RESUMEN
BACKGROUND: Antiplatelet therapy is often discontinued in patients with drug-eluting stents who are undergoing surgical procedures. However, discontinuation of antiplatelet therapy is an important risk factor for late stent thrombosis. Our objective was to examine the safety of short-term discontinuation of antiplatelet therapy. METHODS AND RESULTS: We systematically searched Medline for reported cases of late stent thrombosis and very late stent thrombosis published between January 2001 and July 2008. We restricted our search to Academic Research Consortium-defined definite cases. We identified 161 cases of late stent thrombosis or very late stent thrombosis from 84 articles (79 from case reports, 61 from registries, and 21 from randomized clinical trials). Patients had a mean age of 58.4+/-13.4 years, and 88% were male. A total of 19 cases occurred in patients who were receiving dual antiplatelet therapy at the time of the event. If patients stopped both antiplatelet agents simultaneously, the median time to event was 7 days. If patients had previously stopped a thienopyridine with no ill effect and subsequently stopped acetylsalicylic acid, the median time to event was also 7 days from the time of acetylsalicylic acid cessation. If the thienopyridine was stopped but acetylsalicylic acid was maintained, the median time to event was 122 days. Among the 48 patients who stopped both agents, 36 cases (75%) occurred within 10 days. Among the 94 patients who discontinued a thienopyridine but continued acetylsalicylic acid, only 6 cases (6%) occurred within 10 days. CONCLUSIONS: If acetylsalicylic acid therapy is maintained, short-term discontinuation of a thienopyridine may be relatively safe in patients with drug-eluting stents.
Asunto(s)
Stents Liberadores de Fármacos/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Trombosis/etiología , Anciano , Aspirina/uso terapéutico , Estudios de Casos y Controles , Recolección de Datos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Femenino , Humanos , MEDLINE , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/efectos adversos , Piridinas/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Cardiovascular disease (CVD) is the leading cause of mortality in women. In fact, CVD is responsible for a third of all deaths of women worldwide and half of all deaths of women over 50 years of age in developing countries. The prevalence of CVD risk factor precursors is increasing in children. Retrospective analyses suggest that there are some clinically relevant differences between women and men in terms of prevalence, presentation, management and outcomes of the disease, but little is known about why CVD affects women and men differently. For instance, women with diabetes have a significantly higher CVD mortality rate than men with diabetes. Similarly, women with atrial fibrillation are at greater risk of stroke than men with atrial fibrillation. Historically, women have been underrepresented in clinical trials. The lack of good trial evidence concerning sex-specific outcomes has led to assumptions about CVD treatment in women, which in turn may have resulted in inadequate diagnoses and suboptimal management, greatly affecting outcomes. This knowledge gap may also explain why cardiovascular health in women is not improving as fast as that of men. Over the last decades, mortality rates in men have steadily declined, while those in women remained stable. It is also becoming increasingly evident that gender differences in cultural, behavioural, psychosocial and socioeconomic status are responsible, to various degrees, for the observed differences between women and men. However, the interaction between sex-and gender-related factors and CVD outcomes in women remains largely unknown.
Asunto(s)
Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Causas de Muerte , Calidad de Vida , Adolescente , Adulto , Factores de Edad , Anciano , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/epidemiología , Canadá/epidemiología , Niño , Enfermedad Coronaria/diagnóstico , Enfermedad Coronaria/epidemiología , Femenino , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/epidemiología , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Medición de Riesgo , Índice de Severidad de la Enfermedad , Distribución por Sexo , Factores Sexuales , Análisis de SupervivenciaRESUMEN
The binding of leukocyte P-selectin glycoprotein ligand-1 (PSGL-1) to platelet P-selectin is central to post-angioplasty restenosis. Although intracoronary stents limit the mechanical component of restenosis, they cause marked thrombo-inflammation and neointimal proliferation leading to greater late luminal loss. We sought to demonstrate that P-selectin antagonism, using recombinant PSGL-1 (rPSGL-Ig), is effective in reducing platelet-leukocyte reactions and in-stent restenosis in double-injured porcine coronary arteries. Two weeks after initial injury by angioplasty to the coronary arteries, stents were implanted at the injury-induced lesion site, 15 min after an i.v. bolus administration of a vehicle or rPSGL-Ig (1 mg/kg). Four weeks later, adhesion of (51)Cr-platelets and (111)In-neutrophils and histomorphometric analyses were performed. In-stent residual lumen was almost 3 fold larger in rPSGL-Ig-treated arteries (3.1 +/- 0.4 mm(2)) as compared to control (1.1 +/- 0.2 mm(2)), which correspond to 64% vascular stenosis in control with no change in rPSGL-Ig animals. For a similar injury score, in-stent neointima was significantly reduced by 30 to 40% in the rPSGL-Ig group and quantitative coronary angiography showed a significant 35% reduction in late lumen loss. These effects of rPSGL-Ig were associated with a respective 70% and 53% reduction in platelet and neutrophil adhesion. In conclusion, pretreatment with rPSGL-Ig reduces thrombo-inflammatory responses, neointimal proliferation, and in-stent restenosis. P-selectin antagonism offers a promising therapy to improve clinical outcomes of coronary stenting.
