Health economic analysis of ticagrelor in patients with acute coronary syndromes intended for non-invasive therapy.

OBJECTIVE: To investigate the cost effectiveness of ticagrelor versus clopidogrel in patients with acute coronary syndromes (ACS) in the Platelet Inhibition and Patient Outcomes (PLATO) study who were scheduled for non-invasive management. METHODS: A previously developed cost effectiveness model was used to estimate long-term costs and outcomes for patients scheduled for non-invasive management. Healthcare costs, event rates and health-related quality of life under treatment with either ticagrelor or clopidogrel over 12 months were estimated from the PLATO study. Long-term costs and health outcomes were estimated based on data from PLATO and published literature sources. To investigate the importance of different healthcare cost structures and life expectancy for the results, the analysis was carried out from the perspectives of the Swedish, UK, German and Brazilian public healthcare systems. RESULTS: Ticagrelor was associated with lifetime quality-adjusted life-year (QALY) gains of 0.17 in Sweden, 0.16 in the UK, 0.17 in Germany and 0.13 in Brazil compared with generic clopidogrel, with increased healthcare costs of €467, €551, €739 and €574, respectively. The cost per QALY gained with ticagrelor was €2747, €3395, €4419 and €4471 from a Swedish, UK, German and Brazilian public healthcare system perspective, respectively. Probabilistic sensitivity analyses indicated that the cost per QALY gained with ticagrelor was below conventional threshold values of cost effectiveness with a high probability. CONCLUSIONS: Treatment of patients with ACS scheduled for 12 months' non-invasive management with ticagrelor is associated with a cost per QALY gained below conventional threshold values of cost effectiveness compared with generic clopidogrel. TRIAL REGISTRATION NUMBER: NCT000391872.

Early infarct artery collateral flow does not improve long-term survival following thrombolytic therapy for acute myocardial infarction.

It is known that acutely developed collaterals can prevent the onset of acute myocardial infarction (AMI) in the presence of a total coronary occlusion. However, there still is controversy concerning long-term follow-up of coronary collateral circulation to the infarct-related artery. In this study we analyze the prognostic role of collateral flow (degrees 0 to 3) as well as anterograde flow (degrees 0 to 3) in patients with AMI treated with thrombolytic therapy. Four hundred twenty-two patients (median age 57 years, 355 men) with AMI were treated with intravenous streptokinase and followed prospectively for up to 8 years. At the end of the study period, patients with collateral coronary flow 3 (n = 30) and those with flow <3 (n = 392) at in-hospital coronary arteriography had survival rates of 66% and 85%, respectively (p <0.12). Meanwhile, patients with coronary anterograde flow 3 (n = 189) and those with flow <3 (n = 233) had survival rates of 89% and 80%, respectively (p <0.04). By censored regression analysis, a negative correlation was found between coronary collateral flow degree and survival (p = 0.0498) and, inversely, a positive correlation was found between coronary anterograde flow degree and survival (p = 0.0053). By Cox multivariate analysis, the following variables showed significant correlations with long-term survival: global left ventricular ejection fraction (p = 0.0003), anterograde flow degree (p = 0.0006), collateral flow degree (negative correlation, p = 0.0179), and medical treatment (negative correlation, p = 0.0464). Thus, patients treated with intravenous streptokinase during AMI and with adequate coronary collateral circulation had a worse prognosis than those who developed adequate anterograde flow, probably because of residual myocardial ischemia. Such patients may benefit from coronary revascularization (angioplasty or surgery) to restore anterograde blood flow and minimize myocardium at risk.

Sinus bradycardia as a predictor of right coronary artery occlusion in patients with inferior myocardial infarction.

Differentiation of right coronary artery (RCA) from left circumflex artery (LCxA) occlusion may be difficult since both can present an electrocardiographic pattern of inferior myocardial infarction (IMI). We studied 133 patients with IMI, 92 patients with RCA occlusion and 41 patients with LCxA occlusion. Risk factors such as previous MI, arterial hypertension, diabetes, smoking, and dislipemia, were similar for RCA and LCxA occlusions. Patients with RCA occlusion had a higher incidence of isolated IMI than patients with LCxA occlusion, 50% vs. 17%, respectively (P<0.001). Arterial hypotension was more prevalent (P<0.05) among patients with RCA (18%) rather than those with LCxA occlusion (2%). RCA occlusion presented an association with sinus bradycardia, an association not observed with LCxA occlusion (15% vs. 0%, respectively; P<0.01). Total atrioventricular block was only present among patients with RCA (18%). Proximal occlusions of the RCA presented lower heart rates (sinus bradycardia) than medial and distal occlusions (13% vs. 1% and 1%, respectively; P<0.0001 and P<0.001). Therefore, regarding patients with IMI: (1) sinus bradycardia is more frequent when the infarct-related artery is the RCA; (2) proximal occlusions of the right coronary predispose low heart rates; and (3) occlusion of the LCxA rarely induces sinus bradycardia.

