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.

Availability of on-site catheterization and clinical outcomes in patients receiving fibrinolysis for ST-elevation myocardial infarction.

AIMS: To compare management and clinical outcomes in hospitals stratified by the availability of on-site catheterization in InTIME-II, a multicentre trial comparing alteplase with lanoteplase for acute myocardial infarction. METHODS AND RESULTS: We studied 15,078 patients enrolled in 35 countries and 855 hospitals. Thirty-one percent of hospitals had 24-h, 25% day-only, and 44% no on-site catheterization facilities. Rates of cardiac angiography (57%, 38%, 26%) and revascularization (37%, 21%, 17%) were higher in hospitals with increasing access to on-site facilities(P<0.0001). The presence of a 24-h on-site facility was the strongest predictor of angiography during the index admission (odds ratio 4.17, 95% CI 3.85-4.54). There were no major differences in patient outcomes at 30 days when hospitals were stratified by availability of on-site catheterization. Adjusted 1-year mortality was similar between groups of hospitals (odds ratio for day-only 0.94 [0.80-1.09] and odds ratio for no availability 0.95 [0.83-1.10] compared to hospitals with 24-h facilities). CONCLUSIONS: There is a marked variation in procedure use by the availability of on-site catheterization with no major differences in patient outcomes. There is a need for additional randomized trials in the current era to address both the appropriate selection of patients and timing of invasive procedures in ST-elevation acute myocardial infarction.

Prognosis of acute myocardial infarction in the thrombolytic era: medical evaluation is still valuable.

BACKGROUND: Modern and sophisticated technology for the management of myocardial infarction has progressively devalued medical evaluation. HYPOTHESIS: This study was undertaken to assess the importance of the findings of medical evaluation at hospital presentation, in patients with acute myocardial infarction. METHODS: Data from 590 thrombolytic-treated myocardial infarction patients were analyzed. The patients were grouped according to their clinical status on arrival at hospital. A modified Forrester classification--subset II was divided according to the absence (IIa) or presence (IIb) of symptoms--was applied. Short- (14 days) and long-term (up to 10 years) survival was analyzed and 19 independent variables were included in the multivariate models. RESULTS: Short-term survival was 95.6% for subset I, 83.3% for subset IIa, 60% for subset IIb, 54.6% for subset III, and 34.8% for subset IV (P<0.001). By multiple regression analysis, lower clinical subsets (P<0.001), fewer coronary arteries with disease (P=0.006), younger age (P=0.014), absence of reinfarction (P=0.034), longer interval between streptokinase infusion and coronary arteriography (P=0.016), and higher left ventricular ejection fraction (P=0.037) demonstrated significant and independent correlation with short-term survival. Long-term survival for the total population was 71+/-3.6% for subset I, 54.4+/-8.5% for subset IIa, 20.8+/-9.4% for subset IIb, 54.5+/-15% for subset III, and 0% for subset IV (P<0.001). Using Cox regression analysis, lower clinical subsets (P<0.001), younger age (P<0.001), higher global left ventricular ejection fraction (P<0.001), and fewer coronary arteries with disease (P=0.021) correlated independently and significantly with long-term survival. When excluding data from patients who died before the short-term follow-up (n=532), lower clinical subsets remained an important predictor of long-term survival (P<0.001). CONCLUSION: Clinical classification at hospital presentation is a powerful predictor of short- and long-term survival post-myocardial infarction.

PANDORA - Survey of Brazilian cardiologists about cholesterol reduction.

OBJECTIVE: To report about a group of physicians' understanding of the recommendations of the II Brazilian Guidelines Conference on Dyslipidemias, and about the state of the art of primary and secondary prevention of atherosclerosis. METHODS: Through the use of a questionnaire on dyslipidemia, atherosclerosis prevention, and recommendations for lipid targets established by the II Brazilian Guidelines Conference on Dyslipidemias, 746 physicians, 98% cardiologists, were evaluated. RESULTS: Eighty-seven percent of the respondents stated that the treatment of dyslipidemia changes the natural history of coronary disease. Although most of the participants followed the total cholesterol recommendations (<200mg/dL for atherosclerosis prevention), only 55.8% would adopt the target of LDL-C <100 mg/dL for secondary prevention. Between 30.5 and 36.7% answered, in different questions, that the recommended level for HDL-C should be <35mg/dL. Only 32.7% would treat their patients indefinitely with lipid- lowering drugs. If the drug treatment did not reach the proposed target, only 35.5% would increase the dosage, and 29.4% would change the medication. Participants did not know the targets proposed for diabetics. CONCLUSION: Although the participating physicians valued the role played by lipids in the prevention of atherosclerosis, serious deficiencies exist in their knowledge of the recommendations given during the II Brazilian Guidelines Conference on Dyslipidemias.

Effect of cholesterol lowering treatment on positive exercise tests in patients with hypercholesterolaemia and normal coronary angiograms.

