In-hospital death in acute coronary syndrome was related to admission glucose in men but not in women

Background: Admission hyperglycaemia is associated with mortality in patients with acute coronary syndrome (ACS), but controversy exists whether hyperglycaemia uniformly affects both genders. We evaluated coronary risk factors, gender, hyperglycaemia and their effect on hospital mortality. Methods: 959 ACS patients (363 women and 596 men) were grouped based on glycaemia >= or < 200 mg/dL and gender: men with glucose < 200 mg/dL (menG-); women with glucose < 200 mg/dL (womenG-); men with glucose >= 200 mg/dL (menG+); and women with glucose >= 200 mg/dL (womenG+). A logistic regression analysis compared the relation between gender and glycaemia groups and death, adjusted for coronary risk factors and laboratory data. Results group: menG- had lower mortality than menG+ (OR = 0.172, IC95% 0.062-0.478), and womenG+ (OR = 0.275, IC95% 0.090-0.841); womenG- mortality was lower than menG+ (OR = 0.230, IC95% 0.074-0.717). No difference was found between menG+ vs womenG+ (p = 0.461), or womenG- vs womenG+ (p = 0.110). Age (OR = 1.067, IC95% 1.031-1.104), EF (OR = 0.942, IC95% 0.915-0.968), and serum creatinine (OR = 1.329, IC95% 1.128-1.566) were other independent factors related to in-hospital death. Conclusions: Death was greater in hyperglycemic men compared to lower blood glucose men and women groups, but there was no differences between women groups in respect to glycaemia after adjustment for coronary risk factors.

Clinical evolution of patients hospitalized due to the first episode of Acute Coronary Syndrome

AIM: to assess the clinical evolution of patients hospitalized due to the first episode of Acute Coronary Syndrome (ACS) according to its clinical manifestation. METHODS: data were collected from 234 patients, hospitalized between May 2006 and July 2009 due to the first episode of an ACS, by consulting their medical records. RESULTS: 234 patients were hospitalized, 140 (59.8%) due to Acute Myocardial Infarction (AMI). In the group with AMI, 19.3% presented complications, against 12.8% in the group with Unstable Angina (UA) (p=0.19). Angioplasty levels were higher among patients with AMI than with UA (p=0.02) and coronary artery bypass graft surgery was more frequent among UA patients (p=0.03). The majority (227; 97%) survived after the coronary event. Among the seven patients who died during the hospitalization, four had AMI (2.9%) and three UA (3.2%). CONCLUSIONS: A larger number of complications were found among infarction victims and the accomplishment of coronary artery bypass graft surgery differed between the groups.

Adaptive immunity is related to coronary artery disease severity after acute coronary syndrome in subjects with metabolic syndrome

Metabolic syndrome (MetS) is an inflammatory state associated with high coronary disease risk. Inflammation and adaptive immunity modulate atherosclerosis and plaque instability. We examined early changes in anti-oxidized lowdensity lipoprotein (LDL) (anti-oxLDL) autoantibodies (Abs) in patients with MetS after an acute coronary syndrome (ACS). Patients of both genders (n=116) with MetS were prospectively included after an acute yocardial infarction (MI) or hospitalization due to unstable angina. Anti-oxLDL Abs (IgG class) were assayed at baseline, three and six weeks after ACS. The severity of coronary disease was evaluated by the Gensini score. We observed a decrease in anti-oxLDL Abs titers (p<0.002 vs. baseline), mainly in males (p=0.01), in those under 65 y (p=0.03), and in subjects with Gensini score above median (p=0.04). In conclusion, early decrease in circulating anti-oxLDL Abs is associated with coronary disease severity among subjects with MetS.

