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
BACKGROUND: The rapid utilization of fibrinolytics following Q-wave myocardial infarction has clearly modified the evolution of this disease. However, it is still not known whether the immediate inhibition of platelet aggregation (PA) during the coronary event improves outcomes. HYPOTHESIS: The present study was designed to test, in patients with known coronary artery disease (chronic stable angina), whether the particular kinetic pattern of lysine acetylsalicylate (LA) compared with aspirin may affect the time to onset of inhibition of platelet aggregation. METHODS: Ten patients suffering from chronic stable angina participated in this study to compare the efficacy and speed of the inhibition of PA with 320 mg of LA versus 320 mg of aspirin. All patients discontinued the use of aspirin and any other anti-inflammatory agents for 15 days prior to the beginning of the study. They were randomly assigned to LA or aspirin. Blood specimens were obtained to measure the PA at admission, and 5, 10, 20, 30, and 60 min after ingestion. Patients continued to take the assigned drug once a day for the following 4 days. On Day 5, a new blood sample was taken. After this, patients underwent a 15-day wash-out period, and then crossed over to the opposite drug. The samples were analyzed immediately using platelet-rich plasma stimulated with adenosine diphosphate (ADP) 2 mumol/l, collagen 1 microgram/ml, epinephrine 20 mumol/l, and sodium arachidonate acid 0.75 mm/l. RESULTS: The same level of PA inhibition after 30 and 60 min of aspirin administration can be obtained with LA 5 min following ingestion (sodium arachidonate acid: LA: 16.3 +/- 25.9 vs. aspirin 57.6 +/- 8.2; p = 0.00014; collagen: LA 18.9 +/- 20.1 vs. aspirin 47.2 +/- 10.5; p = 0.00092; ADP: LA 27.3 +/- 18.4 vs. aspirin 39.7 +/- 21.8, p = 0.18; epinephrine: LA 22.0 +/- 9.9 vs. aspirin 55.4 +/- 10.9, p = 0.00002. CONCLUSIONS: Platelet aggregation inhibition immediately following LA may have significant clinical implications for the treatment of coronary syndromes.
Assuntos
Angina Pectoris/tratamento farmacológico , Aspirina/análogos & derivados , Aspirina/farmacocinética , Lisina/análogos & derivados , Lisina/farmacocinética , Inibidores da Agregação Plaquetária/farmacocinética , Agregação Plaquetária/efeitos dos fármacos , Análise de Variância , Angina Pectoris/metabolismo , Angina Pectoris/fisiopatologia , Aspirina/farmacologia , Estudos Cross-Over , Feminino , Humanos , Lisina/farmacologia , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/farmacologia , Método Simples-Cego , Fatores de TempoRESUMO
OBJECTIVES: We analyzed the effect of the pharmacologic combination of 2 indirect antithrombin drugs--enoxaparin (low-molecular-weight heparin) and unfractionated heparin--versus enoxaparin alone on the recurrence of ischemia. BACKGROUND: Blocking some key factors of the coagulation cascade supports the concept that an antithrombin effect is needed during the acute phase of ischemia. METHODS: This was a prospective, randomized, pilot trial in patients with an acute coronary ischemic event occurring within the previous 24 hours. A total of 126 patients were allocated to receive aspirin (200 mg/day orally) plus 1 mg/kg subcutaneous enoxaparin at 8 AM and 12.500 IU of subcutaneous unfractionated heparin at 8 PM (group A) or subcutaneous enoxaparin 1 mg/kg (group B). RESULTS: Severe recurrent ischemia provoking urgent coronary revascularization occurred in 12 patients (9.5%), 3 (5%) in group A and 9 (13%) in group B (P = .1). Refractory angina was present in 27 patients (21%), 10 (17%) in group A and 17 (25%) in group B (P = .45). The combination of severe recurrent ischemia and refractory angina occurred in 23% of group A, and 37% of group B (odds ratio 0.49; 95% confidence intervals, 0.21-1.15; P = .07). A total of 7 patients (5%) had acute nonfatal myocardial infarction develop, 3 (5%) in group A and 4 (6%) in group B. Two (1.6%) deaths were observed in the study, both in group B. The incidence of the double end point (death plus nonfatal myocardial infarction) was 5% in group A versus 9% in group B (P = .5) and the triple end point (death, nonfatal myocardial infarction, and severe recurrent ischemia) was 10.5% in group A vs 22% in group B (odds ratio 0.42, 95% confidence intervals, 0.13-1.29; P = .09). CONCLUSIONS: The combination of 2 indirect antithrombin drugs capable of intermittently blocking the coagulation system is not associated with a significant loss of safety.
