RESUMO
According to the Institute of Medicine (IOM) Committee on the Assessment of the U.S. Drug Safety System, "The recent highly publicized controversies surrounding the safety of some drugs have contributed to a public perception that the drug safety system is in crisis. It seems fair to say that this perception has created an opportunity for a thorough evaluation of the U.S. drug safety system." The evaluation was focused on the U.S. Food and Drug Administration (FDA). To improve the FDA and its function in the public health system to improve therapeutics, it is critical to understand the contributions of other components.
Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Disseminação de Informação/métodos , Informática em Saúde Pública/estatística & dados numéricos , Comportamento Cooperativo , Humanos , National Academies of Science, Engineering, and Medicine, U.S., Health and Medicine Division/organização & administração , Estados Unidos , United States Food and Drug Administration/organização & administraçãoRESUMO
AIMS: To evaluate the differential effects of eptifibatide therapy on unstable angina vs non-ST elevation myocardial infarction at enrollment, since the separate impact on these two major diagnostic subsets of acute coronary syndrome patients has not been fully investigated. METHODS AND RESULTS: We examined the 9461 patients in the PURSUIT trial (conducted between 1995 and 1997) to compare the effects of eptifibatide on unstable angina and myocardial infarction. The study showed greater and more consistent effects of eptifibatide therapy on unstable angina than non-ST elevation myocardial infarction in reducing 30-day death/(re)infarction (from the unadjusted rate of 13.0% to 11.2%, P=0.059 for unstable angina; and 18.9% to 17.9%, P=0.387 for myocardial infarction), especially among patients who underwent early percutaneous coronary intervention (odds ratios=0.49 and 0.86, 95% confidence intervals=0.30-0.80 and 0.53-1.42, respectively, for unstable angina and myocardial infarction). The only subgroup for whom the benefit of eptifibatide was not evident was female myocardial infarction patients who did not undergo early percutaneous coronary intervention. CONCLUSIONS: These data suggest that eptifibatide benefited unstable angina patients more than myocardial infarction patients, especially among those who underwent early percutaneous coronary intervention, and support its use as concomitant therapy with early percutaneous coronary intervention especially in female myocardial infarction patients.
Assuntos
Angina Instável/diagnóstico , Angina Instável/tratamento farmacológico , Eletrocardiografia , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/tratamento farmacológico , Peptídeos/administração & dosagem , Adulto , Fatores Etários , Idoso , Angina Instável/mortalidade , Eptifibatida , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Inibidores da Agregação Plaquetária/administração & dosagem , Probabilidade , Prognóstico , Modelos de Riscos Proporcionais , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Fatores Sexuais , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: Although severe chronic kidney disease (CKD) is an independent predictor of mortality among patients with coronary artery disease, the impact of mild CKD on morbidity and mortality has not been fully defined. METHODS AND RESULTS: Morbidity and mortality for the 3608 patients with multivessel coronary artery disease enrolled in the Bypass Angioplasty Revascularization Investigation randomized trial and registry were compared on the basis of the presence and absence of CKD, defined as a preprocedure serum creatinine level of >1.5 mg/dL. Seventy-six patients had CKD. Patients with renal insufficiency were older and more likely to have a history of diabetes, hypertension, and other comorbidities. Among patients undergoing PTCA, patients with CKD had a greater frequency of in-hospital death and cardiogenic shock (P<0.05 and 0.01, respectively). There was a trend toward a larger proportion of patients with CKD experiencing angina at 5 years (P=0.079). Patients with CKD had more cardiac admissions (P=0.003 and <0.0001 for patients undergoing PTCA and CABG, respectively) and a shorter time to subsequent CABG after initial revascularization than patients without CKD (P=0.01). CKD was associated with a higher risk of death at 7 years, both of all causes (relative risk 2.2, P<0.001) and of cardiac causes (relative risk 2.8, P<0.001). CONCLUSIONS: CKD is associated with an increased risk of recurrent hospitalization, subsequent CABG, and mortality. This increased risk of death is independent of and additive to the risk associated with diabetes.
