Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients

Background Patients with acute medical illnesses are at prolonged risk for venous thrombosis. However, the appropriate duration of thromboprophylaxis remains unknown. Methods Patients who were hospitalized for acute medical illnesses were randomly assigned to receive subcutaneous enoxaparin (at a dose of 40 mg once daily) for 10±4 days plus oral betrixaban placebo for 35 to 42 days or subcutaneous enoxaparin placebo for 10±4 days plus oral betrixaban (at a dose of 80 mg once daily) for 35 to 42 days. We performed sequential analyses in three prespecified, progressively inclusive cohorts: patients with an elevated d-dimer level (cohort 1), patients with an elevated d-dimer level or an age of at least 75 years (cohort 2), and all the enrolled patients (overall population cohort). The statistical analysis plan specified that if the between-group difference in any analysis in this sequence was not significant, the other analyses would be considered exploratory. The primary efficacy outcome was a composite of asymptomatic proximal deep-vein thrombosis and symptomatic venous thromboembolism. The principal safety outcome was major bleeding. Results A total of 7513 patients underwent randomization. In cohort 1, the primary efficacy outcome occurred in 6.9% of patients receiving betrixaban and 8.5% receiving enoxaparin (relative risk in the betrixaban group, 0.81; 95% confidence interval [CI], 0.65 to 1.00; P=0.054). The rates were 5.6% and 7.1%, respectively (relative risk, 0.80; 95% CI, 0.66 to 0.98; P=0.03) in cohort 2 and 5.3% and 7.0% (relative risk, 0.76; 95% CI, 0.63 to 0.92; P=0.006) in the overall population. (The last two analyses were considered to be exploratory owing to the result in cohort 1.) In the overall population, major bleeding occurred in 0.7% of the betrixaban group and 0.6% of the enoxaparin group (relative risk, 1.19; 95% CI, 0.67 to 2.12; P=0.55). Conclusions Among acutely ill medical patients with an elevated d-dimer level, there was no significant difference between extended-duration betrixaban and a standard regimen of enoxaparin in the prespecified primary efficacy outcome. However, prespecified exploratory analyses provided evidence suggesting a benefit for betrixaban in the two larger cohorts. (Funded by Portola Pharmaceuticals; APEX ClinicalTrials.gov number, NCT01583218. opens in new tab.

Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia

BACKGROUND Patients with elevated triglyceride levels are at increased risk for ischemic events. Icosapent ethyl, a highly purified eicosapentaenoic acid ethyl ester, lowers triglyceride levels, but data are needed to determine its effects on ischemic events. METHODS We performed a multicenter, randomized, double-blind, placebo-controlled trial involving patients with established cardiovascular disease or with diabetes and other risk factors, who had been receiving statin therapy and who had a fasting triglyceride level of 135 to 499 mg per deciliter (1.52 to 5.63 mmol per liter) and a low-density lipoprotein cholesterol level of 41 to 100 mg per deciliter (1.06 to 2.59 mmol per liter). The patients were randomly assigned to receive 2 g of icosapent ethyl twice daily (total daily dose, 4 g) or placebo. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina. The key secondary end point was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. RESULTS A total of 8179 patients were enrolled (70.7% for secondary prevention of cardiovascular events) and were followed for a median of 4.9 years. A primary end-point event occurred in 17.2% of the patients in the icosapent ethyl group, as compared with 22.0% of the patients in the placebo group (hazard ratio, 0.75; 95% confidence interval [CI], 0.68 to 0.83; P<0.001); the corresponding rates of the key secondary end point were 11.2% and 14.8% (hazard ratio, 0.74; 95% CI, 0.65 to 0.83; P<0.001). The rates of additional ischemic end points, as assessed according to a prespecified hierarchical schema, were significantly lower in the icosapent ethyl group than in the placebo group, including the rate of cardiovascular death (4.3% vs. 5.2%; hazard ratio, 0.80; 95% CI, 0.66 to 0.98; P=0.03). A larger percentage of patients in the icosapent ethyl group than in the placebo group were hospitalized for atrial fibrillation or flutter (3.1% vs. 2.1%, P=0.004). Serious bleeding events occurred in 2.7% of the patients in the icosapent ethyl group and in 2.1% in the placebo group (P=0.06). CONCLUSIONS Among patients with elevated triglyceride levels despite the use of statins, the risk of ischemic events, including cardiovascular death, was significantly lower among those who received 2 g of icosapent ethyl twice daily than among those who received placebo. (Funded by Amarin Pharma; REDUCE-IT ClinicalTrials.gov number, NCT01492361