Assuntos
Anticoagulantes/uso terapêutico , Enoxaparina/uso terapêutico , Heparina/uso terapêutico , Isquemia Miocárdica/tratamento farmacológico , Isquemia Miocárdica/prevenção & controle , Doença Aguda , Angina Pectoris/epidemiologia , Angina Pectoris/etiologia , Angina Pectoris/fisiopatologia , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Aspirina/uso terapêutico , Quimioterapia Combinada , Enoxaparina/administração & dosagem , Enoxaparina/efeitos adversos , Feminino , Heparina/administração & dosagem , Heparina/efeitos adversos , Humanos , Incidência , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Mortalidade , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/etiologia , Isquemia Miocárdica/epidemiologia , Isquemia Miocárdica/fisiopatologia , Projetos Piloto , Prevenção Secundária , Índice de Gravidade de Doença , Método Simples-CegoRESUMO
BACKGROUND: This study was designed to analyze the impact of treatment with either unfractionated heparin or enoxaparin (low molecular weight heparin) on plasma markers of thrombotic and endogenous thrombolytic activity in patients with non-ST segment elevation acute coronary syndromes. METHODS: A subset of 174 patients derived from the 3,171 patients of the ESSENCE study was evaluated. Eighty-seven patients were assigned to intravenous unfractionated heparin (target aPTT: 55-85 sec) (group UH), and 87 assigned to subcutaneous enoxaparin (1 mg/kg/q12hr) (group ENOX) for a minimum of 48 hours of treatment (average duration of treatment 88+/-45 hours). The thrombin time, and plasma levels of anti-factor Xa activity, prothrombin fragment F 1+2, thrombin-antithrombin complex (TAT), and D-dimer, were assayed at baseline, and at or close to peak activity 24-36 hrs, and at 72-90 hrs for those remaining on treatment with antithrombotic therapy. Major ischemic and hemorrhagic events were assessed throughout hospitalization. The levels of the thrombotic markers measured at or close to peak activity at 36 hours are presented below, and compared to clinical outcome at 30 days. RESULTS: In UH patients, the thrombin time increased 7 fold while the mean value for anti-Xa activity was 0.27 IU/ml; in ENOX patients the thrombin time increased 2.3 fold, and the mean value for anti-Xa activity was 0.83 IU/ml. In UH pts, basal levels of F 1+2, TAT, and D-dimer declined by (deltapaired) -0.8, -3. 3, and -66, respectively. In ENOX pts, basal levels of F 1+2, TAT, and D-dimer declined by (deltapaired) -0.3, -4.7, and -23, respectively. No significant differences were observed between the paired differences in thrombotic markers (UH vs ENOX), nor in the rate of recurrent ischemic events or major hemorrhage. CONCLUSIONS: In this subset of patients enrolled in the ESSENCE study, enoxaparin 1 mg/kg ql2hr significantly increased anti-Xa activity above that seen with unfractionated heparin, and reduced thrombin production without prolonging the thrombin time. The high anti-Xa activity achieved with enoxaparin was not associated with a loss of safety.