Arritmias no infarto agudo do miocárdio / Arrhythmias in acute myocardial infarction

Há alta incidência de arritmias no pós-infarto agudo do miocárdio. Distúrbios no ritmo e na condução estão entre as primeiras complicaçöes descritas. Embora eses distúrbios sejam claramente menos comuns em pacientes tratados com terapia fibrinolítica, permanecem uma contínua fonte de problemas para os clínicos que cuidam de pacientes com infarto agudo do miocárdio. Além disso, incertezas acerca da utilização de medidas terapêuticas, medidas profiláticas e prognóstico a curto e longo prazos têm estimulado a realização de vários estudos no sentido de definição de prognóstico a curto e longo prazos têm estimulado a realização de vários estudos no sentido de definição de prognóstico, prevenção e tratamento das arritmias no infarto agudo do miocárdio. Neste artigo, os autores abordam o manuseio clínico das arritmias no infarto agudo do miocárdio, com ênfase na incidência, no prognóstico, na prevenção e no tratamento.

Pheochromocytoma with echocardiographic features of obstructive hypertrophic cardiomyopathy. A case report.

The authors report a case of pheochromocytoma in which the echocardiographic features suggested obstructive hypertrophic cardiomyopathy. The angiographic study and the computed tomography showed the tumor and its arterial supply. One month after resection of the tumor the echocardiographic features showed a tendency to normalization. The preoperative echocardiographic aspect was probably due to excessive production of catecholamines by the tumor.

[Rupture of the left ventricular free wall. A lethal entity that can be surgically treated with success]. / Ruptura da parede livre do ventrículo esquerdo. Uma entidade letal que pode ser tratada cirurgicamente com sucesso.

We present three patients with left ventricular free wall rupture post acute myocardial infarction, all three treated successfully through surgery. Two of them were submitted to streptokinase IV. In all cases the diagnosis were based on clinical and echocardiographic features. The authors conclude that the diagnostic suspicion can be done easily, the echocardiogram is very useful, and the surgical treatment may led to a good short- and long-term survival.

Surgical revascularization after fibrinolysis in acute myocardial infarction. Long-term follow-up.

One hundred twenty-eight patients with myocardial infarction who underwent operation for myocardial revascularization and 147 patients who received medical therapy were followed up for up to 6 years: all patients had received treatment with intravenous streptokinase. In the surgical group, 91.5% of the patients had the region related to the infarction revascularized, and in 82.8% of them the mammary artery was used. Statistically significant differences were not detected between the groups according to infarct size, clinical features, and left ventricular ejection fraction. However, there was a higher risk in the surgical group, as compared with that in the medical group, in terms of anatomic characteristics: 99.2% versus 77.1% of the patients showed more than 70% residual obstruction at the "culprit" coronary artery (p < 0.001, 95% confidence interval 14.1% to 30.1%) and 76.8% versus 40.7% showed multivessel coronary disease (p < 0.001, 95% confidence interval 23.7% to 48.5%). In-hospital survival was 95.3% in the surgical group and 89.1% in the medical group (p = 0.096, 95% confidence interval -0.2% to 12.6%). Significantly higher survivals were obtained for the surgical group both during the first (93% +/- 2.3% versus 80.3% +/- 3.3%, p = 0.005) and the sixth (86.4% +/- 3.4% versus 68.4% +/- 4.3%, p = 0.003) year of follow-up. Statistically significant differences were also obtained when in-hospital deaths were excluded. A Cox regression model with 13 variables showed that only age (p = 0.0422) and medical treatment (p = 0.0194) correlated independently with mortality. It is concluded that in this nonrandomized study, operation led to a significantly higher survival both on a medium- and long-term basis, when compared with that obtained for patients receiving medical therapy.

[In-hospital survival predictors in infarction patients undergoing fibrinolytic therapy]. / Preditores da sobrevida intra-hospitalar em pacientes infartados submetidos à terapêutica fibrinolítica.