Ticagrelor Versus Clopidogrel in Patients With Acute Coronary Syndromes and a History of Stroke or Transient Ischemic Attack

Background-Patients with acute coronary syndromes and history of stroke or transient ischemic attack (TIA) have an increased rate of recurrent cardiac events and intracranial hemorrhages. Methods and Results-We evaluated treatment effects of ticagrelor versus clopidogrel in patients with acute coronary syndrome with and without a history of prior stroke or TIA in the PLATelet inhibition and patient Outcomes (PLATO) trial. Of the 18 624 randomized patients, 1152 (6.2%) had a history of stroke or TIA. Such patients had higher rates of myocardial infarction (11.5% versus 6.0%), death (10.5% versus 4.9%), stroke (3.4% versus 1.2%), and intracranial bleeding (0.8% versus 0.2%) than patients without prior stroke or TIA. Among patients with a history of stroke or TIA, the reduction of the primary composite outcome and total mortality at 1 year with ticagrelor versus clopidogrel was consistent with the overall trial results: 19.0% versus 20.8% (hazard ratio, 0.87; 95% confidence interval, 0.66-1.13; interaction P=0.84) and 7.9% versus 13.0% (hazard ratio, 0.62; 95% confidence interval, 0.42-0.91). The overall PLATO-defined bleeding rates were similar: 14.6% versus 14.9% (hazard ratio, 0.99; 95% confidence interval, 0.71-1.37), and intracranial bleeding occurred infrequently (4 versus 4 cases, respectively). Conclusions-Patients with acute coronary syndrome with a prior history of ischemic stroke or TIA had higher rates of clinical outcomes than patients without prior stroke or TIA. However, the efficacy and bleeding results of ticagrelor in these high-risk patients were consistent with the overall trial population, with a favorable clinical net benefit and associated impact on mortality.

In Patients With Acute Myocardial Infarction, the Impact of Hyperglycemia as a Risk Factor for Mortality Is Not Homogeneous Across Age-Groups

OBJECTIVE To assess the impact of hyperglycemia in different age-groups of patients with acute myocardial infarction (AM I). RESEARCH DESIGN AND METHODS A total of 2,027 patients with AMI were categorized into one of five age-groups: <50 years (n = 301), >= 50 and <60 (n = 477),>= 60 and <70 (n = 545), >= 70 and <80 (n = 495), and years (n = 209). Hyperglycemia was defined as initial glucose >= 115 mg/dL. RESULTS The adjusted odds ratios for hyperglycemia predicting hospital mortality in groups 1-5 were, respectively, 7.57 (P = 0.004), 3.21 (P 0.046), 3.50 (P = 0.003), 3.20 (P < 0.001.), and 2.16 (P = 0.021). The adjusted P values for correlation between glucose level (as a continuous variable) and mortality were 0.007, <0.001, 0.043, <0.001, and 0.064. The areas under the ROC curves (AUCs) were 0.785, 0.709, 0.657, 0.648, and 0.613. The AUC in group 1 was significantly higher than those in groups 3-5. CONCLUSIONS The impact of hyperglycemia as a risk factor for hospital mortality in AMI is more pronounced in younger patients.

Thrombin-Receptor Antagonist Vorapaxar in Acute Coronary Syndromes

BACKGROUND Vorapaxar is a new oral protease-activated receptor 1 (PAR-1) antagonist that inhibits thrombin-induced platelet activation. METHODS In this multinational, double-blind, randomized trial, we compared vorapaxar with placebo in 12,944 patients who had acute coronary syndromes without ST-segment elevation. The primary end point was a composite of death from cardiovascular causes, myocardial infarction, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization. RESULTS Follow-up in the trial was terminated early after a safety review. After a median follow-up of 502 days (interquartile range, 349 to 667), the primary end point occurred in 1031 of 6473 patients receiving vorapaxar versus 1102 of 6471 patients receiving placebo (Kaplan-Meier 2-year rate, 18.5010 vs. 19.9%; hazard ratio, 0.92; 95% confidence interval [CI], 0.85 to 1.01; P=0.07). A composite of death from cardiovascular causes, myocardial infarction, or stroke occurred in 822 patients in the vorapaxar group versus 910 in the placebo group (14.7% and 16.4%, respectively; hazard ratio, 0.89; 95% CI, 0.81 to 0.98; P=0.02). Rates of moderate and severe bleeding were 7.2% in the vorapaxar group and 5.2% in the placebo group (hazard ratio, 1.35; 95% CI, 1.16 to 1.58; P<0.001). Intracranial hemorrhage rates were 1.1% and 0.2%, respectively (hazard ratio, 3.39; 95% CI, 1.78 to 6.45; P<0.001). Rates of nonhemorrhagic adverse events were similar in the two groups. CONCLUSIONS In patients with acute coronary syndromes, the addition of vorapaxar to standard therapy did not significantly reduce the primary composite end point but significantly increased the risk of major bleeding, including intracranial hemorrhage. (Funded by Merck; TRACER ClinicalTrials.gov number, NCT00527943.)