Assuntos
Doença das Coronárias/tratamento farmacológico , Enoxaparina/uso terapêutico , Fibrinolíticos/uso terapêutico , Heparina/uso terapêutico , Biomarcadores , Doença das Coronárias/fisiopatologia , Método Duplo-Cego , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome , Resultado do TratamentoAssuntos
Ecocardiografia , Corpos Estranhos/diagnóstico , Traumatismos Cardíacos/diagnóstico , Coração/diagnóstico por imagem , Ferimentos por Arma de Fogo/diagnóstico , Adulto , Corpos Estranhos/diagnóstico por imagem , Traumatismos Cardíacos/diagnóstico por imagem , Humanos , Masculino , Radiografia , Ferimentos por Arma de Fogo/diagnóstico por imagemRESUMO
AIMS: Mounting evidence suggests infection, specifically Chlamydia pneumoniae, plays a role in atherosclerosis. We tested whether antibiotic treatment with the macrolide roxithromycin improves clinical outcome in patients with acute non-Q-wave coronary syndromes. Preliminary reports revealed a reduction in events in the roxithromycin group at 30 days. We now report the long-term follow-up results. METHODS AND RESULTS: Sixty-four per cent of the initial 202 patients with unstable angina who were randomly assigned to receive either roxithromycin or placebo for 30 days completed the active treatment period. At day 30, the primary triple and double end-point rates were 9% and 4% in the placebo group compared to 2% and 0% in the roxithromycin group (unadjusted P = 0.032 and 0.058, respectively). The secondary triple and double end-point rates were again higher in the placebo group at day 90 (12.5% and 6.25% vs 4.37% and 0%, unadjusted P = 0.065 and 0.029, respectively), and at day 180 (14.6% and 7.29% vs 8.69% and 2.17%, unadjusted P = 0.259 and 0.17, respectively). Anti-C, pneumoniae IgG titres were unchanged in both groups while C-reactive protein levels decreased in both strategies, with a more significant decrease in the roxithromycin arm (P = 0.03). Elevated C-reactive protein levels predicted the need for revascularization. CONCLUSIONS: In this pilot trial, roxithromycin appears to extend the clinical benefit of preventing death and re-infarction for at least 6 months after initial treatment.
Assuntos
Angina Instável/tratamento farmacológico , Antibacterianos/administração & dosagem , Roxitromicina/administração & dosagem , Idoso , Angina Instável/diagnóstico , Angina Instável/mortalidade , Angina Instável/fisiopatologia , Distribuição de Qui-Quadrado , Doença das Coronárias/diagnóstico , Doença das Coronárias/tratamento farmacológico , Doença das Coronárias/mortalidade , Doença das Coronárias/fisiopatologia , Eletrocardiografia/efeitos dos fármacos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Taxa de Sobrevida , Síndrome , Resultado do TratamentoRESUMO
Systemic serum markers of inflammation are elevated in diseases due to atherosclerosis, but have not been associated with the extent of atherosclerotic disease. We examined the role of neopterin, a byproduct of activated macrophage metabolism, in patients with unstable angina. Baseline neopterin samples and clinical histories were obtained in 52 patients admitted with unstable angina pectoris. Coronary angiograms of 27 patients were reviewed using Sullivan's method to assess the total atherosclerotic burden in the coronary arteries. Twenty-six of the 52 patients were eventually diagnosed with a non-Q-wave acute myocardial infarction (AMI) and had higher neopterin levels (10.1 +/- 6.7 vs 7.2 +/- 4.0 nmol/L, p = 0.06) than patients with a final diagnosis of unstable angina. Patients with neopterin >8.7 were more likely to be diagnosed with a non-Q-wave AMI (75% vs 39%, p = 0.035) and were more likely to have significantly more severe and extensive angiographically determined atherosclerosis than patients with low neopterin levels. Neopterin levels correlated with the score of atherosclerotic extension (Spearman's rank correlation coefficient 0.4807, p = 0.034). This study demonstrates a correlation between immune cell activation and the extent of angiographically determined atherosclerosis and the degree of myocardial ischemia.
Assuntos
Angina Instável/sangue , Angiografia Coronária , Doença da Artéria Coronariana/sangue , Infarto do Miocárdio/sangue , Neopterina/sangue , Idoso , Angina Instável/complicações , Angina Instável/diagnóstico por imagem , Biomarcadores/sangue , Doença da Artéria Coronariana/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico por imagemRESUMO
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.