Asunto(s)
Reestenosis Coronaria/prevención & control , Glicoproteínas de Membrana/uso terapéutico , Stents/efectos adversos , Angioplastia/efectos adversos , Animales , Plaquetas/patología , Adhesión Celular/efectos de los fármacos , Inflamación/prevención & control , Leucocitos/patología , Proteínas Recombinantes , Porcinos , Trombosis/prevención & controlRESUMEN
P-selectin is translocated from the alpha-granules to the surface of activated platelets where it participates in thrombosis and inflammation. We investigated the signaling pathways involved in thrombin-induced human platelet P-selectin expression. Assessed by flow cytometry, inhibition of protein kinase C (PKC) with chelerythrine reduced P-selectin expression by 66%, platelet/neutrophil binding, GPIIb/IIIa activation and aggregation (p<0.05). Gö 6976, an inhibitor of the conventional PKCs (alpha and beta), did not alter P-selectin expression. However, rottlerin inhibited by 50% its expression (p<0.05), but only at doses that interfere with the novel (epsilon eta) and atypical (zeta) PKCs. Inhibition of protein tyrosine kinase (PTK) and phosphoinosi-tide 3-kinase (PI3-K) did not significantly affect P-selectin expression. In conclusion, thrombin-induced P-selectin expression is PKC-sensitive, but PTK and PI3-K-insensitive. The novel epsilon and eta and atypical zeta, but not the conventional alpha and beta and the novel delta PKCs, may be involved in this process.
Asunto(s)
Plaquetas/metabolismo , Selectina-P/biosíntesis , Proteína Quinasa C/fisiología , Plaquetas/ultraestructura , Humanos , Isoenzimas/fisiología , Selectina-P/análisis , Fosfatidilinositol 3-Quinasas , Proteínas Tirosina Quinasas , Vesículas Secretoras/metabolismo , Transducción de Señal , TrombinaRESUMEN
BACKGROUND: Coronary artery disease is a significant risk factor for atrial fibrillation (AF), but the basis for this association is incompletely understood. The present study evaluated the hypothesis that atrial ischemia can create a substrate for AF maintenance. METHODS AND RESULTS: Atrial ischemia was induced by occlusion of an atrial arterial branch that did not provide blood flow to the ventricles. Atrial-arterial occlusion increased the duration of AF induced by burst pacing from 57+/-32 seconds (control) to 803+/-214 seconds (P<0.001) after 0.5 hour of occlusion and to 887+/-209 seconds (P<0.001) after 3 hours of occlusion. Prolonged AF (>20 minutes) was induced in 0 of 16 dogs (0%) under control conditions, 7 of 16 (44%, P<0.01) at 0.5 to 3 hours, and 5 of 13 (38%, P<0.01) 3 to 5 hours after occlusion. Atrial conduction was slowed substantially within the ischemic zone: eg, conduction delay was 8+/-1 ms at a cycle length of 200 ms, control, versus 22+/-5 ms (P<0.01) after 0.5 hours and 27+/-5 ms (P<0.001) after 3 hours of ischemia. Refractoriness was initially unaffected but was prolonged 5 hours after occlusion. Phase-delay analysis and high-density mapping confirmed severe conduction slowing in the ischemic zone. Histological examination confirmed the location of ischemic regions and revealed extensive ischemia-induced necrosis at sites of conduction delay. CONCLUSIONS: Experimental atrial ischemia creates a substrate for AF maintenance, apparently by causing local conduction slowing that promotes reentry. These results suggest that atrial ischemia may significantly promote AF, and may be relevant to AF mechanisms in association with coronary artery disease.
Asunto(s)
Fibrilación Atrial/etiología , Atrios Cardíacos , Isquemia Miocárdica/complicaciones , Animales , Arritmias Cardíacas/etiología , Fibrilación Atrial/fisiopatología , Estimulación Cardíaca Artificial , Perros , Electrofisiología , Atrios Cardíacos/fisiopatología , Cinética , Isquemia Miocárdica/patologíaRESUMEN
P-selectin is rapidly translocated from platelet alpha-granules following activation. Intracellular cyclic AMP (cAMP) is a potent inhibitory pathway that results in global downregulation of platelet activation. While cAMP-dependent protein kinase (PKA) has long been considered as the main mediator of cAMP-dependent effects, no study has yet evaluated its effect on P-selectin expression in human platelets. Pretreatment of thrombin-stimulated platelets with forskolin resulted in a concentration- dependent inhibition of P-selectin expression that correlated with adenylyl cyclase activity. Inhibition of PKA with H-89 reversed cAMP-induced inhibition of P-selectin while cGMP-dependent protein kinase (PKG) inhibition with KT5823 significantly potentiated cAMP-dependent inhibition of P-selectin. Similar results were also observed in a platelet/neutrophil binding assay. In conclusion, cAMP-induced inhibition of P-selectin expression is, in large part, mediated through activation of PKA. PKG appears to be solicited for P-selectin expression when cAMP levels are elevated which suggest a cAMP/PKG-dependent pathway of platelet activation.