Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved

Metabolic profile of patients with coronary artery disease and comorbid obesity.

Cardiovascular diseases (CVD) are the leading cause of death worldwide. Most CVD can be prevented by  modification of such risk factors as tobacco use, obesity and unhealthy diet, physical inactivity and harmful use of alcohol. Patients with CVD or who are at high cardiovascular risk due to the presence of  risk factors such as dyslipidemia, hypertension, diabetes mellitus type 2,  need early detection and management of these states. The article describes differences between metabolic profile of patients with obesity and coronary artery disease. The study included 58 patients. They were divided into 3 groups: 1st - patients with BMI <30 and CAD, 2nd - patients with BMI>30 and CAD, and 3rd - patients with BMI>30. 1st and 2nd group of patients were treated with atorvastatin in the dose of 40 mg for 2 years, 3rd - untreated. The results indicate that significant difference was faund in the lipid profile between groups of patients treated with atorvastatin in the dose of 40 mg . Transaminases and uric acid levels were different but within the reference range. The difference was found in serum glucose, insulin and HOMA-IR between participants of the 2-nd and other groups. We observed significant insulin resistance in the group of patients with coronary heart disease, obesity, treated with atorvastatin. So, administration of atorvastatin to the patients with IHD and obesity may negatively impact carbohydrate exchange and serve as a possible cause of diabetes melitus type 2 development

Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation : Data From ROCKET AF

M. Kaste on työryhmän ROCKET AF Steering Comm jäsen.Background-Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions. Methods and Results-In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all-cause mortality in the 14 171 participants in the intention-to-treat population. The median age was 73 years, and the mean CHADS(2) score was 3.5. Over 1.9 years of median follow-up, 1214 (8.6%) patients died. Kaplan-Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all-cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33-1.70, P= 75 years (hazard ratio 1.69, 95% CI 1.51-1.90, P Conclusions-In a large population of patients anticoagulated for nonvalvular atrial fibrillation, approximate to 7 in 10 deaths were cardiovascular, whereasPeer reviewe

Modern Advances and Evidence Аccording to the Results of the European Congress of Cardiologists in Amsterdam (30.08–04.09.2013)

Introduction. According to the President of the European Congress of Cardiologists (European Society of Cardiology, ESC) Professor Panos Vardasa, despite the progress of medicine, the diseases of cardiovascular system is now the number one killer of the population of Europe. Clinical trials based on the clinical practice and guidelines were presented at the annual European Congress of Cardiologists in Amsterdam. Aim. To conduct a description and discussion of current successes and evidence of the results of the European Congress of Cardiologists in Amsterdam (30.08-04.09.2013). Materials and methods. Information is provided on the results of the European Congress of Cardiologists in Amsterdam (30.08 – 04.09.2013). The description of clinical trials and updated recommendations on the diagnosis, treatment and prevention of the diseases of the cardiovascular system, including arterial hypertension and cardiovascular disease in patients with diabetes mellitus and pre-diabetes. Results. Among a number of important issues presented during the Congress there were published the results of such studies: HOKUSAI-VTE – using of anticoagulant edoxaban per os for the treatment of venous thromboembolism showed the equal efficacy but better tolerability and safety as compared with warfarin for the primary purpose of low molecular heparin; TASTE – aspiration of blood clots and clots that cause heart attack before opening the artery balloon does not improve the survival compared to using only a balloon dilation or stenting without aspiration; ECHOCRT – the results confirmed the underlying principles that cardiac resynchronization treatment should not be performed for the patients with a narrow QRS complex; DECAAF – the results showed that in patients with atrial fibrillation magnetic resonance imaging prior to ablation allows to determine the extent of damage of the heart tissue. PRAMI – the primary endpoint was the combined death from the cardiac causes, nonfatal myocardial infarction or refractory angina in patients with STEMI and concomitant hemodynamically significant stenosis of the coronary arteries. In addition stenting of the infarct-dependent coronary arteries in all patients with acute elevation of ST-segment, additional preventive coronary artery stenting in the experimental group with hemodynamically significant stenosis showed the significant preference (p <0.001) of such treatment. The Congress also published the first findings on the elimination of the negative impact of lifestyle in the secondary prevention of cardiovascular diseases. At the Congress in Amsterdam there were also presented new recommendations – Recommendations of the European Society of Cardiologists and the European Society of Hypertension on the diagnosis, treatment and prevention of arterial hypertension and Recommendations for the prevention, diagnosis and treatment of cardiovascular disease in patients with diabetes and pre-diabetes. Conclusions. Presented description of the clinical trials and new guidelines for the diagnosis based on their findings, treatment and prevention of the cardiovascular diseases, especially arterial hypertension and cardiovascular diseases in patients with diabetes mellitus and pre-diabetes were provided that must be taken into account in the usual practice of a doctor

Metabolic profile of patients with coronary artery disease and comorbid obesity.