Assuntos
Doença das Coronárias/tratamento farmacológico , Fibrinolíticos/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Aspirina/uso terapêutico , Quimioterapia Combinada , Humanos , Inibidores da Agregação Plaquetária/uso terapêutico , SíndromeRESUMO
BACKGROUND: There is serological evidence for an association between Chlamydia pneumoniae and coronary heart disease. We investigated the hypothesis that an antichlamydial macrolide antibiotic, roxithromycin, can prevent or reduce recurrent major ischaemic events in patients with unstable angina. METHODS: The effect of roxithromycin was assessed in a double-blind, randomised, prospective, multicentre, parallel-group, placebo-controlled pilot study of 202 patients with unstable angina or non-Q-wave myocardial infarction. Patients were randomly assigned either roxithromycin 150 mg orally twice a day (n = 102) or placebo orally twice a day (n = 100). The treatment was for 30 days. Patients were followed up for 6 months. We report the primary clinical endpoints (cardiac ischaemic death, myocardial infarction, and severe recurrent ischaemia), assessed at day 31, in 202 patients on an intention-to-treat basis. FINDINGS: A statistically significant reduction in the primary composite triple endpoint rates was observed in the roxithromycin group: p = 0.032. The rate of severe recurrent ischaemia, myocardial infarction, and ischaemic death was 5.4%, 2.2%, and 2.2% in the placebo group and 1.1%, 0%, and 0%, in the roxithromycin group, respectively. No major drug-related adverse effects were observed. INTERPRETATION: Antichlamydial antibiotics may be useful in therapeutic intervention in addition to standard medication in patients with coronary-artery disease. Large-scale trials are needed to confirm these preliminary observations.
Assuntos
Angina Instável/tratamento farmacológico , Antibacterianos/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Roxitromicina/uso terapêutico , Adulto , Idoso , Angina Instável/mortalidade , Angina Instável/prevenção & controle , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/prevenção & controle , RecidivaRESUMO
OBJECTIVES: Evidence exists showing an association between Chlamydial infection and infarction. Our purpose was to identify an interactive relationship between Chlamydia pneumoniae and unstable angina. METHODS: We analyzed IgG antibodies for Chlamydia pneumoniae, Mycoplasma pneumoniae, and C reactive protein in patients during the acute phase of unstable angina. RESULTS: Chlamydia antibodies were present in 16.92% (11 cases) of the unstable angina patients. They were also present in 34.61% of those patients who experienced ischemic events vs 5.1% who did not (odds ratio 9.79, 95% CL 1.65 to 75.26, p = 0.002). Mycoplasma pneumoniae antibodies were present in 12.30% of patients but did not emerge as a predictive variable. C-reactive protein was present in 22 cases (33.84%), 9 of which were associated with recurrent events (34.61%) vs 13 which were free of them (odds ratio, p = 0.5). The interactive relationship between infection plus C-reactive protein achieved a statistical significant association with ischemic events (odds ratio 14, 95% CI 1.49-331.1; p = 0.003). CONCLUSIONS: These findings suggest a pathophysiologically based relationship between infective and inflammatory processes related to poor clinical outcome during the in-hospital stay in the setting of unstable angina patients.
Assuntos
Angina Instável/sangue , Antígenos de Bactérias/sangue , Proteína C-Reativa/análise , Infecções por Chlamydia/imunologia , Chlamydophila pneumoniae/imunologia , Imunoglobulina G/sangue , Mycoplasma pneumoniae/imunologia , Pneumonia por Mycoplasma/imunologia , Angina Instável/imunologia , Angina Instável/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/etiologia , PrognósticoRESUMO
OBJECTIVES: This study was designed to test the hypothesis that low molecular weight heparin may lessen the severity of ischemic events in patients with unstable angina. BACKGROUND: Unstable angina is a thrombotic process that requires intensive medical treatment. Although current treatments can reduce the number of complications, serious bleeding continues to occur. Nadroparin calcium, a low molecular weight heparin, seems to be a safe therapeutic agent that does not require laboratory monitoring. METHODS: A total of 219 patients with unstable angina entered the study at a mean time of 6.17 h after the last episode of rest pain. Patients were randomized to receive aspirin (200 mg/day [group A]), aspirin plus regular heparin (400 IU/kg body weight per day intravenously and titered by activated partial thromboplastin time [group B]) and aspirin plus low molecular weight heparin (214 UIC/kg anti-Xa twice daily subcutaneously [group C]). The major end points determined for the in-hospital period were 1) recurrent angina, 2) myocardial infarction, 3) urgent revascularization, 4) major bleeding, and 5) death. Minor end points were 1) silent myocardial ischemia, and 2) minor bleeding. Event rates were tested by chi-square analysis. RESULTS: Recurrent angina occurred in 37%, 44% and 21% of patients in groups A, B and C, respectively, and was significantly less frequent in group C than in either group A (odds ratio 2.26, 95% confidence interval [CI] 1 to 5.18, p = 0.03) or group B (odds ratio, 3.07, 95% CI 1.36 to 7.00, p = 0.002). Nonfatal myocardial infarction was present in seven patients in group A, four in group B and none in group C (group B vs. A, p = 0.5; group C vs. A, p = 0.01). Urgent revascularization was performed in nine patients in group A, seven in group B and one in group C (C vs. A, p = 0.01). Two episodes of major bleeding occurred in group B. Silent myocardial ischemia was present in 38%, 41% and 25% of patients in groups A, B and C, respectively, and was significantly less frequent in group C than group B (odds ratio 2.12, 95% CI 0.97 to 4.69, p = 0.04). Minor bleeding was detected in 10 patients in group B, 1 patient in group C (B vs. C, p = 0.01) and no patient in group A (A vs. B, p = 0.003). CONCLUSIONS: In this study, treatment with aspirin plus a high dose of low molecular weight heparin during the acute phase of unstable angina was significantly better than treatment with aspirin alone or aspirin plus regular heparin.
