CARLOS ALBERTO KENJI NAKASHIMA
Projetos de Pesquisa
Unidades Organizacionais
LIM/11 - Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação, Hospital das Clínicas, Faculdade de Medicina
5 resultados
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- Influence of Direct Thrombin Inhibitor and Low Molecular Weight Heparin on Platelet Function in Patients with Coronary Artery Disease: A Prospective Interventional Trial(2020) ARANTES, Flavia B. B.; MENEZES, Fernando R.; FRANCI, Andre; BARBOSA, Carlos J. D. G.; DALCOQUIO, Talia F.; NAKASHIMA, Carlos A. K.; BARACIOLI, Luciano M.; FURTADO, Remo H. M.; NOMELINI, Quintiliano S. S.; RAMIRES, Jose A. F.; KALIL FILHO, Roberto; NICOLAU, Jose C.Introduction The interaction between anticoagulants and platelet function is complex. Previous publications showed mixed results regarding the role of heparins in platelet aggregation. On the other hand, the direct thrombin inhibitor (DTI) dabigatran might enhance the risk of myocardial infarction in patients with atrial fibrillation, which could be related to increased platelet aggregability. Methods This was a prospective, interventional study of patients with chronic coronary artery disease (CAD) taking low-dose aspirin. The objective of the current study was to compare the effects of dabigatran versus enoxaparin on platelet aggregability. Subjects initially were on orally administered dabigatran for 5 days followed by subcutaneously administered enoxaparin after a 30-day washout period. Platelet function was assessed at baseline and after each intervention by multiple electrode aggregometry (MEA-ASPI) (primary endpoint), serum thromboxane B2 (TXB2), VerifyNow Aspirin (TM), and coagulation tests (secondary endpoints). Results Compared to baseline MEA-ASPI values, dabigatran increased platelet aggregation while enoxaparin decreased platelet aggregation (+ 5 U +/- 24.1 vs - 6 U +/- 22.2, respectively, p = 0.012). The TXB2 assay showed the same pattern (+ 2 pg/ml for dabigatran vs - 13 pg/ml for enoxaparin, p = 0.011). None of the additional tests showed significant differences between the groups. Individually, compared to baseline TXB2 results, enoxaparin significantly decreased platelet activation [33 (16.5-95) pg/mL vs 20 (10-52) pg/mL, respectively, p = 0.026], but no significant differences were observed with dabigatran. Conclusions DTI and anti-Xa drugs exert opposite effects on platelet function. A significant decrease in platelet activation through COX1 (also known as prostaglandin G/H synthase 1) was observed with enoxaparin, but no significant differences in platelet function were observed with dabigatran.
- Platelet Reactivity in Patients With Acute Coronary Syndromes Awaiting Surgical Revascularization(2021) NAKASHIMA, Carlos A. K.; DALLAN, Luis A. O.; LISBOA, Luiz A. F.; JATENE, Fabio B.; HAJJAR, Ludhmila A.; SOEIRO, Alexandre M.; FURTADO, Remo H. M.; DALCOQUIO, Talia F.; BARACIOLI, Luciano M.; LIMA, Felipe G.; V, Roberto R. C. Giraldez; SILVA, Bianca A.; COSTA, Mateus S. S.; STRUNZ, Celia M. C.; DALLAN, Luis R. P.; BARBOSA, Carlos J. D. G.; BRITTO, Flavia A. B.; FARKOUH, Michael E.; GURBEL, Paul A.; NICOLAU, Jose C.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 P2Y(12) receptor inhibitors, were assigned to either control group, P2Y(12) 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 (predefined 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. (C) 2021 by the American College of Cardiology Foundation.
- Factors associated with actively working in the very long-term following acute coronary syndrome(2021) NICOLAU, Jose C.; FURTADO, Remo H. M.; DALCOQUIO, Talia F.; LARA, Livia M.; JULIASZ, Marcela G.; FERRARI, Aline G.; NAKASHIMA, Carlos A. K.; FRANCI, Andre; PEREIRA, Cesar A. C.; LIMA, Felipe G.; GIRALDEZ, Roberto R.; SALSOSO, Rocio; BARACIOLI, Luciano M.; GOODMAN, ShaunOBJECTIVES: Returning to work after an episode of acute coronary syndrome (ACS) is challenging for many patients, and has both personal and social impacts. There are limited data regarding the working status in the very long-term after ACS. METHODS: We retrospectively analyzed 1,632 patients who were working prior to hospitalization for ACS in a quaternary hospital and were followed-up for up to 17 years. Adjusted models were developed to analyze the variables independently associated with actively working at the last contact, and a prognostic predictive index for not working at follow-up was developed. RESULTS: The following variables were significantly and independently associated with actively working at the last contact: age> median (hazard-ratio [HR], 0.76, p <0.001); male sex (HR, 1.52, p <0.001); government health insurance (HR, 1.36, p <0.001); history of angina (HR, 0.69, p <0.001) or myocardial infarction (MI) (HR, 0.76, p=0.005); smoking (HR, 0.81, p=0.015); ST-elevation MI (HR, 0.81, p=0.021); anterior-wall MI (HR, 0.75, p=0.001); non-primary percutaneous coronary intervention (PCI) (HR, 0.77, p=0.002); fibrinolysis (HR, 0.61, p<0.001); cardiogenic shock (HR, 0.60, p=0.023); statin (HR, 3.01, p < 0.001), beta-blocker (HR, 1.26, p=0.020), angiotensin-converting enzyme (ACE) inhibitor/angiotensin II receptor blocker (ARB) (HR, 1.37, p=0.001) at hospital discharge; and MI at follow-up (HR, 0.72, p=0.001). The probability of not working at the last contact ranged from 24.2% for patients with no variables, up to 80% for patients with six or more variables. CONCLUSIONS: In patients discharged after ACS, prior and in-hospital clinical variables, as well as the quality of care at discharge, have a great impact on the long-term probability of actively working.
