos Lineales , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Inhibidores de Agregación Plaquetaria/efectos adversos , Pruebas de Función Plaquetaria , Valor Predictivo de las Pruebas , Puerto Rico/epidemiología , Antagonistas del Receptor Purinérgico P2Y/efectos adversos , Receptores Purinérgicos P2Y12/sangre , Receptores Purinérgicos P2Y12/efectos de los fármacos , Medición de Riesgo , Factores de Riesgo , Ticlopidina/efectos adversos , Ticlopidina/uso terapéutico , Resultado del TratamientoRESUMEN
INTRODUCTION: Therapeutic options for sickle cell disease (SCD) are limited and, currently, only one drug (hydroxyurea) has FDA approval for the treatment of adult SCD. While this genetic disease is caused by hemoglobin polymerization, subsequent downstream events trigger platelet activation, vaso-occlusion and the disease's complex pathophysiology. Areas covered: The oral thienopyridine, prasugrel hydrochloride, irreversibly inhibits the P2Y12 receptors, inhibiting ADP-dependent platelet activation. We discuss recent clinical trials evaluating the pharmokinetics of prasugrel and its potential for use in SCD. Expert opinion: Prasugrel administration in SCD appears to be well tolerated and safe. However, although this drug modestly inhibits platelet activity in these patients, administration of prasugrel to a large group of children and adolescents for up to 24 months failed to convincingly reduce vaso-occlusive complications. Speculatively, prasugrel may be of occasional use for off-license purposes in patients unable or unwilling to take hydroxyurea (particularly in 12-17-year olds). Although there is currently no prospect of prasugrel being licensed for use in SCD, the success of on-going trials of other antiplatelet agents in SCD might lead to further trials of prasugrel in SCD.