Assuntos
Angina Instável/tratamento farmacológico , Aspirina/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Heparina/uso terapêutico , Isquemia Miocárdica/tratamento farmacológico , Adulto , Idoso , Angina Instável/prevenção & controle , Aspirina/efeitos adversos , Distribuição de Qui-Quadrado , Quimioterapia Combinada , Feminino , Hemorragia/induzido quimicamente , Heparina/efeitos adversos , Heparina de Baixo Peso Molecular/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/prevenção & controle , Isquemia Miocárdica/prevenção & controle , Razão de Chances , Estudos Prospectivos , Recidiva , Método Simples-Cego , Resultado do TratamentoRESUMO
Ischemic electrocardiographic changes were recorded within 2 hours of admission using a 12-lead electrocardiographic continuous monitor with a 20-second scanning interval and an alarm mode for asymptomatic events. Blood samples were obtained at admission and at the moment of asymptomatic events (group A). In the other patients who did not develop ischemia, a second blood sample was taken 12 hours later (group B). We determined prothrombin time, activated partial thromboplastin time, clotting factor VIII activity, tissue plasminogen activator activity, tissue plasminogen activator inhibitor-1, cross-linked fibrin degradation product, and thrombin-antithrombin III complexes. There was a statistically significant difference between group A and B patients when the basal samples were analyzed for thrombin-antithrombin III (p = 0.046) and d-Dimer (p = 0.005). Prothrombin fragment 1 + 2 were significantly reduced, and d-Dimer was elevated when basal blood samples were compared with the second sample in patients who developed silent events (p = 0.008 and 0.055, respectively). A plasma concentration of thrombin-antithrombin III complex was also significantly decreased when sample 2 was compared with the basal blood sample (p = 0.039). Five recurrent episodes of angina and 2 nonfatal infarctions occurred, and 4 urgent revascularization procedures were performed in group A. In group B, there was only 1 nonfatal infarction (p = 0.01). The results of the present study suggest that a time-dependent thrombotic process is detectable in the blood stream as a cyclic movement. Further studies are needed to determine if some other factors, such as intensive shear stress in the vessel wall, may activate plaque instability during asymptomatic episodes.