Assuntos
Angioplastia Coronária com Balão , Ponte de Artéria Coronária , Doença da Artéria Coronariana/complicações , Falência Renal Crônica/complicações , Revascularização Miocárdica , Angina Pectoris/etiologia , Angioplastia Coronária com Balão/efeitos adversos , Ponte de Artéria Coronária/efeitos adversos , Doença da Artéria Coronariana/cirurgia , Creatinina/sangue , Complicações do Diabetes , Feminino , Seguimentos , Hospitalização/estatística & dados numéricos , Humanos , Falência Renal Crônica/sangue , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Modelos de Riscos Proporcionais , Recidiva , Reoperação/estatística & dados numéricos , Risco , Medição de Risco , Fatores de Risco , Taxa de SobrevidaRESUMO
BACKGROUND: Many patients with acute coronary syndromes are offered percutaneous coronary intervention. However, the appropriate indications for, and optimal timing of, such procedures are uncertain. We analysed timing of intervention and associated events (death and myocardial infarction) in the PURSUIT trial in which 9461 patients received a platelet glycoprotein IIb/IIIa inhibitor, eptifibatide, or placebo for 72 h. Other treatment was left to the investigators. 2430 patients underwent percutaneous coronary intervention within 30 days. Four groups were distinguished, who underwent percutaneous coronary intervention on day 1; on days 2 or 3; at 4 to 7 days; or between 8 until 30 days, for eptifibatide- and placebo-treated patients. RESULTS: The four groups treated with placebo demonstrated total 30-day events of 15.9% for day 1 percutaneous coronary intervention, 17.7%, 15.0% and 18.2%, respectively, for successive intervals of later intervention. Later intervention was associated with more pre-procedural events (2.2% to 13.7%, P=0.001) which was balanced by a decrease in procedure-related events (12.1 to 3.1%, P=0.001), while the overall 30-day event rates were similar. Eptifibatide-treated patients with percutaneous coronary intervention on day 1 had the lowest rate of 30-day events (9.2%, P<0.05 vs other groups). In this group, pre-procedural risk was only 0.3%, while percutaneous coronary intervention on eptifibatide treatment was associated with low procedural risk (7.2%). The total 30-day event rate for later percutaneous coronary intervention in patients receiving eptifibatide was 14.0 on days 2 and 3, 15.0% for days 4 to 7 and 17.4% for days 7 to 30, respectively. CONCLUSION: Patients treated with a platelet glycoprotein IIb/IIIa receptor blocker, and early percutaneous coronary intervention (within 24 h) had the lowest event rate in this post hoc analysis. Thus 'watchful waiting' may not be the optimal strategy. Rather an early invasive strategy with percutaneous coronary intervention under protection of a platelet glycoprotein IIb/IIIa receptor blocker should be considered in selected patients. Randomized trials are warranted to verify this issue.
Assuntos
Angioplastia Coronária com Balão , Doença das Coronárias/terapia , Eletrocardiografia , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/uso terapêutico , Complexo Glicoproteico GPIb-IX de Plaquetas/antagonistas & inibidores , Complexo Glicoproteico GPIb-IX de Plaquetas/uso terapêutico , Glicoproteínas da Membrana de Plaquetas , Doença Aguda , Terapia Combinada , Doença das Coronárias/complicações , Doença das Coronárias/mortalidade , Determinação de Ponto Final , Eptifibatida , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeos/antagonistas & inibidores , Peptídeos/uso terapêutico , Placebos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/mortalidade , Análise de Sobrevida , Síndrome , Fatores de Tempo , Resultado do TratamentoRESUMO
This study describes the dose-exploration phase of the PRIDE trial, an investigation of the clinical pharmacology of higher dose eptifibatide in patients who underwent elective percutaneous coronary intervention (PCI). Outcomes of treatment with the platelet glycoprotein IIb/IIIa inhibitors were dependent upon proper dosing selection. In this multicenter, placebo-controlled clinical study, 127 patients were randomized 1:1:2:2 into 1 of the following treatment groups: placebo; eptifibatide as a 135 microg/kg bolus followed by a 0.75 microg/kg/min infusion; eptifibatide as a 180 microg/kg bolus with a 2.0 microg/kg/min infusion; or eptifibatide as a 250 microg/kg bolus with a 3.0 microg/kg/min infusion. Light transmission aggregometry was used to determine platelet aggregation in response to 20 microM adenosine diphosphate, and platelet receptor occupancy was also determined. Eptifibatide exhibited linear pharmacokinetics over the dose range studied. Inhibition of platelet aggregation was greater in samples collected in sodium citrate compared with those collected in D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone. The 180/2.0 dosing regimen achieved 90% inhibition of platelet aggregation immediately (5 minutes) and at steady state (8 to 24 hours). At 1 hour, mean inhibition of platelet aggregation was 80%. Eptifibatide exhibited dose-dependent pharmacodynamics that were dependent upon choice of anticoagulant. A 180 microg/kg bolus followed by a 2.0 microg/kg/min infusion at steady state achieved >80% inhibition of platelet aggregation. With the single-bolus regimen, however, there was an early loss of the inhibition of platelet aggregation before steady state was reached. Additional dose-exploration studies may further optimize eptifibatide dosing.