PURPOSE: To analyze the in-hospital predictors of survival in a population of infarcted patients submitted to the same therapeutic protocol that included IV streptokinase (SK) in the dose of 750,000 units. METHODS: Three hundred and thirty two patients (mean age 55.6 +/- 10 years, 82.3% men) with acute myocardial infarction (AMI) were studied within six hours of onset of symptoms in a prospective and consecutive protocol. Using simple and multiple regression analysis, the following variables were selected for correlation with survival: LV ejection fraction by contrast ventriculography > 50%; CK-MB peak < or = 100 UI/1; male sex; invasive treatment (surgery or angioplasty); patent "culprit" coronary on cineangiography; age < or = 65 years; time interval between the onset of pain and the beginning of SK infusion < 3 hours; residual obstruction < 70% at the "culprit" coronary; inferior AMI location on ECG; absence of hypotension per-peri SK infusion, previous AMI, multivessel coronary artery disease and reinfarction. RESULTS: By simple regression analysis, ejection fraction > 50% (p < 0.001), CK-MB peak < or = 100 UI/1 (p = 0.003), and the absence of hypotension (p < 0.001), previous AMI (p = 0.009), multivessel coronary artery disease (p = 0.02) and reinfarction (p = 0.049), correlated significantly with survival. By multiple regression analysis ejection fraction > 50% (p = 0.017) and the absence of hypotension (p < 0.01), multivessel coronary artery disease (p = 0.032) and reinfarction (p = 0.037) correlated independently with survival. CONCLUSION: The data presented strongly support the concept of preventing atherosclerosis and maintaining myocardial viability using either direct measures such as recanalization, or indirect measures such prevention of hypotension and reinfarction.

[Diagnosis and therapeutic follow-up of patients with massive pulmonary emboli by two-dimensional echocardiography]. / Diagnóstico e acompanhamento terapêtico de pacientes com embolia pulmonar maciça através da ecocardiografia bidimensional.

PURPOSE: The aim of the study was to analyse the role of 2D echocardiogram (ECHO) in the diagnosis of massive pulmonary embolism (PE), and in the follow-up after fibrinolytic or surgical treatment. METHODS: Echocardiographic studies were retrospectively analysed in seven patients, 5 male, mean age 37 +/- 19 years, with massive pulmonary embolism (PE) confirmed by pulmonary angiography. Six of them were submitted to fibrinolytic therapy with IV streptokinase (SK), and one underwent surgery. The diagnosis of PE by ECHO was made by the detection of thrombi in the pulmonary vascular bed. ECHO measurements included the right ventricular diastolic diameter (RVDD), interventricular septal motion (IVS), acceleration time (AcT), and peak pulmonary artery pressure (PAP). RESULTS: The ECHO study diagnosed thrombi in five out of seven patients (71%), mainly if they were present in the right main pulmonary artery (four cases -80%). It was also able to locate one out of five patients with thrombus in the right lobar artery and one out of two patients in the left main pulmonary artery; it was unable to identify six patients with involvement of the left lobar arteries. Four out of five patients with PE, diagnosed by ECHO, were submitted to fibrinolytic therapy, and one underwent surgery. The follow-up study showed dissolution of the thrombus in three of those with SK and in the one with surgical treatment. The initial ECHO study showed five out of 7 patients with increased RVDD, 5/7 patients with abnormal IVS motion, and all of them with decreased AcT (64 +/- 16 ms). The PSP was 64.4 +/- 22.8 mmHg by ECHO, versus 75.4 +/- 24.03 mmHg by angiography (r = 0.78; p = 0.11). There was a reduction of the RVDD (30 +/- 5.02 to 23 +/- 2.2) and an increased of the AcT (50 +/- 10.8 to 106.67 +/- 16) at the serial examination. CONCLUSION: The ECHO study is an important tool for the diagnosis of PE, informing about pulmonary pressure, presence and position of thrombus, and treatment results.

Acute myocardial infarction treated with intravenous streptokinase: 6-year follow-up.

Our objective was to investigate variables which, although occurring during the acute period, could influence the medium (1st year) and long-term (6th year) survival of infarcted patients. Of a total of 332 patients treated consecutively and prospectively according to the same protocol which included intravenous streptokinase, 305 survived the hospital phase and represent the study population. Mean patient age was 55.6 +/- 10 years and mean follow-up time was 3.33 years, with 1008.59 patient-years. The clinical course of the group was analyzed according to the following variables: left ventricle ejection fraction, hypotension per/peri streptokinase infusion, CK-MB peak, previous myocardial infarction, number of obstructed coronaries, reinfarction, sex, 'definitive' treatment, residual obstruction, age, pain/streptokinase infusion interval, patency of the 'culprit' coronary and infarct location. Overall, patient survival was 93.8 +/- 1.4% during the 1st year and 83.7 +/- 2.6% at the 6th. The following groups showed significantly different (log-rank) survivals: (a) 1st year: 94.6% for absence and 82.6% for presence of reinfarction (P = 0.0451); 97.9% for inferior and 91.4% for anterior infarct location (P = 0.044); 96.4% for ejection fraction > 50% and 90.6% for ejection fraction < or = 50% (P = 0.0187); 96.5% for angioplasty/surgery and 90.1% for clinical treatment (P = 0.0028); 95.5% for absence and 80.6% for presence of previous infarct (P = 0.0001). (b) 6th year: 88.3% for ejection fraction > 50% and 73.9% for ejection fraction < or = 50% (P = 0.028); 87.4% for < or = 65 and 66.4% for > 65 years (P = 0.0114); 89.6% for aggressive and 76.8% for conservative treatment (P = 0.013); 86.6% for absence and 60.7% for presence of previous infarct (P = 0.0009).

