RESUMO
Direct oral anticoagulants (DOACs), including the direct thrombin inhibitor dabigatran and the direct factor Xa inhibitors rivaroxaban, apixaban and edoxaban have at least comparable efficacy as vitamin K antagonists along with a better safety profile, reflected by a lower incidence of intracranial hemorrhage. Specific reversal agents have been developed in recent years. Namely, idarucizumab, a specific antidote for dabigatran, is currently approved in most countries. Andexanet, which reverses factor Xa inhibitors, has been recently approved by the FDA, and ciraparantag, a universal antidote targeted to reverse all DOACs, is still under investigation. In this review we provide an update on the pharmacology of DOACs, the risk of hemorrhagic complications associated with their use, the measurement of their anticoagulant effect and the reversal strategies in case of DOAC-associated bleeding.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antitrombinas/administração & dosagem , Antitrombinas/efeitos adversos , Fatores de Coagulação Sanguínea/uso terapêutico , Hemorragia/induzido quimicamente , Hemorragia/terapia , Administração Oral , Antídotos/uso terapêutico , Dabigatrana/administração & dosagem , Dabigatrana/efeitos adversos , Humanos , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Piridinas/administração & dosagem , Piridinas/efeitos adversos , Piridonas/administração & dosagem , Piridonas/efeitos adversos , Fatores de Risco , Rivaroxabana/administração & dosagem , Rivaroxabana/efeitos adversos , Tiazóis/administração & dosagem , Tiazóis/efeitos adversosRESUMO
Direct oral anticoagulants (DOACs), including the direct thrombin inhibitor dabigatran and the direct factor Xa inhibitors rivaroxaban, apixaban and edoxaban have at least comparable efficacy as vitamin K antagonists along with a better safety profile, reflected by a lower incidence of intracranial hemorrhage. Specific reversal agents have been developed in recent years. Namely, idarucizumab, a specific antidote for dabigatran, is currently approved in most countries. Andexanet, which reverses factor Xa inhibitors, has been recently approved by the FDA, and ciraparantag, a universal antidote targeted to reverse all DOACs, is still under investigation. In this review we provide an update on the pharmacology of DOACs, the risk of hemorrhagic complications associated with their use, the measurement of their anticoagulant effect and the reversal strategies in case of DOAC-associated bleeding.
Assuntos
Humanos , Fatores de Coagulação Sanguínea/uso terapêutico , Antitrombinas/administração & dosagem , Antitrombinas/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Hemorragia/induzido quimicamente , Hemorragia/terapia , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Piridinas/administração & dosagem , Piridinas/efeitos adversos , Piridonas/administração & dosagem , Piridonas/efeitos adversos , Tiazóis/administração & dosagem , Tiazóis/efeitos adversos , Administração Oral , Fatores de Risco , Rivaroxabana/administração & dosagem , Rivaroxabana/efeitos adversos , Dabigatrana/administração & dosagem , Dabigatrana/efeitos adversos , Antídotos/uso terapêuticoRESUMO
OBJECTIVE: To evaluate the effects of glucose-insulin-potassium (GIK) therapy on infarct size and left ventricular function when used as an adjuvant therapy to primary angioplasty. DESIGN: Prospective, randomized, double-blind, placebo-controlled study. SETTING: Cardiac intensive care unit at a university hospital. PATIENTS: Thirty-seven patients with acute myocardial infarction for whom primary angioplasty was indicated. INTERVENTIONS: Eligible patients were randomized by a blinded pharmacist to GIK solution (30% glucose in water with insulin 50 U/L, and KCl 40 mM/L) vs. placebo at 1.5 mL/kg/hr for 24 hrs. MEASUREMENTS AND MAIN RESULTS: Tc 99m sestamibi myocardial scintigraphy was performed at admission and at 3 months. Primary end points were the changes in left ventricular ejection fraction (LVEF) and the size of salvaged myocardium. Baseline clinical characteristics were similar in both groups. At the 3-month follow-up, a significant overall decrease in infarct size (37 +/- 16% vs. 12 +/- 10%, p <.005) and an increase in LVEF (34 +/- 13% vs. 49 +/- 9%, p =.005) were observed. Patients randomized to GIK solution experienced a significant increase in their LVEF at 3 months (39 +/- 12 to 51 +/- 13, p =.002). Patients who received placebo had no significant differences between baseline and 3-month measurements (44 +/- 13 vs. 49 +/- 14, p = NS). There was a trend toward an increase in myocardial salvage in the GIK group, which did not reach statistical significance. When patients from both groups were compared directly, differences in LVEF improvement were no longer significant. CONCLUSIONS: GIK solution did not improve LVEF or decrease the infarct size among patients undergoing primary angioplasty.