Assuntos
Doença das Coronárias/terapia , Peptídeos/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Clorometilcetonas de Aminoácidos/farmacocinética , Angioplastia Coronária com Balão , Antitrombinas/farmacologia , Doença das Coronárias/mortalidade , Relação Dose-Resposta a Droga , Esquema de Medicação , Eptifibatida , Feminino , Humanos , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Peptídeos/administração & dosagem , Peptídeos/farmacocinética , Inibidores da Agregação Plaquetária/farmacocinéticaRESUMO
BACKGROUND: The segment of patients with advanced coronary artery disease, or disease that is not amenable to conventional revascularization therapies, continues to grow. Because the natural history of these patients is less defined, the appropriate end points for trials of novel revascularization therapies involving patients with advanced coronary artery disease are not certain. METHODS AND RESULTS: The Mediators of Social Support Study (MOSS) prospectively followed up outcomes of long-term survival, quality of life, resource use, and costs for 1189 patients and compared outcomes of patients with advanced coronary artery disease with those of a reference group who underwent bypass surgery or angioplasty. CONCLUSIONS: Despite greater disease burden, cost, and mortality for patients with advanced coronary artery disease, a number of self-reported measures of general health status improved in a similar fashion to that of patients eligible for angioplasty or bypass surgery. These findings should inform the design of trials involving novel therapies, suggesting that angina status and mortality be included as primary end points in the consideration of efficacy. This work also suggests that additional studies of novel therapies involving larger sample sizes may be required to confidently characterize efficacy.
Assuntos
Ensaios Clínicos como Assunto/métodos , Doença das Coronárias/diagnóstico , Cateterismo Cardíaco , Contraindicações , Doença das Coronárias/patologia , Doença das Coronárias/terapia , Vasos Coronários/patologia , Humanos , Revascularização Miocárdica , Prognóstico , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Trials report a 2% to 6% incidence of reinfarction after fibrinolysis for acute myocardial infarction (MI). We combined the Global Utilization of Streptokinase and Tissue plasminogen activator (alteplase) for Occluded coronary arteries (GUSTO I) and Global Use of Strategies To Open occluded coronary arteries (GUSTO III) populations to better define frequency, timing, and clinical predictors of in-hospital reinfarction. METHODS AND RESULTS: In 55 911 patients with ST-segment elevation myocardial infarction (MI) who were receiving fibrinolysis, we compared baseline characteristics and mortality rate by reinfarction incidence and developed multivariable logistic regression models to predict in-hospital reinfarction and composite of death or reinfarction. Reinfarction occurred in 2258 patients (4.3%) a median of 3.8 days after fibrinolysis; rates did not differ between GUSTO I (4.0%) and GUSTO III (4.2%) or by fibrinolytic assignment (streptokinase, 4.1%; alteplase, 4.3%; reteplase, 4.5%; combined streptokinase and alteplase, 4.4%; P=0.55). Advanced age, shorter time to fibrinolysis, non-US enrollment, nonsmoking status, prior MI or angina, female sex, anterior MI, and lower systolic blood pressure were associated significantly with reinfarction. Patients with reinfarction had higher mortality at 30 days (11.3% versus 3.5% without reinfarction; odds ratio, 3.5; P<0.001) and from 30 days to 1 year (4.7% versus 3.2%; hazard ratio, 1.5; P<0.001). Significant multivariate predictors of in-hospital death or reinfarction included age, Killip class, systolic and diastolic blood pressures, heart rate, anterior MI, smoking status, prior MI, sex, and country of enrollment (all P<0.001). CONCLUSIONS: Reinfarction occurs infrequently after fibrinolysis but confers increased risk of 30-day and 1-year mortality. Some predictors of reinfarction differ from known predictors of death after MI. Improved treatment and prevention strategies for reinfarction deserve study.
Assuntos
Fibrinólise , Infarto do Miocárdio/tratamento farmacológico , Idoso , Pressão Sanguínea/efeitos dos fármacos , Ensaios Clínicos como Assunto , Quimioterapia Combinada , Feminino , Fibrinolíticos/uso terapêutico , Frequência Cardíaca/efeitos dos fármacos , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/mortalidade , Recidiva , Estreptoquinase/uso terapêutico , Taxa de Sobrevida , Terapia Trombolítica , Fatores de Tempo , Ativador de Plasminogênio Tecidual/uso terapêutico , Resultado do TratamentoAssuntos
Fibrilação Atrial/etiologia , Fibrilação Atrial/mortalidade , Isquemia Miocárdica/complicações , Fibrilação Atrial/tratamento farmacológico , Método Duplo-Cego , Eptifibatida , Feminino , Humanos , Masculino , Isquemia Miocárdica/tratamento farmacológico , Peptídeos/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Modelos de Riscos Proporcionais , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/mortalidade , Análise de Sobrevida , Resultado do TratamentoRESUMO
Platelet glycoprotein IIb/IIIa inhibitors have been extensively studied in the treatment of patients with ischemic heart disease. Data regarding the use of these agents in the absence of concomitant intravenous heparin have been conflicting. We sought to determine, using propensity analysis, whether the benefit of eptifibatide, a IIb/IIIa inhibitor, in the treatment of acute coronary syndromes is affected by the concurrent administration of heparin. By trial design, patients were randomized to either eptifibatide or placebo, whereas use of intravenous heparin was left to the discretion of treating physicians. The effect of eptifibatide on the 30-day composite end point of death or myocardial infarction was studied in patients who received heparin and those who did not. Propensity analysis methods were used to control for confounding and presumed selection biases. Among 5,576 patients who were receiving heparin when the bolus dose of the study drug was administered, eptifibatide was associated with a reduced composite end point rate (13%) compared with that of placebo (14.5% vs 16.6%, p = 0.03). In contrast, among 1,441 patients who were not receiving heparin, there was no difference in 30-day event rates with eptifibatide compared with placebo (13.7% vs 13.1%, p > 0.7). After a propensity score for use of heparin was developed, however, use of heparin did not affect the reduced risk associated with eptifibatide (adjusted relative risk [RR] for heparin-eptifibatide interaction term 0.90, 95% confidence interval [CI] 0.61 to 1.32, p > 0.5), but the propensity for heparin use was a strong predictor of events (adjusted RR 1.76, 95% CI 1.42 to 2.17, p < 0.001). The use of eptifibatide independently predicted a lower risk of events (adjusted RR 0.31, 95% CI 0.10 to 0.93, p = 0.04). Thus, the apparent positive impact of heparin on the benefits of eptifibatide therapy was largely due to confounding and bias.