[Survival and predictive factors of late mortality in the surgical treatment of aortic stenosis]. / Sobrevida e fatores preditivos da mortalidade tardia no tratamento cirúrgico da estenose aórtica.

PURPOSE: Study of 161 patients submitted to aortic valve replacement due to aortic stenosis to evaluate survival and predictive factors of late mortality. METHODS: The mean age was 45.8 years +/- 13.2 and 122 patients were men. Surgical mortality was 6.8%. The survival actuarial curve showed 59.28% of the patients alive after 16 years. Among the survival 62.3% +/- 10% were event free, including prosthesis thrombosis, thromboembolism, infective endocarditis and reoperation. Symptoms, age, gradient LV/Ao, ejection fraction (EF) and the compliance (CO) were related to prognosis. Sudden death after surgery was studied, with incidence of the 0.8 events/100 patients year. RESULTS: The asymptomatic patients had better evolution than symptomatic (p less than 0.05). The age above 60 years was not predictive of the prognosis in 10 years of follow-up, but no patients survived after 10 years. The gradient LV/Ao was not an important factor in the survival. The group with EF greater than 50% had 66.4% of survival, while the group with EF less than 50% survival was 39%. Normal or decreased compliance was not important in the survival. All patients with EF less than 50% always has decreased CO. Fifteen patients were dead due to heart failure and the most important predictive factor was the left ventricular dysfunction (p = 0.02). CONCLUSION: In aortic stenosis: a) severe ventricular dysfunction does not preclude the surgical treatment; b) the actuarial analysis suggests that EF less than 50% determines worse prognosis and always occurs with decreased CO; c) the excellent evolution of the asymptomatic patients does not generalize the surgical treatment in this phase; d) the incidence of the sudden death was not high after the surgical treatment; e) patients with pre-operative left ventricular dysfunction had greater mortality due to heart failure, than patients with normal left ventricular function; f) despite of the morbid events our results confirm the real benefit of the surgical treatment in the aortic stenosis.

[Fibrinolytic therapy in non-coronary diseases]. / Terapêutica fibrinolítica em doenças não coronarianas.

Utilization of fibrinolytic drugs in non-coronary diseases has been described since 1949, but despite of that, works about that subject are very rare in the literature. In this paper we discuss the cases of three patients that were treated with such compounds for pulmonary embolism, peripheral arterial embolism, and thrombosis in mechanical aortic prosthesis. All patients had excellent in-hospital outcome, and were totally asymptomatic at the discharge time. It is emphasized the clinical symptoms, sometimes unexpected, and the importance of the complementary tests not only in the disease's diagnosis, but also in some decisions that must be taken during the patient's evolution, where they can help us to decide, for example, about the correct moment to stop the thrombolytic infusion. In conclusion, fibrinolytic drugs can be utilized in the management of many affections that otherwise would be treated by emergency surgery.

Acompanhamento de 991 pacientes portadores de marcapasso cardíaco artificial multiprogramável / Follow-up of 991 patients with multiprogrammable artificial cardiac pacemaker

É mostrada a experiência dos últimos 5 anos com o implante de 991 marcapassos cardíacos artificiais multiprogramáveis (66,1%) em pacientes portadores de miocardiopatia chagásica crônica) em freqüência de estimulaçäo, largura e amplitude de pulso, sensibilidade, período refratário e histerese. Em 684 pacientes (69%) houve necessidade de reprogramaçöes, na freqüência de estimulaçäo cardíaca artificial (27,9%), na largura e amplitude de pulso (46,5%), na sensibilidade 12,9%) e no período refratário e histerese (12,4%) neste período de acompanhamento. A multiprogramabilidade mostrou vantagens neste grupo de pacientes, principalmente em pacientes chagásicos, com complexos ventriculares aberrantes e, através de manobras näo-invasivas, evitou que 11,7% destes pacientes fossem reoperados