Assuntos
Angina Instável/sangue , Isquemia Miocárdica/sangue , Trombose/sangue , Doença Aguda , Idoso , Angina Instável/diagnóstico , Biomarcadores/sangue , Angiografia Coronária , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico , Isquemia Miocárdica/diagnóstico , Periodicidade , Prognóstico , Recidiva , Trombose/diagnósticoRESUMO
In this pilot study the combined use of desmopressin, which releases tissue plasminogen activator from vascular endothelium, and a low dose of streptokinase as a new thrombolytic regimen for acute myocardial infarction is proposed. Eighteen patients with acute myocardial infarction were treated intravenously with 150,000 U (4 patients) or 250,000 U (14 patients) of streptokinase infused over 10 minutes, followed by 24 µg of desmopressin infused over 5-10 minutes. Aspirin and beta-blockers were administered at admission, and heparin and oral anticoagulants were started at the end of the thrombolytic regimen. Hemostatic parameters were studied before and 30, 60, 120, and 240 minutes after starting thrombolytic therapy. Fifteen patients (83.3%) had evidence of clinical reperfusion. Angiography was performed with a mean delay of 8.8 hours (range 1.5-22 hours) from the start of thrombolytic therapy. Fourteen patients (77.8%) had patency of the infarct-related artery: 10 patients (55.6%) achieved TIMI grade 3, and 4 patients (22%) achieved TIMI grade 2. Two patients (one TIMI grade 1 and one TIMI grade 2) underwent coronary angioplasty. No patient died during the in-hospital period. At 18 months follow-up, all patients are alive. No major or minor bleeding was detected. The significant decline in plasma fibrinogen and in the euglobulin lysis time, and the increase in fibrinogen/fibrin degradation products, indicate a plasma lytic state. Crosslinked fibrin degradation products increased from 310 +/- 120 ng/ml to 670 +/- 310 ng/ml (p = 0.009), suggesting that fibrin digestion occurred in vivo. This pilot study provides data supporting the feasibility and efficacy of a new and more economic thrombolytic treatment of acute myocardial infarction without hemorrhagic complications.
RESUMO
The purpose of this study was to determine whether computerized ST-segment monitoring previous to percutaneous transluminal coronary angioplasty (PTCA) and after performance of this procedure may be useful to discern a pattern of recurrent angina. For this purpose, we analyzed 57 patients (11 women and 46 men, mean age 60 years) before and after treatment with balloon procedure. These patients were followed up during the next 3 months. A computerized electrocardiographic (ECG) device was used which was capable of recording simultaneously all 12 leads at rest. It was programmed to store a complete ECG every 5 min and was capable of detecting any abnormal ST alteration > than 0.5 mV at 80 ms after J junction, including R-wave amplitude. Measurements were started before (mean time 7.26 h) and after (mean time 7.96 h) the procedure. The value for ST amplitude at the J junction was used as the 0 point; then the most negative depression or the most positive elevation value was considered as the most abnormal ST alteration during monitoring. The patients were followed up for 3 months for the purpose of recognizing recurrent angina or establishing the occurrence of death. Twelve patients (30%) had recurrent angina. Discriminant function analysis revealed that ST monitoring in these patients showed significant difference after PTCA in comparison with controls, both in the frontal plane [ST depression 170 +/- 52 mV vs. 231 +/- 23 (p = 0.02)] and in precordial leads [176 +/- 16 vs. 80 +/- 6.19 mV (p = 0.0001)].(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Angina Pectoris/diagnóstico , Angioplastia Coronária com Balão , Diagnóstico por Computador , Eletrocardiografia/métodos , Adulto , Idoso , Angina Pectoris/fisiopatologia , Eletrocardiografia/instrumentação , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , RecidivaRESUMO
OBJECTIVE: To investigate whether plaque rupture and thrombosis have a role in silent ischaemia as well as in unstable angina. DESIGN: Prospective analysis of the results of haemostatic diagnostic tests at the moment of developing silent ischaemia at rest. SETTING: Coronary care unit. PATIENTS: 22 patients with acute myocardial infarction, 12 patients with symptomatic angina (unstable angina), and 10 normal volunteers (control group). INTERVENTIONS: Continuous cardiac monitoring detected 15 asymptomatic episodes (silent ischaemia) in 6 patients with unstable angina. Blood samples were obtained at admission and when an asymptomatic alteration was detected and 10 minutes later. MAIN OUTCOME MEASURES: Comparisons of concentrations of tissue plasminogen activator, urokinase type plasminogen activator, tissue plasminogen activator inhibitor-1, cross-linked fibrin degradation products, von Willebrand factor, and thrombin-antithrombin III complexes in patients and controls at admission; same comparisons in patients with silent ischaemia at the start of an episode and 10 minutes later. RESULTS: Tissue plasminogen activator concentrations were raised at admission in patients with acute myocardial infarction (mean (SD) 14.2 (6) ng/ml) and in patients with unstable angina (10.1 (2.5) ng/ml) in comparison with controls (5.1 (2.7) ng/ml, p < 0.01 and < 0.05 respectively). There was no differences between the two groups of patients, however. Similar results were observed at the start of a silent ischaemic episode (9.8 (1.9) ng/ml) and 10 minutes later (10.5 (2.9) ng/ml) compared with controls (p < 0.05). Tissue plasminogen activator inhibitor-1 concentrations were raised in patients with acute myocardial infarction (45.1 (15) ng/ml) compared with volunteers (20.6 (16) ng/ml, p < 0.01). In patients with silent ischaemia tissue plasminogen activator inhibitor-1 concentrations were slightly but not significantly increased. Concentrations of cross-linked fibrin degradation products (D dimer) increased during unstable angina (2150 (350) ng/ml) and silent ischaemia (2270 (450) ng/ml) compared with the concentrations in volunteers (340 (80) ng/ml) and patients with acute myocardial infarction (310 (120) ng/ml; p < 0.01). CONCLUSIONS: The results suggest that thrombosis mediates the pathophysiological mechanisms of silent ischaemia and unstable angina.