Cardiovascular diseases (CVD) are the leading cause of death worldwide. Most CVD can be prevented by  modification of such risk factors as tobacco use, obesity and unhealthy diet, physical inactivity and harmful use of alcohol. Patients with CVD or who are at high cardiovascular risk due to the presence of  risk factors such as dyslipidemia, hypertension, diabetes mellitus type 2,  need early detection and management of these states. The article describes differences between metabolic profile of patients with obesity and coronary artery disease. The study included 58 patients. They were divided into 3 groups: 1st - patients with BMI 30 and CAD, and 3rd - patients with BMI>30. 1st and 2nd group of patients were treated with atorvastatin in the dose of 40 mg for 2 years, 3rd - untreated. The results indicate that significant difference was faund in the lipid profile between groups of patients treated with atorvastatin in the dose of 40 mg . Transaminases and uric acid levels were different but within the reference range. The difference was found in serum glucose, insulin and HOMA-IR between participants of the 2-nd and other groups. We observed significant insulin resistance in the group of patients with coronary heart disease, obesity, treated with atorvastatin. So, administration of atorvastatin to the patients with IHD and obesity may negatively impact carbohydrate exchange and serve as a possible cause of diabetes melitus type 2 development

Досвід антикоагулянтної терапії у пацієнтів з тромбоемболією легеневих артерій

Objective — to perform the comparative analysis of the administration of two anticoagulants (dabigatran and warfarin) for the treatment of pulmonary embolism. The demographic and clinical features of the patients in both groups were studied, the clinical likelihood of this pathology according to the original version of the Geneva scale was evaluated, the risks were stratified depending on the symptoms of the clinical course and the frequency of the individual factors’ prevalence. Moreover, the estimations have been given to the bleeding risk, and the frequency of undesirable side effects and new serious cardiovascular complications depending on the selected anticoagulant have been revealed. The complex preventive approach has been proposed with the use of diagnostic scales HAS­BLED an ATRIA Bleeding Risk Score with the aim of reduction of bleeding risk against the background of anticoagulant therapy in patients with pulmonary embolism.Цель работы — сравнительный анализ применения двух антикоагулянтов — дабигатрана и варфарина с целью лечения тромбоэмболии легочных артерий (ТЭЛА). Исследованы демографические и клинические особенности пациентов обеих групп, оценена клиническая вероятность данной патологии согласно оригинальной версии Женевской шкалы, стратифицированы риски в зависимости от симптомов клинического течения и частоты распространенности отдельных факторов. Также спрогнозированы риски кровотечений, выявлена частота нежелательных побочных эффектов и новых серьезных сердечно-сосудистых нарушений в зависимости от выбранного антикоагулянта. Предложен комплексный профилактический подход с использованием диагностических шкал HAS-BLED и ATRIA Bleeding Risk Score с целью снижения риска кровотечений на фоне антикоагулянтной терапии у пациентов с ТЭЛА.Мета роботи — порівняльний аналіз застосування двох антикоагулянтів — дабігатрану і варфарину з метою лікування тромбоемболії легеневої артерії (ТЕЛА). Досліджено демографічні та клінічні особливості пацієнтів двох груп, оцінено клінічну вірогідність даної патології згідно оригінальної версії Женевської шкали, стратифіковано ризики залежно від симптомів клінічного перебігу та частоти поширеності окремих факторів. Також спрогнозовано оцінку ризику кровотеч, виявлено частоту небажаних побічних ефектів та нових серйозних серцево-судинних ускладнень залежно від обраного антикоагулянту. Запропоновано комплексний профілактичний підхід з використанням діагностичних шкал HAS-BLED та ATRIA Bleeding Risk Score з метою зниження ризику кровотеч на фоні антикоагулянтної терапії у пацієнтів з ТЕЛА

