Antiagregación en el síndrome coronario agudo sin elevación del segmento ST en adultos mayores - hipótesis popular age / Antiplatelet Therapy in Non-ST-Segment Elevation Acute Coronary Syndromes in Elderly Patients. POPular AGE Hypothesis

RESUMEN Introducción: El estudio POPular AGE demostró que, en pacientes mayores de 70 años, el clopidogrel sería el inhibidor del receptor P2Y12 (iP2Y12) de elección por su asociación con menor incidencia de sangrado, sin diferencia en eventos isquémicos. Objetivos: Analizar la seguridad y eficacia de los diferentes esquemas de tratamiento con iP2Y12 en mayores de 70 años con síndrome coronario agudo sin elevación del segmento ST (SCASEST), a fin de contrastar la hipótesis "POPular AGE" en el mundo real. Material y métodos: Para el presente subanálisis del registro prospectivo BUENOS AIRES I, se analizaron datos correspondientes a 1100 pacientes de 21 centros médicos de Buenos Aires, Argentina, con seguimiento a 15 meses. Consideramos al subgrupo de pacientes mayores de 70 años, estratificados de acuerdo al iP2Y12 indicado al alta sanatorial. Resultados: Observamos gran carga de comorbilidades, con un 85,1% de hipertensión, 30,3% de diabetes mellitus y 43,2% de enfermedad renal crónica. Los pacientes tratados con ticagrelor/prasugrel (n = 54) presentaron mayor prevalencia de tabaquismo activo, menor fibrilación auricular y menor puntaje de score CRUSADE, sin diferencias en el puntaje de score GRACE, en relación a los tratados con clopidogrel (n = 286). A 15 meses de seguimiento, en la tasa, con más eventos de sangrado BARC ≥ 2 en el grupo clopidogrel (25,4% vs. 18,2%) aunque sin diferencias significativas (p = 0,327), y beneficio en la incidencia de eventos adversos cardiovasculares mayores (MACE) en el grupo de tratamiento con ticagrelor/prasugrel (18,6% vs 36,3%, p = 0,023). Conclusiones: En pacientes con SCASEST mayores de 70 años, adecuadamente seleccionados, el tratamiento con ticagrelor/ prasugrel podría ser una estrategia segura y efectiva.

ABSTRACT Background: The POPular AGE study demonstrated that in patients over 70 years of age clopidogrel would be the P2Y12 receptor inhibitor (P2Y12i) of choice due to its association with lower bleeding incidence and no difference in ischemic events. Objective: We analyzed the safety and efficacy of different treatment regimens with P2Y12i, in patients ≥70 years with nonST-segment elevation acute coronary syndromes (NSTE-ACS) to test the "POPular AGE" hypothesis in the real world. Methods: This subanalysis of the prospective BUENOS AIRES I registry analyzed data corresponding to 1100 patients from 21 medical centers in Buenos Aires, Argentina, followed-up for 15 months. We considered the subgroup of patients ≥70 years, stratified according to the P2Y12i indicated at discharge. Results: This subgroup had a high burden of comorbidities, with 85.1% hypertension, 30.3% diabetes mellitus, and 43.2% chronic kidney disease. Patients treated with ticagrelor/prasugrel (n=54) presented with higher prevalence of active smoking, less atrial fibrillation and lower CRUSADE score, with no differences in the GRACE score, compared whit those treated with clopidogrel (n=286). At the 15-month follow-up, no significant differences were observed in the BARC ≥2 bleeding rate, with more events in the clopidogrel group (25.4% vs. 18.2%; p=0.327) and a benefit in the incidence of major adverse cardiovascular events (MACE) in the ticagrelor/prasugrel treatment group (18.6% vs 36.3%, p= 0.023). Conclusions: In adequately selected patients with NSTE-ACS ≥70 years, treatment with ticagrelor/prasugrel could be a safe and effective strategy.

Continuous Use of Thienopyridine May Be as Safe as Low-Dose Aspirin in Endoscopic Resection of Gastric Tumors