- Increased bodyweight and inadequate response to aspirin in individuals with coronary artery disease(2019) FURTADO, Remo H. M.; GIUGLIANO, Robert P.; DALCOQUIO, Talia F.; ARANTES, Flavia B. B.; BARBOSA, Carlos J. D. G.; GENESTRETI, Paulo R. R.; FRANCI, Andre; MENEZES, Fernando R.; NAKASHIMA, Carlos A. K.; SCANAVINI FILHO, Marco A.; FERRARI, Aline G.; SALSOSO, Rocio; BARACIOLI, Luciano M.; NICOLAU, Jose C.Recent reports have suggested that aspirin effect might be influenced by bodyweight, with decreased efficacy in heavier individuals. We investigated the influence of bodyweight on aspirin pharmacodynamics in two independent datasets of patients taking non-enteric coated aspirin 100mg QD for coronary artery disease (CAD). In the first dataset, 368 patients had their platelet aggregation assessed using VerifyNow Aspirin and measured in Aspirin Reaction Units (ARU). In the second dataset, 70 patients had serum thromboxane B2 (TXB2) dosage assessed by an ELISA assay and measured in pg/mL. Platelet aggregation was independently associated with bodyweight, with 8.41 (95% CI 1.86-14.97; adjusted p-value=0.012) increase in ARU for every 10kg. Furthermore, the rate of non-response to aspirin (defined as ARU550) was significantly associated with increased bodyweight (adjusted p-value=0.007), with OR=1.23 (95% CI 1.06-1.42) for every 10kg. Similar results were found considering body mass index (in kg/m(2)), with 15.5 (95% CI 5.0 to 25.9; adjusted p-value=0.004) increase in ARU for every 10kg and non-response OR=1.43 (95% CI 1.13 to 1.81, adjusted p-value=0.003) for every 5kg/m(2). Moreover, serum TXB2 was higher in patients weighting more than 70kg (222.6 +/- 62.9 versus 194.9 +/- 61.9pg/mL; adjusted p-value=0.018). In two different datasets of patients with CAD on non-enteric coated aspirin 100mg QD, increased bodyweight was independently associated with impaired response to aspirin.
- Association between Statin Therapy and Lower Incidence of Hyperglycemia in Patients Hospitalized with Acute Coronary Syndromes(2021) FURTADO, Remo Holanda de Mendonca; GENESTRETI, Paulo Rizzo; DALCOQUIO, Talia F.; BARACIOLI, Luciano Moreira; LIMA, Felipe Galego; FRANCI, Andre; V, Roberto R. C. Giraldez; MENEZES, Fernando R.; FERRARI, Aline Gehlen; LIMA, Viviane Moreira; PEREIRA, Cesar A. C.; NAKASHIMA, Carlos Alberto Kenji; SALSOSO, Rocio; GODOY, Lucas Colombo; NICOLAU, Jose C.Background: Increased risk of new-onset diabetes with statins challenges the long-term safety of this drug class. However, few reports have analyzed this issue during acute coronary syndromes (ACS). Objective: To explore the association between early initiation of statin therapy and blood glucose levels in patients admitted with ACS. Methods: This was a retrospective analysis of patients hospitalized with ACS. Stain-naive patients were included and divided according to their use or not of statins within the first 24 hours of hospitalization. The primary endpoint was incidence of in-hospital hyperglycemia (defined as peak blood glucose > 200 mg/dL). Multivariable linear and logistic regression models were used to adjust for confounders, and a propensity-score matching model was developed to further compare both groups of interest. A p-value of less than 0.05 was considered statistically significant. Results: A total of 2,357 patients were included, 1,704 of them allocated in the statin group and 653 in the non-statin group. After adjustments, statin use in the first 24 hours was associated with a lower incidence of in-hospital hyperglycemia (adjusted OR=0.61, 95% Cl 0.46-0.80; p < 0.001) and lower need for insulin therapy (adjusted OR = 0.56, 95% CI 0.41-0.76; p < 0.001). Mese associations remained similar in the propensity-score matching models, as well as after several sensitivity analyses, such as after excluding patients who developed cardiogenic shock, severe infection or who died during index-hospitalization. Conclusions: Among statin-naive patients admitted with ACS, early statin therapy was independently associated with lower incidence of inhospital hyperglycemia.