AIM: To assess the impact of cholesterol lowering on positive exercise stress tests in hypercholesterolaemic patients with normal coronary angiograms. METHODS: 43 non-diabetic patients aged 43-61 years, with total serum cholesterol concentrations of more than 7.75 mmol/l, positive exercise tests, and normal coronary angiograms, were started on the American Heart Association step 1 diet. After 12 weeks these patients were randomly assigned to treatment for another 16 weeks with the diet alone (diet group, n = 20) or with the diet plus lovastatin or simvastatin (statin group, n = 23). After this 28 week run in period, statins were withdrawn and lipid profile tests and exercise tests were done and repeated 20 weeks later. RESULTS: At week 28, the statin group but not the diet group had significant reductions from baseline (week 12) in plasma total cholesterol (p < 0.0001), low density lipoprotein (p < 0.0001), and triglyceride (p < 0.0001). The number of patients with positive exercise tests decreased from 23 to three in the statin group and from 20 to 15 in the diet group (p = 0.01). After the final 20 weeks without statins, lipid profiles returned to baseline levels in all 17 patients remaining in the statin group, and exercise tests were again positive in 15 of these patients. CONCLUSIONS: In hypercholesterolaemic patients with normal coronary arteries, cholesterol lowering treatment reduces myocardial ischaemia, as shown by the beneficial effects on exercise testing.

A multicenter, randomized study of argatroban versus heparin as adjunct to tissue plasminogen activator (TPA) in acute myocardial infarction: myocardial infarction with novastan and TPA (MINT) study.

OBJECTIVES: This study examined the effect of a small-molecule, direct thrombin inhibitor, argatroban, on reperfusion induced by tissue plasminogen activator (TPA) in patients with acute myocardial infarction (AMI). BACKGROUND: Thrombin plays a crucial role in thrombosis and thrombolysis. In vitro and in vivo studies have shown that argatroban has advantages over heparin for the inhibition of clot-bound thrombin and for the enhancement of thrombolysis with TPA. METHODS: One hundred and twenty-five patients with AMI within 6 h were randomized to heparin, low-dose argatroban or high-dose argatroban in addition to TPA. The primary end point was the rate of thrombolysis in myocardial infarction (TIMI) grade 3 flow at 90 min. RESULTS: TIMI grade 3 flow was achieved in 42.1% of heparin, 56.8% of low-dose argatroban (p = 0.20 vs. heparin) and 58.7% of high-dose argatroban patients (p = 0.13 vs. heparin). In patients presenting after 3 h, TIMI grade 3 flow was significantly more frequent in high-dose argatroban versus heparin patients: 57.1% versus 20.0% (p = 0.03 vs. heparin). Major bleeding was observed in 10.0% of heparin, and in 2.6% and 4.3% of low-dose and high-dose argatroban patients, respectively. The composite of death, recurrent myocardial infarction, cardiogenic shock or congestive heart failure, revascularization and recurrent ischemia at 30 days occurred in 37.5% of heparin, 32.0% of low-dose argatroban and 25.5% of high-dose argatroban patients (p = 0.23). CONCLUSIONS: Argatroban, as compared with heparin, appears to enhance reperfusion with TPA in patients with AMI, particularly in those patients with delayed presentation. The incidences of major bleeding and adverse clinical outcome were lower in the patients receiving argatroban.

Additional reduction in blood pressure after cholesterol-lowering treatment by statins (lovastatin or pravastatin) in hypercholesterolemic patients using angiotensin-converting enzyme inhibitors (enalapril or lisinopril).

Blood pressure (BP) reduction was compared between patients receiving angiotensin-converting enzyme inhibitors alone and patients receiving these medications plus statins after 3 months of dietary intervention. Although BP was similarly reduced at week 4, the statin-treated group had a greater reduction in BP and total cholesterol levels at week 16, suggesting a synergistic effect between cholesterol lowering with statins and angiotensin-converting enzyme inhibitor treatment for hypertensive patients.

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.

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.

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.

[Trends in cholesterol levels in the adult population of São José do Rio Preto]. / Evolução dos níveis de colesterol na população adulta de São José do Rio Preto (1991-1997).

PURPOSE: To develop a survey about risk factors for atherosclerosis in a > or = 20-year-old population from São José do Rio Preto, and compare the results with those obtained in a similar survey in 1991. METHODS: Quantitative survey with sample stratified by sex and age. The individuals (a total of 646, 303 men) where contacted in outpatient facilities from the Health Secretary and other populated sites, distributed by geographic zone and social class of different neighborhoods. The standard error of the survey was 4%, and the confidence interval was 95%. RESULTS: A) Mean HDL-cholesterol (only in 1997): male gender 43.7 +/- 15 mg/dL, female gender 49.6 +/- 13.5 mg/dL (p < 0.001, 95% CI 3.7 a 8.1). B) Mean total cholesterol in 1991 vs 1997: for the global population 192.5 +/- 48.9 mg/dL vs 190.5 +/- 42.5 mg/dL (p = NS); for men 187.6 +/- 53.3 mg/dL vs 190.5 +/- 42.5 mg/dL (p = NS); for women 196.8 +/- 40 mg/dL vs 187.6 +/- 37.8 mg/dL (p = 0.008, 95% CI 2.4 a 15.9). C) By regression analysis, the variables that correlated significantly with cholesterol levels, in both surveys, were: age (p < 0.001), systolic (p < 0.001) and diastolic (p < 0.001) arterial pressure, diet (p < 0.001). Female gender showed correlation only in the 1991 survey (p = 0.011), and sedentarism only in 1997 (p = 0.014). CONCLUSION: The mean cholesterol levels in the adult population of São José do Rio Preto are very favorable and, in female gender, showed a significant decrease in the 1997 survey, relatively to the 1991 survey.