Assuntos
Angina Instável/tratamento farmacológico , Doença das Coronárias/tratamento farmacológico , Heparina/administração & dosagem , Infarto do Miocárdio/tratamento farmacológico , Peptídeos/administração & dosagem , Inibidores da Agregação Plaquetária/administração & dosagem , Idoso , Angina Instável/mortalidade , Viés , Doença das Coronárias/mortalidade , Relação Dose-Resposta a Droga , Método Duplo-Cego , Quimioterapia Combinada , Eptifibatida , Feminino , Heparina/efeitos adversos , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Peptídeos/efeitos adversos , Inibidores da Agregação Plaquetária/efeitos adversos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: Reliable predictors have yet to be found for recurrent ischemia after thrombolysis for acute myocardial infarction (AMI), nor do we know whether early angiography can herald recurrent ischemia. This study sought to investigate the relationship between recurrent ischemia and cardiac procedures after thrombolysis for AMI. METHODS: The Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) trial prospectively studied recurrent ischemia, which was defined as the presence of angina and changes in hemodynamics or the electrocardiogram. Cox regression analysis was used to identify predictors of recurrent ischemia. Other variables examined included time to coronary angiography and revascularization. RESULTS: Of 21,772 US GUSTO-I patients, 6313 (29%) had recurrent ischemia before discharge. Women (hazard ratio [HR] 1.25, 95% confidence interval [CI] 1.17-1.33) and patients with hypercholesterolemia (HR 1.14, 95% CI 1.07-1.22) or prior angina (HR 1.40, 95% CI 1.32-1.49) had a higher likelihood of recurrent ischemia. Current smoking and hours to thrombolysis were inversely related to recurrent ischemia (HR 0.86, 95% CI 0.81-0.92, HR 0.97, 95% CI 0.95- 0.99, respectively). Patients who underwent angiography before recurrent ischemia had a marginally increased risk of ischemia within 12 hours after angiography (HR 1.2, 95% CI 1.1-1.4); ultimately, they had a considerably lower risk 1 week after angiography than did patients without angiography (HR 0.57, 95% CI 0.45-0.72). CONCLUSIONS: Female sex, hypercholesterolemia, prior angina, and nonsmoking status weakly predict recurrent ischemia. Early coronary angiography reduces recurrent ischemia, probably because high-risk patients are identified and revascularized.
Assuntos
Infarto do Miocárdio/tratamento farmacológico , Isquemia Miocárdica/etiologia , Terapia Trombolítica , Cateterismo Cardíaco , Ensaios Clínicos como Assunto , Angiografia Coronária , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Recidiva , Fatores de TempoRESUMO
BACKGROUND: Although more than 9500 patients have been enrolled in major clinical trials in Latin America, practice patterns in this region have rarely been examined. We sought to compare characteristics, resource utilization, and outcomes of patients treated for acute coronary syndromes in Latin America with those in North America. METHODS: The Platelet IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Theraphy Trial (PURSUIT) enrolled 10,948 patients with non-ST-segment elevation acute coronary syndromes, including 585 in Latin America and 4358 in North America. We analyzed regional differences in patient groups, treatment patterns, and outcomes and used logistic regression analysis to identify association of enrollment region and survival. RESULTS: For patients in Latin America, the length of hospital stay was significantly longer (10 [7, 15] days vs 6 [4, 9], P <.001). Angiograms, angioplasty, and bypass surgery were significantly less common in Latin America (46.2%, 17.6%, and 11.3% vs 79.4%, 33.6%, and 19.4%, P <.001). Thirty-day death/myocardial infarction was not significantly higher, although mortality alone was significantly higher (6.8% vs 3.1%, P <.001). After adjustment for baseline characteristics, enrollment in Latin America remained an independent predictor for death at 30 days (odds ratio [OR] [95% confidence interval (CI)] 2.42 [1.60-3.67]) and persisted at 6 months (OR [95% CI] 2.5 [1.8-3.4]). CONCLUSIONS: Latin American patients treated for acute coronary syndromes were managed less invasively and were twice as likely as their North American counterparts to die within 6 months. This mortality difference was not explained by imbalances in baseline risk.