Prasugrel versus Clopidogrel for Acute Coronary Syndromes without Revascularization

Background The effect of intensified platelet inhibition for patients with unstable angina or myocardial infarction without ST-segment elevation who do not undergo revascularization has not been delineated. Methods In this double-blind, randomized trial, in a primary analysis involving 7243 patients under the age of 75 years receiving aspirin, we evaluated up to 30 months of treatment with prasugrel (10 mg daily) versus clopidogrel (75 mg daily). In a secondary analysis involving 2083 patients 75 years of age or older, we evaluated 5 mg of prasugrel versus 75 mg of clopidogrel. Results At a median follow-up of 17 months, the primary end point of death from cardiovascular causes, myocardial infarction, or stroke among patients under the age of 75 years occurred in 13.9% of the prasugrel group and 16.0% of the clopidogrel group (hazard ratio in the prasugrel group, 0.91; 95% confidence interval [CI], 0.79 to 1.05; P = 0.21). Similar results were observed in the overall population. The prespecified analysis of multiple recurrent ischemic events (all components of the primary end point) suggested a lower risk for prasugrel among patients under the age of 75 years (hazard ratio, 0.85; 95% CI, 0.72 to 1.00; P = 0.04). Rates of severe and intracranial bleeding were similar in the two groups in all age groups. There was no significant between-group difference in the frequency of nonhemorrhagic serious adverse events, except for a higher frequency of heart failure in the clopidogrel group. Conclusions Among patients with unstable angina or myocardial infarction without ST- segment elevation, prasugrel did not significantly reduce the frequency of the primary end point, as compared with clopidogrel, and similar risks of bleeding were observed. (Funded by Eli Lilly and Daiichi Sankyo; TRILOGY ACS ClinicalTrials.gov number, NCT00699998.)

Endovascular Treatment for Acute Aortic Syndrome

Background: The term "acute aortic syndrome" (AAS) includes conditions of high mortality, such as ruptured aneurysm, pseudoaneurysm and, aortic dissection. Open surgery for these cases has demonstrated unsatisfactory results, and endovascular treatment has become an excellent alternative. Methods: We performed a retrospective review of patients with AAS who underwent endovascular treatment in our emergency department from July 2009 to February 2011. They represent 64% (16 of 25) of all patients with AAS seen during this period. Results: Sixteen patients underwent endovascular treatment: eight ruptured aneurysms, six aortic dissections, one nonruptured painful aneurysm, and one pseudoaneurysm. No intramural hematoma or penetrating atherosclerotic ulcer was found. The mean age was 64.3 years, and arterial hypertension (100%) and smoking (64.7%) were the major comorbidities. Technical success rate was 93%, and overall 30-day mortality was 6.25%. Conclusion: Endovascular treatment for AAS was feasible. Technical success, 30-day mortality, hospital stay, and procedure time were similar to those of the other series reported in the literature, and the endovascular approach has became the main technique for AAS in our hospital.