The role of antegrade and collateral flow in relation to left ventricular function post-thrombolysis.

UNLABELLED: The aim of the study was to analyze the relationship between antegrade and collateral flow degree to the "culprit" coronary artery, and between both variables and left ventricular systolic function. We analyzed five hundred patients with acute myocardial infarction, treated prospectively and consecutively within 6 h of evolution with intravenous streptokinase. The degree of antegrade (0-3) and collateral blood flow (0-3) were correlated with 18 other variables. RESULTS: (a) By simple regression analysis, antegrade flow degree correlated positively (p < 0.0001), and collateral flow degree negatively (p = 0.0073) with left ventricular ejection fraction; (b) By multiple regression analysis, antegrade flow degree (p = 0.0032), but not collateral flow degree (p > 0.1), correlated independently with left ventricular ejection fraction; (c) In the subgroup of patients with occluded "culprit" coronary artery, the mean ejection fraction was significantly higher for those with collateral flow 3 (60.2% +/- 13.3 in relation to those with collateral flow < 3 (53.9% +/- 13.1, p = 0.032, 95% CI. 11.96 to (0.53%). In conclusion, antegrade coronary flow degree, but not collateral flow degree, correlated significantly and independently with left ventricular ejection fraction. However, in the subgroup of patients with occluded "culprit" coronary artery, collateral flow 3 led to better left ventricular systolic function, in relation to collateral flow < 3.

Diltiazem improves left ventricular systolic function following acute myocardial infarction treated with streptokinase. The Calcium Antagonist in Reperfusion Study (CARES) Group.

The role of diltiazem on left ventricular systolic function was analyzed in 101 patients with acute myocardial infarction treated with streptokinase, being obtained, for the total of the population, higher LV global ejection fraction (p = 0.022), LV regional shortening (p = 0.046) and LV global shortening (p = 0.064) for the treated group, relative to the placebo group; the p values were, respectively, 0.005, 0.009, and 0.012, for patients that achieved TIMI-3 antegrade coronary flow. It is concluded that diltiazem is useful as adjuvant to streptokinase, especially when antegrade coronary blood flow TIMI-3 is obtained.

[Left ventricular function in the acute phase of patients with myocardial infarction randomly treated with 750,000 or 1.5 million units of streptokinase]. / Função ventricular esquerda na fase aguda de infartados submetidos aleatoriamente a 750,000 ou 1.5 milhão de unidades de estreptoquinase.

PURPOSE: To compare the doses of 750,000 and 1.5 million units (U) of streptokinase (SK), relatively to the left ventricular (LV) systolic function analyzed through contrasted ventriculography. METHODS: We included 110 patients with acute myocardial infarction (AMI) within 6h of the onset (mean-age 60 years, 83.6% men), that were randomized to receive 750,000U of SK in 15 min (55 patients), or 1.5 million U in 30 min (55 patients). The study main goal was the comparison between the groups relatively to LV ejection fraction, global and regional shortening, obtained at the fifth day of the AMI. RESULTS: The 750,000 and 1.5 million groups were homogeneous relatively to 15 analyzed variables. Relatively to the main goal of the study, it was found respectively: a) ejection fraction analysis (median): 64% and 60.5% for the total population (p = 0.25, 95% CI -2.7 to 10), 64% and 57.5% for anterior AMI (p = 0.2, 95% CI -3.6 to 16.3), 65% and 65% for inferior AMI (p = 0.99, 95% CI -8.4 to 8.4); b) global shortening analysis: -2.53 and -2.66 for the total population (p = 0.3, 95% CI -0.47 to 0.87), -2.27 and -2.53 for anterior AMI (p = 0.18, 95% CI -0.3 to 1.4), -1.82 and 1.72 for inferior AMI (p = 0.9, 95% CI -0.82 to 0.75); c) regional shortening analysis: anterior AMI -2.6 and -2.67 (p = 0.47, 95% CI -0.7 to 1.5), inferior AMI -2.3 and -2.32 (p = 0.9, 95% CI -0.82 to 0.75). CONCLUSION: The dose of 750,000U was as efficacious as the 1.5 million relatively to LV systolic function, one of the best survival predictors of short-medium and long-term survival post AMI.