Безбольова ішемія міокарда при цукровому діабеті 2 типу

Increased interest to the high prevalence of the phenomenon of silent myocardial ischemia was detected nowadays in the literature. Aim. To study role of the diabetes mellitus in the development of the silent myocardial ischemia. To underline main patophysiological features, diagnostic approaches and main streams in the treatment. Methods and results. Literature review of the Ukrainian and foreign issues.Results. Special place among the risk factors for CHD is type 2 diabetes takes silent myocardial ischemia. The prevalence of silent myocardial ischemia in patients with diabetes is significantly higher (2-7 times) than in those without diabetes. Many attribute this to the higher incidence of atherosclerosis and coronary heart disease in the general population in diabetic patients, but attention is drawn to a complication of diabetes - diabetic autonomic neuropathy, particularly cardiovascular its shape. Analysis of the literature showed that, despite the obvious successes in the study of  SMI, still remain differences in views on the possible causes and mechanisms of this phenomenon CHD.Conclusion. The literature review provides information about the pathophysiological features of SMI in diabetes mellitus type 2, presented data on its prevalence, methods of diagnosis and treatment of the main directions reflected the prognostic significance of silent myocardial ischemia in patients with type 2 diabetes.В последние десятилетия к проблеме безболевой ишемии миокарда наблюдается повышенный интерес, что обусловлено большой распространённостью этого феномена и указаниями на неблагоприятное прогностическое значение ББИМ у больных без клинических проявлений ИБС, но имеющих факторы риска этого заболевания. Особое место среди факторов риска ИБС занимает сахарный диабет 2 типа. Распространённость безболевой ишемии миокарда среди больных с сахарным диабетом значительно выше (в 2–7 раз), чем у лиц без диабета. Многие связывают это с более высокой распространённостью атеросклероза и ИБС в целом в популяции диабетических пациентов. Но обращает на себя внимание осложнение сахарного диабета – диабетическая автономная нейропатия, в частности кардиоваскулярная её форма. Анализ литературы показывает, что, несмотря на очевидные успехи в изучении ББИМ, до настоящего времени остаются разногласия во взглядах на возможные причины и механизмы формирования этого феномена ИБС. В обзоре литературы представлены сведения о патофизиологических особенностях ББИМ при сахарном диабете 2 типа, изложены данные о её распространённости, методах диагностики и основных направлениях в лечении, отражено прогностическое значение безболевой ишемии миокарда у лиц с сахарным диабетом 2 типа.В останні десятиріччя до проблеми безбольової ішемії міокарда спостерігається підвищений інтерес, що зумовлено великою поширеністю цього феномена та вказівками на несприятливе прогностичне значення ББІМ у хворих без клінічних проявів ІХС, але які мають фактори ризику цього захворювання. Особливе місце серед факторів ризику ІХС посідає цукровий діабет 2 типу. Поширеність безбольової ішемії серед хворих із цукровим діабетом є значно вищою (у 2–7 разів), ніж в осіб без діабету. Багато хто пов’язує це з більш високою поширеністю атеросклерозу та ІХС в цілому серед діабетичних пацієнтів, однак привертає увагу ускладнення цукрового діабету – діабетична автономна нейропатія, зокрема кардіоваскулярна її форма. Аналіз літератури показує, що, незважаючи на очевидні успіхи у вивченні ББІМ, дотепер залишаються розбіжності в поглядах на можливі причини та механізми формування цього феномена ІХС. В огляді літератури представлені відомості про патофізіологічні особливості ББІМ при цукровому діабеті 2 типу, викладені дані про її поширеність, методи діагностики та основні напрями в лікуванні, показано прогностичне значення безбольової ішемії міокарда в осіб з цукровим діабетом 2 типу

Silent myocardial ischemia in patients with diabetes mellitus type 2

Increased interest to the high prevalence of the phenomenon of silent myocardial ischemia was detected nowadays in the literature. Aim. To study role of the diabetes mellitus in the development of the silent myocardial ischemia. To underline main patophysiological features, diagnostic approaches and main streams in the treatment. Methods and results. Literature review of the Ukrainian and foreign issues.Results. Special place among the risk factors for CHD is type 2 diabetes takes silent myocardial ischemia. The prevalence of silent myocardial ischemia in patients with diabetes is significantly higher (2-7 times) than in those without diabetes. Many attribute this to the higher incidence of atherosclerosis and coronary heart disease in the general population in diabetic patients, but attention is drawn to a complication of diabetes - diabetic autonomic neuropathy, particularly cardiovascular its shape. Analysis of the literature showed that, despite the obvious successes in the study of SMI, still remain differences in views on the possible causes and mechanisms of this phenomenon CHD. Conclusion. The literature review provides information about the pathophysiological features of SMI in diabetes mellitus type 2, presented data on its prevalence, methods of diagnosis and treatment of the main directions reflected the prognostic significance of silent myocardial ischemia in patients with type 2 diabetes