Metabolic profile of patients with coronary artery disease and comorbid obesity

Cardiovascular diseases (CVD) are the leading cause of death worldwide. Most CVD can be prevented by modification of such risk factors as tobacco use, obesity and unhealthy diet, physical inactivity and harmful use of alcohol. Patients with CVD or who are at high cardiovascular risk due to the presence of risk factors such as dyslipidemia, hypertension, diabetes mellitus type 2, need early detection and management of these states. The article describes differences between metabolic profile of patients with obesity and coronary artery disease. The study included 58 patients. They were divided into 3 groups: 1st - patients with BMI 30 and CAD, and 3rd - patients with BMI>30. 1st and 2nd group of patients were treated with atorvastatin in the dose of 40 mg for 2 years, 3rd - untreated. The results indicate that significant difference was faund in the lipid profile between groups of patients treated with atorvastatin in the dose of 40 mg . Transaminases and uric acid levels were different but within the reference range. The difference was found in serum glucose, insulin and HOMA-IR between participants of the 2-nd and other groups. We observed significant insulin resistance in the group of patients with coronary heart disease, obesity, treated with atorvastatin. So, administration of atorvastatin to the patients with IHD and obesity may negatively impact carbohydrate exchange and serve as a possible cause of diabetes melitus type 2 development

Cause of death and predictors of all-cause mortality in anticoagulated patients with nonvalvular atrial fibrillation: Data from ROCKET AF

Background-Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions. Methods and Results-In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all-cause mortality in the 14 171 participants in the intentionto- treat population. The median age was 73 years, and the mean CHADS2 score was 3.5. Over 1.9 years of median follow-up, 1214 (8.6%) patients died. Kaplan-Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all-cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33-1.70, P&lt;0.0001) and age 6575 years (hazard ratio 1.69, 95% CI 1.51-1.90, P&lt;0.0001) were associated with higher all-cause mortality. Multiple additional characteristics were independently associated with higher mortality, with decreasing creatinine clearance, chronic obstructive pulmonary disease, male sex, peripheral vascular disease, and diabetes being among the most strongly associated (model C-index 0.677). Conclusions-In a large population of patients anticoagulated for nonvalvular atrial fibrillation, 487 in 10 deaths were cardiovascular, whereas &lt;1 in 10 deaths were caused by nonhemorrhagic stroke or systemic embolism. Optimal prevention and treatment of heart failure, renal impairment, chronic obstructive pulmonary disease, and diabetes may improve survival

Ezetimibe added to statin therapy after acute coronary syndromes

BACKGROUND: Statin therapy reduces low-density lipoprotein (LDL) cholesterol levels and the risk of cardiovascular events, but whether the addition of ezetimibe, a nonstatin drug that reduces intestinal cholesterol absorption, can reduce the rate of cardiovascular events further is not known. METHODS: We conducted a double-blind, randomized trial involving 18,144 patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and had LDL cholesterol levels of 50 to 100 mg per deciliter (1.3 to 2.6 mmol per liter) if they were receiving lipid-lowering therapy or 50 to 125 mg per deciliter (1.3 to 3.2 mmol per liter) if they were not receiving lipid-lowering therapy. The combination of simvastatin (40 mg) and ezetimibe (10 mg) (simvastatin-ezetimibe) was compared with simvastatin (40 mg) and placebo (simvastatin monotherapy). The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, unstable angina requiring rehospitalization, coronary revascularization ( 6530 days after randomization), or nonfatal stroke. The median follow-up was 6 years. RESULTS: The median time-weighted average LDL cholesterol level during the study was 53.7 mg per deciliter (1.4 mmol per liter) in the simvastatin-ezetimibe group, as compared with 69.5 mg per deciliter (1.8 mmol per liter) in the simvastatin-monotherapy group (P<0.001). The Kaplan-Meier event rate for the primary end point at 7 years was 32.7% in the simvastatin-ezetimibe group, as compared with 34.7% in the simvastatin-monotherapy group (absolute risk difference, 2.0 percentage points; hazard ratio, 0.936; 95% confidence interval, 0.89 to 0.99; P = 0.016). Rates of pre-specified muscle, gallbladder, and hepatic adverse effects and cancer were similar in the two groups. CONCLUSIONS: When added to statin therapy, ezetimibe resulted in incremental lowering of LDL cholesterol levels and improved cardiovascular outcomes. Moreover, lowering LDL cholesterol to levels below previous targets provided additional benefit