Renal Function at Hospital Admission and Mortality Due to Acute Kidney Injury after Myocardial Infarction

Background: The role of an impaired estimated glomerular filtration rate (eGFR) at hospital admission in the outcome of acute kidney injury (AKI) after acute myocardial infarction (AMI) has been underreported. The aim of this study was to assess the influence of an admission eGFR<60 mL/min/1.73 m(2) on the incidence and early and late mortality of AMI-associated AKI. Methods: A prospective study of 828 AMI patients was performed. AKI was defined as a serum creatinine increase of >= 50% from the time of admission (RIFLE criteria) in the first 7 days of hospitalization. Patients were divided into subgroups according to their eGFR upon hospital admission (MDRD formula, mL/min/1.73 m(2)) and the development of AKI: eGFR >= 60 without AKI, eGFR<60 without AKI, eGFR >= 60 with AKI and eGFR<60 with AKI. Results: Overall, 14.6% of the patients in this study developed AKI. The admission eGFR had no impact on the incidence of AKI. However, the admission eGFR was associated with the outcome of AMI-associated AKI. The adjusted hazard ratios (AHR, Cox multivariate analysis) for 30-day mortality were 2.00 (95% CI 1.11-3.61) for eGFR, 60 without AKI, 4.76 (95% CI 2.45-9.26) for eGFR >= 60 with AKI and 6.27 (95% CI 3.20-12.29) for eGFR, 60 with AKI. Only an admission eGFR of <60 with AKI was significantly associated with a 30-day to 1-year mortality hazard (AHR 3.05, 95% CI 1.50-6.19). Conclusions: AKI development was associated with an increased early mortality hazard in AMI patients with either preserved or impaired admission eGFR. Only the association of impaired admission eGFR and AKI was associated with an increased hazard for late mortality among these patients.

Use of Demonstrably Effective Therapies in the Treatment of Acute Coronary Syndromes: Comparison between Different Brazilian Regions. Analysis of the Brazilian Registry on Acute Coronary Syndromes (BRACE)

Background: Little is known in our country about regional differences in the treatment of acute coronary disease. Objective: To analyze the behavior regarding the use of demonstrably effective regional therapies in acute coronary disease. Methods: A total of 71 hospitals were randomly selected, respecting the proportionality of the country in relation to geographic location, among other criteria. In the overall population was regionally analyzed the use of aspirin, clopidogrel, ACE inhibitors / AT1 blocker, beta-blockers and statins, separately and grouped by individual score ranging from 0 (no drug used) to 100 (all drugs used). In myocardial infarction with ST elevation (STEMI) regional differences were analyzed regarding the use of therapeutic recanalization (fibrinolytics and primary angioplasty). Results: In the overall population, within the first 24 hours of hospitalization, the mean score in the North-Northeast (70.5 +/- 22.1) was lower (p < 0.05) than in the Southeast (77.7 +/- 29.5), Midwest (82 +/- 22.1) and South (82.4 +/- 21) regions. At hospital discharge, the score of the North-Northeast region (61.4 +/- 32.9) was lower (p < 0.05) than in the Southeast (69.2 +/- 31.6), Midwest (65.3 +/- 33.6) and South (73.7 +/- 28.1) regions; additionally, the score of the Midwest was lower (p < 0.05) than the South region. In STEMI, the use of recanalization therapies was highest in the Southeast (75.4%, p = 0.001 compared to the rest of the country), and lowest in the North-Northeast (52.5%, p < 0.001 compared to the rest of the country). Conclusion: The use of demonstrably effective therapies in the treatment of acute coronary disease is much to be desired in the country, with important regional differences.