BACKGROUND/AIMS: Current guidelines recommend withholding antiplatelets for 5–7 days before high-risk endoscopic procedures. We investigated whether this reduces post-endoscopic submucosal dissection (ESD) bleeding. METHODS: Gastric ESD cases with antiplatelets were retorospectively reviewed. Withholding antiplatelets for 5–7 days before ESD was defined as cessation and 0–4 days as continuation. The rate and risk of post-ESD bleeding according to the types and cessation of antiplatelets were assessed. RESULTS: Among the 215 patients (117 adenoma and 98 early gastric cancer), 161 patients were on single (94 aspirin, 56 thienopyridine, and 11 other agents), 51 on dual, and 3 on triple antiplatelets. Post-ESD bleeding rates were 12.8% in aspirin users, 3.6% in thienopyridine, 27.5% in dual, 33.3% in triple therapy, and 9.7% in the cessation and 15.0% in the continuation group. Multiple antiplatelets (odds ratio [OR], 2.41; 95% confidence interval [CI], 1.01 to 5.76) and specimen size ≥ 5.5 cm (OR, 2.84; 95% CI, 1.04 to 7.73) were the risk of bleeding, while continuation of thienopyridine (OR, 0.23; 95% CI, 0.05 to 1.09) and antiplatelets (OR, 1.83; 95% CI, 0.68 to 4.94) did not increase the risk of bleeding. CONCLUSIONS: Continuing thienopyridine and aspirin did not increase the risk of post-ESD. Multiple antiplatelet therapy and a large specimen size were independent risk factors of post-ESD bleeding.

Prasugrel-Induced Hypersensitivity Skin Reaction

We report a case of hypersensitivity skin reaction to prasugrel. The patient exhibited a generalized skin rash after treatment with prasugrel, which was resolved after discontinuation of prasugrel and substitution to clopidogrel. Clopidogrel was successfully administered as an alternative to prasugrel without any signs of further hypersensitivity.

A QSAR and molecular modeling study on a series of 3, 4-dihydro-1-isoquinolinamines and thienopyridines acting as nitric oxide synthase inhibitors.

A quantitative structure-activity relationship (QSAR) and molecular modeling study were performed on a series of 3,4-dihyro-1-isoquinolinamines and thienopyridines reported by Beaton et al. [Beaton et al. (2001) Bioorg Med Chem Lett 11, 1023-1026, 1027-1030] as potent, highly selective inhibitors of two isoforms of nitric oxide synthase (NOS) — neuronal NOS (nNOS) and endothelial NOS (eNOS), in order to find the physicochemical properties that governed their activity and the mode of interaction with the receptors, so that still more potent compounds in the series could be suggested. A multiple regression analysis revealed that nNOS and eNOS inhibition potency of these compounds could be controlled by their hydrophobic property and molar refractivity, respectively. Thus, nNOS and eNOS inhibition was indicated to involve the hydrophobic interaction and steric effects, respectively, suggesting some structural differences of the two isoforms of NOS. Based on the correlations obtained, some new, more potent compounds belonging to the series were predicted. These compounds were then docked into the receptors to see their interactions and find out the docking scores. The docked structures of two representative compounds, whose interaction energies with nNOS and eNOS, respectively were found to be the lowest, were given as an example to exhibit the possible orientation of the compounds to interact with the receptors.

The Significance of Clopidogrel Low-Responsiveness on Stent Thrombosis and Cardiac Death Assessed by the Verifynow P2Y12 Assay in Patients With Acute Coronary Syndrome Within 6 Months After Drug-Eluting Stent Implantation

BACKGROUND AND OBJECTIVES: Clopidogrel resistance or low-responsiveness may be associated with recurrent atherothrombotic events after drug-eluting stent (DES) implantation. We prospectively evaluated the association between clopidogrel resistance assessed by the Verifynow(TM) P2Y12 assay (Accumetrics, San Diego, CA, USA) and stent thrombosis (ST) or cardiac death (CD) in patients with acute coronary syndrome (ACS) within 6 months after DES implantation. SUBJECTS AND METHODS: We enrolled 237 consecutive patients (160 males, 65.2+/-10.3 years) with ACS who received a DES implantation. The composite endpoint was defined to CD or ST by Academic Research Consortium definitions within 6 months post-implantation. Clopidogrel resistance was defined as <20% inhibition of the P2Y12 receptor. RESULTS: Baseline demographic characteristics were similar between 142 normal individuals and 95 clopidogrel resistant patients. CD occurred in one case (0.7%) in the normal group and two cases (2.13%) in the resistant group (p=0.344). There was no episode of ST in the normal group and four episodes in the resistant group (4.2%, four definite ST) (p=0.035). Univariate logistic regression revealed an adjusted odds ratio (OR) for composite end point of CD or ST of 9.646 {95% confidence interval (CI) 1.139-81.679}, and multivariate logistic regression for composite end point revealed an OR of 12.074 (95% CI 1.205-120.992). CONCLUSION: Clopidogrel low-responsiveness assessed by the Verifynow(TM) P2Y12 assay is an independent predictor of ST and composite end point of ST or CD in patients with ACS within 6 months after DES implantation.