Assuntos
Angina Instável/etiologia , Infarto do Miocárdio/etiologia , Isquemia Miocárdica/etiologia , Trombose/complicações , Angina Instável/sangue , Eletrocardiografia Ambulatorial , Feminino , Fibrinólise/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Isquemia Miocárdica/sangue , Isquemia Miocárdica/diagnóstico , Inibidor 1 de Ativador de Plasminogênio/sangue , Estudos Prospectivos , Trombose/sangue , Ativador de Plasminogênio Tecidual/sangueRESUMO
This study was undertaken to determine whether prolonged QTc interval as a consequence of abnormal repolarization induced by coronary disease or antiarrhythmic drugs could be shortened by intravenous administration of magnesium sulfate. A total of 21 patients with basal prolonged QTc intervals (QTc > 500 ms) were divided in two groups: 7 with ischemic coronary disease and negative T waves (Group A), and 14 treated with antiarrhythmic drugs (Group B). Nine of the latter had negative T waves (Subgroup B-1) and five had positive T waves (Subgroup B-2) recorded in precordial leads. Nine patients were taking amiodarone and six quinidine. Magnesium sulfate was given intravenously in a bolus of 3.75 g (25% solution) over 3 min. Patients had normal electrolyte serum levels. The prolonged QTc and JTc intervals were shortened after magnesium sulfate in patients of Subgroup B-1 from the basal values [QTc 20.7% and JTc 25.4%, (p = < 0.0001 and 0.02, respectively)]. None of the patients in Group A or Subgroup B-2 experienced altered QTc or JTc intervals. While some antiarrhythmic drugs are capable of altering the refractoriness of ventricular cells, probably by causing changes in the intracellular metabolic pathways, in patients with coronary disease gaps in the membrane induced by ischemic injury let calcium enter the cells parallel with dispersion of ventricular repolarization. When secondary negative T waves are present, magnesium sulfate as an antidote probably acts as a blocking agent at the sarcoplasmic reticulum, thus reducing both QTc and JTc intervals.
Assuntos
Antiarrítmicos/efeitos adversos , Doença das Coronárias/fisiopatologia , Eletrocardiografia , Sulfato de Magnésio/uso terapêutico , Amiodarona/efeitos adversos , Amiodarona/antagonistas & inibidores , Feminino , Humanos , Sulfato de Magnésio/farmacologia , Masculino , Pessoa de Meia-Idade , Quinidina/efeitos adversos , Quinidina/antagonistas & inibidores , Retículo Sarcoplasmático/efeitos dos fármacosRESUMO
We studied the effects of intravenous flecainide acetate, given as a single dose of 2 mg/kg in no less than 15 minutes, on 31 patients with supraventricular tachyarrhythmias. Fourteen (87%) of the 16 patients with paroxysmal atrial fibrillation converted to sinus node rhythm. All 7 (100%) of the patients with paroxysmal supraventricular tachycardia converted to sinus node rhythm. Five (60%) of the 8 patients with paroxysmal atrial flutter converted to sinus node rhythm. The average time of conversion, after completion of drug administration, was 15 +/- 20 minutes. The QRS was prolonged an average of 82 to 91 milliseconds; in those cases who converted, the PR interval duration was 180 milliseconds average; QT was prolonged an average of 425-450 milliseconds. There were no changes in the JT interval, and we observed no hemodynamic untoward effects.