Coronary plaque rupture in patients with myocardial infarction after noncardiac surgery: Frequent and dangerous

Purpose: The pathophysiology of acute coronary syndromes (ACS) after noncardiac surgery is not established yet. Thrombosis over a vulnerable plaque or decreased oxygen supply secondary to anemia or hypotension may be involved. The purpose of this study was to investigate the pathophysiology of ACS complicating noncardiac surgery. Methods: Clinical and angiographic data were prospectively recorded into a database for 120 consecutive patients that had an ACS after noncardiac surgery (PACS), for 120 patients with spontaneous ACS (SACS), and 240 patients with stable coronary artery disease (CAD). Coronary lesions with obstructions greater than 50% were classified based on two criteria: Ambrose's classification and complex morphology. The presence of Ambrose's type II or complex lesions were compared between the three groups. Results: We analyzed 1470 lesions in 480 patients. In PACS group, 45% of patients had Ambrose's type II lesions vs. 56.7% in SACS group and 16.4% in stable CAD group (P < 0.001). Both PACS and SACS patients had more complex lesions than patients in stable CAD group (56.7% vs. 79.2% vs. 31.8%, respectively; P < 0.001). Overall, the independent predictors of plaque rupture were being in the group PACS (P < 0.001, OR 2.86; CI, 1.82-4.52 for complex lesions and P < 0.001, OR 3.43; CI, 2.1-5.6 for Ambrose's type II lesions) or SACS (P < 0.001, OR 8.71; CI, 5.15-14.73 for complex lesions and P < 0.001, OR 5.99; CI, 3.66-9.81 for Ambrose's type II lesions). Conclusions: Nearly 50% of patients with perioperative ACS have evidence of coronary plaque rupture, characterizing a type 1 myocardial infarction. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

Utilização de terapêuticas comprovadamente úteis no tratamento da coronariopatia aguda: comparação entre diferentes regiões brasileiras. Análise do Registro Brasileiro de Síndromes Coronarianas Agudas (BRACE - Brazilian Registry on Acute Coronary Syndromes)

FUNDAMENTO: Pouco se sabe, em nosso meio, sobre diferenças regionais no tratamento da coronariopatia aguda. OBJETIVO: Analisar o comportamento regional relativamente à utilização de terapêuticas comprovadamente úteis na coronariopatia aguda. MÉTODOS: Foram selecionados aleatoriamente 71 hospitais, respeitando-se a proporcionalidade do país em relação à localização geográfica, entre outros critérios. Na população global, foi analisada regionalmente a utilização de AAS, clopidogrel, inibidor da ECA/bloqueador de AT1, betabloqueador e estatina, isoladamente e agrupados por escore individual que variou de 0 (nenhum medicamento utilizado) a 100 (todos utilizados). No infarto com supradesnivelamento de ST (IAMCSST) foram analisadas diferenças regionais sobre utilização de terapêuticas de recanalização (fibrinolíticos e angioplastia primária). RESULTADOS: No global da população, nas primeiras 24 horas de hospitalização, a média de escore na região Norte-Nordeste (70,5 ± 22,1) foi menor (p < 0,05) do que nas regiões Sudeste (77,7 ± 29,5), Centro-Oeste (82 ± 22,1) e Sul (82,4 ± 21). Por ocasião da alta, o escore da região Norte-Nordeste (61,4 ± 32,9) foi menor (p < 0,05) do que nas regiões Sudeste (69,2 ± 31,6), Centro-Oeste (65,3 ± 33,6), e Sul (73,7 ± 28,1); adicionalmente, o escore do Centro-Oeste foi menor (p < 0,05) do que o do Sul. No IAMCSST, o uso de terapêuticas de recanalização foi maior no Sudeste (75,4%, p = 0,001 em relação ao restante do país), e menor no Norte-Nordeste (52,5%, p < 0,001 em relação ao restante do país). CONCLUSÃO: O uso de terapêuticas comprovadamente úteis no tratamento da coronariopatia aguda está aquém do desejável no país, com importantes diferenças regionais.