Assuntos
Angina Instável/tratamento farmacológico , Angina Instável/mortalidade , Peptídeos/uso terapêutico , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Padrões de Prática Médica , Eptifibatida , Feminino , Humanos , América Latina/epidemiologia , Tempo de Internação , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , América do Norte/epidemiologia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Patients with prior coronary bypass surgery with acute ST-segment elevation myocardial infarction (MI) pose an increasingly common clinical problem. We assessed the characteristics and outcomes of such patients undergoing thrombolysis for acute MI. METHODS AND RESULTS: We compared the characteristics and outcomes of patients in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries trial (GUSTO-I) who had had prior bypass (n = 1784, 4% of the population) with those without prior coronary artery bypass grafting (CABG), all of whom were randomized to receive one of four thrombolytic strategies. Patients with prior bypass were older with significantly more prior MI and angina. Overall, 30-day mortality was significantly higher in patients with prior bypass (10.7% vs 6.7% for no prior bypass, P <.001); these patients also had significantly more pulmonary edema, sustained hypotension, or cardiogenic shock. Patients with prior bypass showed a 12.5% relative reduction (95% confidence interval, 0% to 41.9%) in 30-day mortality with accelerated alteplase over the streptokinase monotherapies. In the 62% of patients with prior CABG who underwent coronary angiography, the infarct-related vessel was a native coronary artery in 61.9% and a bypass graft in 38.1% of cases. The Thrombolysis in Myocardial Infarction (TIMI) 3 flow rate was 30.5% for culprit native coronary arteries and 31.7% for culprit bypass grafts. Patients with prior bypass had more severe infarct-vessel stenoses (99% [90%, 100%] vs 90% [80%, 99%], P <.001). CONCLUSIONS: The 30-day mortality in patients with prior CABG was significantly higher than that for patients without prior CABG. As in the overall trial, these patients derived an incremental survival benefit from treatment with accelerated alteplase, but mortality remained high (16.7%) at 1 year. These results are at least partially explained by the higher baseline risk of these patients and by the lower rate of patency of the infarct-related artery.
Assuntos
Ponte de Artéria Coronária , Infarto do Miocárdio/tratamento farmacológico , Terapia Trombolítica , Angiografia Coronária , Feminino , Fibrinolíticos/uso terapêutico , Heparina/uso terapêutico , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Ensaios Clínicos Controlados Aleatórios como Assunto , Estreptoquinase/uso terapêutico , Terapia Trombolítica/efeitos adversos , Ativador de Plasminogênio Tecidual/uso terapêutico , Resultado do TratamentoRESUMO
OBJECTIVES: We aimed to evaluate the benefits of the glycoprotein (GP) IIb/IIIa antagonist, eptifibatide, after patients with acute coronary syndromes (ACS) were admitted to hospitals that approach revascularization for ACS through early transfer to tertiary referral centers. BACKGROUND: Across a variety of hospital settings, GP IIb/IIIa inhibition, after patients were admitted to the hospital for non-ST segment elevation ACS, is associated with a reduction in death or myocardial infarction (MI) before and during a percutaneous coronary intervention. METHODS: The outcomes of 429 patients from 153 sites in the Platelet glycoprotein IIb/IIIa in unstable angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial, who were transferred during study drug infusion ("transfer patients"), were compared with those of 1,987 patients who either remained in the hospital at those sites or were transferred after study drug termination ("nontransfer patients"). RESULTS: The baseline characteristics of transfer and nontransfer patients were similar. Patients receiving eptifibatide were transferred less frequently than those receiving placebo (16% vs. 20%, p = 0.014). Transfer patients underwent more procedures and experienced a greater 30-day incidence of death or MI, as compared with nontransfer patients (21% vs. 12%, p = 0.001). Eptifibatide was associated with a reduction in death or MI through 30 days, independent of transfer status (2.5% absolute reduction), as well as for those transferred (5.5% absolute reduction). CONCLUSIONS: For patients with ACS admitted to community hospitals, eptifibatide is associated with a reduced need for transfer and improved clinical outcomes.
