RESUMO
BACKGROUND: The aim of this article was to investigate whether prior aspirin use in patients with acute coronary syndromes affects clinical outcome. The Efficacy Safety Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events Study (ESSENCE) and Thrombolysis in Myocardial Infarction (TIMI) 11B trials have shown superiority of enoxaparin over unfractionated heparin (UFH) in patients with unstable angina and non-ST-segment elevation myocardial infarction (UA/NSTEMI). However, the treatment effect of enoxaparin in the subset of patients reporting prior aspirin use has not been determined. METHODS: The rate of death, myocardial infarction, and urgent revascularization at days 8 and 43 after randomization was compared among patients who received aspirin within the week before randomization with those who did not receive aspirin in the TIMI 11B trial. A total of 3275 patients (84%) were prior aspirin users. RESULTS: The admission diagnosis was similar for prior and nonprior aspirin users. At both day 8 and day 43 the event rate was higher for prior aspirin users than for nonprior aspirin users (odds ratio 1.6 [1.24-2.08], P =.0004 at day 43), even after correction for baseline characteristics. Compared with those prior aspirin users taking UFH, enoxaparin-treated prior aspirin users had a reduced rate of the composite end point of death, myocardial infarction, and urgent revascularization at day 8 (odds ratio 0.82 [0.67-1.00], P =.046) and day 43 (odds ratio 0.83 [0.70-0.98], P =.032). CONCLUSION: Patients with UA/NSTEMI and prior aspirin use had a 60% higher risk of death and cardiac ischemic events compared with nonprior aspirin users. On the basis of this subanalysis, enoxaparin is superior to UFH in all patients. In prior aspirin users the benefit is more clearly demonstrated.
Assuntos
Angina Instável/tratamento farmacológico , Anticoagulantes/uso terapêutico , Enoxaparina/uso terapêutico , Heparina/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Aspirina/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/uso terapêutico , Prognóstico , Medição de Risco , SíndromeRESUMO
The use of magnesium in the current therapeutics of acute myocardial infarction is controversial. There are theoretical bases on possible benefit mechanisms of action, whereby the magnesium have unique properties of myocardial cyto-protection, mainly reperfusion injury. The fundamental aspects about metabolic vias of magnesium, and the pathophysiologic explanations for the beneficial effect of magnesium included prevention of arrhythmia, antiplatelet effect, prevention of reperfusion injury, coronary vasodilation. Deleterious effects are outlined. The results of the main trials have originated considerable discussions in the world cardiology community. The principal differences between these trials and the possible explanations in order to interpret the results are explained.
Assuntos
Magnésio/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Hemodinâmica/efeitos dos fármacos , Humanos , Magnésio/farmacologia , Traumatismo por Reperfusão Miocárdica , Miocárdio/patologia , NecroseRESUMO
BACKGROUND: Low-molecular-weight heparins are attractive alternatives to unfractionated heparin (UFH) for management of unstable angina/non-Q-wave myocardial infarction (UA/NQMI). METHODS AND RESULTS: Patients (n=3910) with UA/NQMI were randomized to intravenous UFH for >/=3 days followed by subcutaneous placebo injections or uninterrupted antithrombin therapy with enoxaparin during both the acute phase (initial 30 mg intravenous bolus followed by injections of 1.0 mg/kg every 12 hours) and outpatient phase (injections every 12 hours of 40 mg for patients weighing <65 kg and 60 mg for those weighing >/=65 kg). The primary end point (death, myocardial infarction, or urgent revascularization) occurred by 8 days in 14.5% of patients in the UFH group and 12.4% of patients in the enoxaparin group (OR 0.83; 95% CI 0.69 to 1.00; P=0. 048) and by 43 days in 19.7% of the UFH group and 17.3% of the enoxaparin group (OR 0.85; 95% CI 0.72 to 1.00; P=0.048). During the first 72 hours and also throughout the entire initial hospitalization, there was no difference in the rate of major hemorrhage in the treatment groups. During the outpatient phase, major hemorrhage occurred in 1.5% of the group treated with placebo and 2.9% of the group treated with enoxaparin (P=0.021). CONCLUSIONS: Enoxaparin is superior to UFH for reducing a composite of death and serious cardiac ischemic events during the acute management of UA/NQMI patients without causing a significant increase in the rate of major hemorrhage. No further relative decrease in events occurred with outpatient enoxaparin treatment, but there was an increase in the rate of major hemorrhage.
Assuntos
Angina Instável/tratamento farmacológico , Enoxaparina/uso terapêutico , Fibrinolíticos/uso terapêutico , Heparina/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Terapia Trombolítica , Doença Aguda , Idoso , Angina Instável/complicações , Angina Instável/cirurgia , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Creatina Quinase/sangue , Método Duplo-Cego , Eletrocardiografia , Emergências , Enoxaparina/administração & dosagem , Enoxaparina/efeitos adversos , Europa (Continente)/epidemiologia , Inibidores do Fator Xa , Feminino , Fibrinolíticos/administração & dosagem , Fibrinolíticos/efeitos adversos , Hemorragia/induzido quimicamente , Heparina/administração & dosagem , Heparina/efeitos adversos , Humanos , Isoenzimas , Tábuas de Vida , Masculino , Pessoa de Meia-Idade , Mortalidade , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/prevenção & controle , Infarto do Miocárdio/cirurgia , Revascularização Miocárdica/estatística & dados numéricos , América do Norte/epidemiologia , Tempo de Tromboplastina Parcial , Recidiva , Segurança , América do Sul/epidemiologia , Terapia Trombolítica/efeitos adversos , Resultado do TratamentoRESUMO
The well-documented disadvantages of unfractionated heparin in the management of coronary syndromes, such as unpredictable bioavailability and maintenance of therapeutic range, has prompted several studies into the benefits of low-molecular-weight heparins (LMWHs). The favorable pharmacologic properties of LMWHs include a binding affinity for antithrombin III, anti-factor IIa activity, excellent bioavailability, minimal protein binding, predictable anticoagulant response, and clinical tolerance by patients. LMWHs are also characterized by having a specific anti-factor Xa effect and inducing only a small prolongation in general clotting tests-i.e., activated partial thromboplastin time, prothrombin time, and antithrombin activity-when used in high doses. Several studies have recently demonstrated that LMWHs are superior to placebo and are at least equal or superior to standard heparin when added to aspirin for the treatment of unstable angina and following non-Q-wave myocardial infarction. These studies, which include Thrombolysis in Myocardial Infarction (TIMI) 11A and Efficacy and Safety of Subcutaneous Enoxaparin versus intravenous unfractionated heparin in Non-Q-wave Coronary Events (ESSENCE), will be reviewed and discussed.