Association of Proton Pump Inhibitor Use on Cardiovascular Outcomes With Clopidogrel and Ticagrelor Insights From the Platelet Inhibition and Patient Outcomes Trial

Background-The clinical significance of the interaction between clopidogrel and proton pump inhibitors (PPIs) remains unclear. Methods and Results-We examined the relationship between PPI use and 1-year cardiovascular events (cardiovascular death, myocardial infarction, or stroke) in patients with acute coronary syndrome randomized to clopidogrel or ticagrelor in a prespecified, nonrandomized subgroup analysis of the Platelet Inhibition and Patient Outcomes (PLATO) trial. The primary end point rates were higher for individuals on a PPI (n = 6539) compared with those not on a PPI (n = 12 060) at randomization in both the clopidogrel (13.0% versus 10.9%; adjusted hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.04 -1.38) and ticagrelor (11.0% versus 9.2%; HR, 1.24; 95% CI, 1.07-1.45) groups. Patients on non-PPI gastrointestinal drugs had similar primary end point rates compared with those on a PPI (PPI versus non-PPI gastrointestinal treatment: clopidogrel, HR, 0.98; 95% CI, 0.79-1.23; ticagrelor, HR, 0.89; 95% CI, 0.73-1.10). In contrast, patients on no gastric therapy had a significantly lower primary end point rate (PPI versus no gastrointestinal treatment: clopidogrel, HR, 1.29; 95% CI, 1.12-1.49; ticagrelor, HR, 1.30; 95% CI, 1.14-1.49). Conclusions-The use of a PPI was independently associated with a higher rate of cardiovascular events in patients with acute coronary syndrome receiving clopidogrel. However, a similar association was observed between cardiovascular events and PPI use during ticagrelor treatment and with other non-PPI gastrointestinal treatment. Therefore, in the PLATO trial, the association between PPI use and adverse events may be due to confounding, with PPI use more of a marker for, than a cause of, higher rates of cardiovascular events.

Performance of rest myocardial perfusion imaging in the management of acute chest pain in the emergency room in developing nations (PREMIER trial)

Background. Rest myocardial perfusion imaging (MPI) is effective in managing patients with acute chest pain in developed countries. We aimed to define the role and feasibility of rest MPI in low-to-middle income countries. Methods and Results. Low-to-intermediate risk patients (n = 356) presenting with chest pain to ten centers in eight developing countries were injected with a Tc-99m-based tracer, and standard imaging was performed. The primary outcome was a composite of death, non-fatal myocardial infarction (MI), recurrent angina, and coronary revascularization at 30 days. Sixty-nine patients had a positive MPI (19.4%), and 52 patients (14.6%) had a primary outcome event. An abnormal rest-MPI result was the only variable which independently predicted the primary outcome [adjusted odds ratio (OR) 8.19, 95% confidence interval 4.10-16.40, P = .0001]. The association of MPI result and the primary outcome was stronger (adjusted OR 17.35) when only the patients injected during pain were considered. Rest-MPI had a negative predictive value of 92.7% for the primary outcome, improving to 99.3% for the hard event composite of death or MI. Conclusions. Our study demonstrates that rest-MPI is a reliable test for ruling out MI when applied to patients in developing countries. (J Nucl Cardiol 2012;19:1146-53.)

US Food and Drug Administration approval of generic versions of complex biologics: implications for the practicing physician using low molecular weight heparins

Low-molecular-weight heparins (LMWHs) have shown equivalent or superior efficacy and safety to unfractionated heparin as antithrombotic therapy for patients with acute coronary syndromes. Each approved LMWH is a pleotropic biological agent with a unique chemical, biochemical, biophysical and biological profile and displays different pharmacodynamic and pharmacokinetic profiles. As a result, LMWHs are neither equipotent in preclinical assays nor equivalent in terms of their clinical efficacy and safety. Previously, the US Food and Drug Administration (FDA) cautioned against using various LMWHs interchangeably, however recently, the FDA approved generic versions of LMWH that have not been tested in large clinical trials. This paper highlights the bio-chemical and pharmacological differences between the LMWH preparations that may result in different clinical outcomes, and also reviews the implications and challenges physicians face when generic versions of the original/innovator agents are approved for clinical use.