Assuntos
Doença das Coronárias/tratamento farmacológico , Infarto do Miocárdio/tratamento farmacológico , Transferência de Pacientes , Peptídeos/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Idoso , Doença das Coronárias/mortalidade , Eptifibatida , Feminino , Hospitais Comunitários , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Revascularização Miocárdica , Peptídeos/efeitos adversos , Inibidores da Agregação Plaquetária/efeitos adversos , Encaminhamento e Consulta , Taxa de SobrevidaRESUMO
BACKGROUND: Early reinfarction after thrombolytic therapy is associated with adverse outcomes and increased mortality. Among patients with reinfarction in the 1992 Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO I) and the 1998 Assessment of the Safety of a New Thrombolytic (ASSENT 2) trials, we investigated temporal and regional differences in the use of repeat thrombolysis, revascularization (angioplasty and/or bypass surgery), or conservative measures and the outcomes of each management strategy. METHODS AND RESULTS: Data from the 4% of patients (n=2301) who experienced reinfarction after thrombolytic therapy were studied. Baseline characteristics, 30-day mortality, and incidence of total and hemorrhagic strokes were compared among the 3 treatment groups. The 30-day mortality did not differ between the repeat thrombolysis and revascularization groups (P=0.72), and it was significantly lower among patients treated by these 2 strategies than in those treated conservatively (11% and 11% versus 28%, respectively; P<0.001). Stroke rates did not differ significantly between the 3 treatment strategies (P=0.49). From 1992 to 1998, the percentage of reinfarction patients treated with repeat thrombolysis decreased from 29.3% to 18.5% in US centers and from 51.4% to 41.9% in all other centers (P<0.001). In contrast, use of revascularization procedures increased from 33.5% to 47.9% in US centers and from 8.1% to 23.0% in all other centers (P<0.001). CONCLUSIONS: Repeat thrombolysis and revascularization are associated with significantly lower mortality among reinfarction patients. Randomized trials are necessary to assess the exact risks and benefits of rethrombolysis versus interventional revascularization in this subset of high-risk patients presenting with reinfarction after thrombolytic therapy.
Assuntos
Doença das Coronárias/terapia , Infarto do Miocárdio/terapia , Estreptoquinase/uso terapêutico , Terapia Trombolítica/estatística & dados numéricos , Ativador de Plasminogênio Tecidual/uso terapêutico , Idoso , Angioplastia Coronária com Balão/estatística & dados numéricos , Ponte de Artéria Coronária/estatística & dados numéricos , Doença das Coronárias/complicações , Doença das Coronárias/prevenção & controle , Bases de Dados Factuais , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Análise Multivariada , Infarto do Miocárdio/etiologia , Estudos Retrospectivos , Fatores de Risco , Prevenção Secundária , Terapia Trombolítica/efeitos adversos , Terapia Trombolítica/métodos , Resultado do Tratamento , Estados UnidosRESUMO
Despite the deleterious and sometimes catastrophic consequences of proximal left anterior descending (LAD) artery occlusion, there is a paucity of data to guide the treatment of patients with such disease. Our aim was to describe outcomes with medical therapy, angioplasty, or left internal mammary artery (LIMA) bypass grafting in patients with 1-vessel, proximal LAD disease. We retrospectively analyzed prospectively collected data from 1,188 patients first presenting only with proximal LAD disease at 1 center over 9 years. We assessed the rates of death, acute myocardial infarction, and repeat intervention by initial treatment over a median 5.7 years of follow-up. Patients undergoing angioplasty or LIMA bypass were more often men and had progressive or unstable angina; those receiving medical therapy had a lower median ejection fraction. Both revascularization procedures offered slightly better adjusted survival versus medicine (hazard ratio for angioplasty, 0.82; 95% confidence interval, 0.60 to 1.11; hazard ratio for bypass, 0.74; 95% confidence interval, 0.44 to 1.23). Bypass, but not angioplasty, was associated with significantly fewer composite end point events (death, infarction, or reintervention, p <0.0001), and angioplasty was associated with a higher composite event rate than bypass or medical therapy (p <0.0001 and p = 0.0003, respectively). The initial advantages of bypass and medicine over angioplasty diminished over time; angioplasty became more advantageous than medicine after 1 year (p = 0.05) and not significantly different from bypass. Treatment of 1-vessel, proximal LAD disease with medicine, angioplasty, or UMA bypass resulted in comparable adjusted survival. However, LIMA bypass alone reduced the long-term incidence of infarctions and repeat procedures.
