Terapêutica antitrombótica adjuvante no enfarte do miocárdio com supra-desnivelamento do segmento ST : revisão narrativa

© 2019 Sociedade Portuguesa de Cardiologia. Published by Elsevier España, S.L.U. All rights reserved.This article reviews the major pharmacologic features of, and clinical evidence on, adjuvant medical therapy in patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention. These drugs include oral antiplatelets (aspirin and P2Y12 inhibitors such as clopidogrel, prasugrel and ticagrelor), intravenous antiplatelet agents (the P2Y12 inhibitor cangrelor, GP IIb/IIIa inhibitors such as abciximab, eptifibatide and tirofiban), and intravenous anticoagulant agents (unfractionated heparin, low molecular weight heparin and bivalirudin).Neste artigo foram analisadas as principais características farmacológicas e a evidência clínica do uso de terapêutica médica adjuvante em doentes com enfarte do miocárdio com supradesnivelamento do segmento ST tratados com angioplastia primária. Esses fármacos incluem antiagregantes orais (ácido acetilsalicílico e inibidores de P2Y12, tais como clopidogrel, prasugrel, ticagrelor), antiagregantes endovenosos (o inibidor P2Y12 cangrelor, inibidores GpIIbIIIa, como o abciximab, eptifibatide e tirofiban) e agentes anticoagulantes de uso endovenoso (heparina não fracionada, heparina de baixo peso molecular e bivalirudina).info:eu-repo/semantics/publishedVersio

Effects of lipid-lowering treatment on platelet function and hemostatic mechanisms in diabetic patients : influence of chronic kidney disease and inflammatory parameters

Diabetes mellitus (DM) and chronic kidney disease (CKD) are both associated with increased cardiovascular morbidity and mortality, and the risk is even higher when they are concurrent. Both diseases are considered to be prothrombotic states with increased inflammatory activity and major disturbances in the hemostasis. Lipid-lowering treatment (LLT) may have beneficial effects on inflammation, platelet activation and atherothrombotic mechanisms. We evaluated the prognostic implications of impaired renal function, measured as estimated creatinine clearance (eCrCl), in 808 patients with stable angina pectoris in a post hoc analysis of the Angina Prognosis Study In Stockholm (APSIS), which compared metoprolol and verapamil treatment in stable angina with a median follow-up of 40 months. A multivariate Cox analysis showed an independent prognostic importance of eCrCl for cardiovascular (CV) death and for CV death or myocardial infarction (MI). Patients with eCrCl <60 ml/min had a doubled risk of suffering CV death or MI, compared to patients with eCrCl ≥90 ml/min. We investigated the effects of LLT with simvastatin alone or in combination with ezetimibe in 18 patients with an estimated GFR (eGFR) of 15-59 ml/min/1.73m2 (DM-CKD) and 21 DM patients with eGFR >75 ml/min/1.73m2 (DM-only) in a randomized, double blind, cross- over study. Parameters reflecting platelet activity, microparticles (MP) formation and inflammatory parameters were measured. At baseline, after a placebo run-in period, we found signs of increased inflammatory activity, increased platelet activation and hypercoagulability in DM-CKD compared to DM-only patients with increased formation of platelet-leukocyte aggregates (PLA), elevated levels of proinflammatory cytokines and soluble CD40L (sCD40L) in plasma, as well as elevated levels of MPs derived from platelets (PMPs), monocytes (MMPs) and endothelial cells. Simvastatin treatment alone reduced the expression of P-selectin, tissue factor (TF) and CD40L on PMPs, and TF on MMPs in both patient groups. Simvastatin also reduced levels of total procoagulant MPs, PMPs and MMPs as well as IFNγ and MCP-1 in DM-CKD but not in DM-only patients. Furthermore, the combination of simvastatin+ezetimbe reduced PLA formation and sCD40L levels in DM patients with CKD compared to DM-only patients. Most differences between DM-CKD and DM-only patients were reduced or disappeared with LLT despite similar lipid levels in the two groups both before and during LLT. In conclusion, impaired renal function carries independent prognostic information in patients with stable angina pectoris, in agreement with findings in other patient categories. Patients with CKD should be identified early, as there is need for improved CV risk reduction therapy in these high-risk patients. DM patients with CKD stages 3-4 (eGFR 15-59 mL/min/1.73m2) have signs of increased inflammatory activity and platelet activation, and hypercoagulability compared to DM-patients with normal eGFR. LLT counteracted the differences between DM-CKD and DM-only patients, with reduced inflammatory activation and a less procoagulant milieu especially in the presence of CKD. This may contribute to the beneficial effects of LLT on atherothrombotic complications in DM patients with concurrent CKD