Assuntos
Angioplastia Coronária com Balão , Fármacos Cardiovasculares/uso terapêutico , Doença das Coronárias/terapia , Anastomose de Artéria Torácica Interna-Coronária , Idoso , Angina Instável/tratamento farmacológico , Angina Instável/cirurgia , Angina Instável/terapia , Baixo Débito Cardíaco/etiologia , Estudos de Coortes , Intervalos de Confiança , Doença das Coronárias/tratamento farmacológico , Doença das Coronárias/cirurgia , Progressão da Doença , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Razão de Chances , Modelos de Riscos Proporcionais , Estudos Prospectivos , Reoperação , Retratamento , Estudos Retrospectivos , Fatores Sexuais , Volume Sistólico , Taxa de Sobrevida , Resultado do TratamentoRESUMO
AIMS: We used the GUSTO-I and GUSTO-III databases to evaluate our performance in treating cardiogenic shock patients over much of the 1990s. METHODS AND RESULTS: GUSTO-I (1990-1993) and GUSTO-III (1995-1997) prospectively identified all patients with cardiogenic shock complicating acute myocardial infarction. Demographics, clinical presentation and outcomes for cardiogenic shock patients in the two trials were compared. Only patients enrolled with cardiogenic shock in countries common to both trials were included in these analysis. The 695 patients with cardiogenic shock in GUSTO-III were compared with the 2814 patients with cardiogenic shock in GUSTO-I. GUSTO-III patients were older (P=0.0001) and more likely to be diabetic (P=0.009) and hypertensive (P=0.025). They had a higher Killip class (P=0.002) and significantly greater index anterior infarction than cardiogenic shock patients enrolled in GUSTO-I. Time to treatment, presentation heart rate, and diastolic blood pressure were similar; however, systolic blood pressure at presentation was higher among GUSTO-III patients (P=0.002). Rates of coronary angiography, pulmonary artery catheterization, and mechanical ventilation declined in GUSTO-III compared with GUSTO-I (P=0.001); rates of angioplasty and bypass surgery were similar. Cardiogenic shock mortality in GUSTO-III was significantly higher than in GUSTO-I (62 vs 54%, P=0.001), as were rates of reinfarction (14 vs 11%, P=0.013) and recurrent ischaemia (35 vs 27%, P=0.00001). Mortality at non-U.S. sites (68 and 64%) was higher than at U.S. sites (53 and 50%) in both GUSTO-I and GUSTO-III studies, respectively. Angioplasty, bypass surgery, and balloon pump rates were lower for non-U.S. patients. CONCLUSIONS: Cardiogenic shock continues to be associated with high mortality in thrombolytic-treated patients. Lower mortality observed in the U.S.A. supports consideration for percutaneous and surgical revascularization.
Assuntos
Cardiologia/tendências , Revascularização Miocárdica , Choque Cardiogênico/mortalidade , Choque Cardiogênico/terapia , Terapia Trombolítica , Idoso , Austrália/epidemiologia , Canadá/epidemiologia , Bases de Dados Factuais , Europa (Continente)/epidemiologia , Feminino , Humanos , Incidência , Masculino , Análise Multivariada , Nova Zelândia/epidemiologia , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estados Unidos/epidemiologiaRESUMO
In 1994, the Agency for Health Care Policy and Research sponsored the development of guidelines for diagnosing and managing patients with unstable angina. Since their publication, several important developments have occurred. The prognostic value of biochemical assays for cardiac-specific troponins T and I have been shown in many studies. The possible role for C-reactive protein in determining prognosis deserves further investigation. Substantial clinical benefits have been obtained with intravenous inhibitors of the platelet glycoprotein (GP) IIb-IIIa receptor (abciximab, eptifibatide, tirofiban) and with one of the low-molecular-weight heparins (enoxaparin). The therapeutic potential of other low-molecular-weight heparins, direct thrombin inhibitors, and oral GP IIb-IIIa inhibitors remains to be clarified. On the basis of this evidence, consideration should be given to measuring serum levels of a cardiac troponin (either T or I) and using intravenous GP IIb-IIIa inhibitors and low-molecular-weight heparin in the standard management of patients with unstable angina.
Assuntos
Angina Instável/sangue , Angina Instável/tratamento farmacológico , Proteína C-Reativa/metabolismo , Heparina de Baixo Peso Molecular/uso terapêutico , Infarto do Miocárdio/prevenção & controle , Inibidores da Agregação Plaquetária/uso terapêutico , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Troponina I/sangue , Troponina T/sangue , Tirosina/análogos & derivados , Abciximab , Administração Oral , Angina Instável/complicações , Anticorpos Monoclonais/uso terapêutico , Diagnóstico Diferencial , Enoxaparina/uso terapêutico , Eptifibatida , Órgãos Governamentais , Heparina de Baixo Peso Molecular/administração & dosagem , Humanos , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Infusões Intravenosas , Infarto do Miocárdio/sangue , Infarto do Miocárdio/etiologia , National Institutes of Health (U.S.) , Peptídeos/uso terapêutico , Inibidores da Agregação Plaquetária/administração & dosagem , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/administração & dosagem , Guias de Prática Clínica como Assunto , Risco , Fatores de Tempo , Tirofibana , Tirosina/uso terapêutico , Estados UnidosRESUMO
BACKGROUND: Abciximab during percutaneous coronary revascularization reduces ischemic complications, but concern exists regarding increased bleeding risk should emergency coronary surgical procedures be required. METHODS: Outcomes were assessed among 85 patients who required coronary artery bypass grafting operations after coronary intervention in two randomized placebo-controlled trials of abciximab. Comparisons were made between patients in the pooled placebo and abciximab groups. RESULTS: The incidence of coronary surgical procedures was 2.17% and 1.28% among patients randomized to placebo and abciximab, respectively (p = 0.021). Platelet transfusions were administered to 32% and 52% of patients in the placebo and abciximab groups, respectively (p = 0.059). Rates of major blood loss were 79% and 88% in the placebo and abciximab groups, respectively (p = 0.27); transfusions of packed red blood cells or whole blood were administered in 74% and 80% of patients, respectively (p = 0.53). Surgical reexploration for bleeding was required in 3% and 12% of patients, respectively. Death and myocardial infarction tended to occur less frequently among patients who had received abciximab. CONCLUSIONS: Urgent coronary artery bypass grafting operations can be performed without an incremental increase in major hemorrhagic risk among patients on abciximab therapy.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Perda Sanguínea Cirúrgica , Ponte de Artéria Coronária , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Abciximab , Angioplastia Coronária com Balão , Tratamento de Emergência , Humanos , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , StentsRESUMO
BACKGROUND: A multinational, randomized, placebo-controlled trial (Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy, PURSUIT) demonstrated that the platelet glycoprotein IIb/IIIa receptor antagonist eptifibatide reduced the incidence of death or myocardial infarction among patients with acute ischemic syndromes without ST-segment elevation. Because of expected differences in practice patterns, a prospectively planned analysis of outcomes as a function of regions of the world was performed. The current study provides a detailed assessment of eptifibatide among the subgroup of patients enrolled within the United States. METHODS AND RESULTS: Patients presenting with chest pain within the previous 24 hours and ischemic ECG changes or creatine kinase-MB elevation were eligible for enrollment. Of the 10 948 patients randomized worldwide, 4035 were enrolled within the United States. Patients were allocated to placebo or eptifibatide infusion for up to 72 to 96 hours. Other medical therapies and revascularization strategies were at the discretion of the treating physician. Eptifibatide reduced the rate of the primary end point of death or myocardial infarction by 30 days from 15.4% to 11.9% (P=0.003) among patients in the United States. The treatment effect was achieved early and maintained over a period of 6 months (18.9% versus 15.2%; P=0.004). Bleeding events were more common in patients receiving eptifibatide but were predominantly associated with invasive procedures. The magnitude of clinical benefit from eptifibatide was greater among patients in the United States than elsewhere in the world. CONCLUSIONS: Platelet glycoprotein IIb/IIIa receptor blockade with eptifibatide reduces the incidence of death or myocardial infarction among patients treated for acute ischemic syndromes without ST-segment elevation within the United States.
Assuntos
Doença das Coronárias/tratamento farmacológico , Peptídeos/uso terapêutico , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Doença Aguda , Doença das Coronárias/epidemiologia , Eptifibatida , Hemorragia/complicações , Humanos , Inibidores da Agregação Plaquetária/uso terapêutico , Síndrome , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: A proportion of patients who present with suspected acute coronary syndrome (ACS) are found to have insignificant coronary artery disease (CAD) during coronary angiography, but these patients have not been well characterized. METHODS AND RESULTS: Of the 5767 patients with non-ST-segment elevation ACS who were enrolled in the Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin (Eptifibatide) Therapy (PURSUIT) trial and who underwent in-hospital angiography, 88% had significant CAD (any stenosis >50%), 6% had mild CAD (any stenosis >0% to =50%), and 6% had no CAD (no stenosis identified). The frequency of death or nonfatal myocardial infarction at 30 days was reduced with eptifibatide treatment in patients with significant CAD (18.3% versus 15.6% for placebo, P=0.006) but not in those with mild CAD (6.6% versus 5.4%, P=0.62) and with no CAD (3.0% versus 1. 2%, P=0.28). We identified independent baseline predictors of insignificant CAD (mild or no CAD) and used them to develop a simple predictive nomogram of the probability of insignificant CAD for use at hospital presentation. This nomogram was validated in a separate population of patients with non-ST-segment elevation ACS. CONCLUSIONS: Patients with suspected ACS found to have insignificant CAD have a low risk of adverse outcomes, do not appear to benefit from treatment with eptifibatide, and can be predicted with a simple nomogram drawn from baseline characteristics. Because patients with significant CAD appear to have an enhanced benefit from eptifibatide treatment, the predictive nomogram developed can be used to determine indications for glycoprotein IIb/IIIa blockade.