Зміни варіабельності ритму серця у хворих на артеріальну гіпертензію у процесі амбулаторного лікування

Actuality of the heart rate variability study in patients with hypertension is underlined with high risk of hypertension complications development and the influence of the autonomic nervous system that changes the tone, affects not only the course of the disease but also increases the risk of death.The aim was to study heart rate variability with conventional methods, in order to increase the efficiency of the hypertension treatment with telmisartan and bisoprolol in 35 patients suffering from high blood pressure with degree I and II in an ambulatory care clinic.Results. It has been proven that the treatment with bisoprolol and telmisartan in patients with hypertension degree I and II is accompanied by a significant reduction of the sympathetic division activity of the autonomic nervous system, indicating positive change of the autonomic imbalance and increased activity of the parasympathetic system, therefore accompanied by significant reduction in the low frequency spectrum of the sympathetic nervous system in relation with the cardiac activity and the confirmed indicators LF / HF.Актуальность исследования вариабельности сердечного ритма у больных АГ обусловлена высоким риском развития осложнений АГ и особенностями влияния вегетативной нервной системы, поскольку изменения её тонуса не только неблагоприятно влияют на течение заболевания, но и повышают риск летальных исходов.С целью повышения эффективности лечения АГ телмисартаном и бисопрололом у 35 пациентов с артериальной гипертензией I и II степени в амбулаторних условиях было проведено исследование вариабельности сердечного ритма общепринятыми методами.Установлено, что у больных АГ I и II степени лечение бисопрололом и тел-мисартаном сопровождалось существенным снижением активности симпатического отдела вегетативной нервной системы, что свидетельствовало о положительной коррекции вегетативного дисбаланса и повышении активности парасимпатического её отдела и, как следствие, сопровождалось существенным снижением мощности спектра низких частот симпатического отдела вегетативной нервной системы в отношении сердечной деятельности и подтверждалось показателем LF/HF, что также свидетельствовало о снижении тонуса симпатического звена вегетативной нервной системы на деятельность сердца и уровень АД.Актуальність дослідження варіабельності серцевого ритму у хворих на АГ є зумовленою високим ризиком розвитку ускладнень АГ та особливостями впливу вегетативної нервової системи, оскільки зміни її тонусу не тільки несприятливо впливають на перебіг захворювання, але й підвищують ризик летальних наслідків.З метою підвищення ефективності лікування телмісартаном і бісопрололом хворих на АГ у 35 хворих на артеріальну гіпертензію І та ІІ ступенів в амбулаторних умовах дослідили варіабельність серцевого ритму загальноприйнятими методами.Встановили, що у хворих на АГ І та ІІ ступенів лікування бісопрололом і телмісартаном супроводжувалось істотним зниженням активності симпатичного відділу вегетативної нервової системи, що свідчило про позитивну корекцію вегетативного дисбалансу та підвищення активності парасимпатичного її відділу і, як наслідок, супроводжувалось істотним зниженням потужності спектра низьких частот симпатичного відділу вегетативної нервової системи стосовно серцевої діяльності та підтверджувалось показником LF/HF, що також свідчило про зниження впливу симпатичної ланки вегетативної нервової системи на діяльність серця та рівень АТ

Changes in heart rate variability in patients with hypertension under outpatient stage treatment

Actuality of the heart rate variability study in patients with hypertension is underlined with high risk of hypertension complications development and the influence of the autonomic nervous system that changes the tone, affects not only the course of the disease but also increases the risk of death. The aim was to study heart rate variability with conventional methods, in order to increase the efficiency of the hypertension treatment with telmisartan and bisoprolol in 35 patients suffering from high blood pressure with degree I and II in an ambulatory care clinic. Results. It has been proven that the treatment with bisoprolol and telmisartan in patients with hypertension degree I and II is accompanied by a significant reduction of the sympathetic division activity of the autonomic nervous system, indicating positive change of the autonomic imbalance and increased activity of the parasympathetic system, therefore accompanied by significant reduction in the low frequency spectrum of the sympathetic nervous system in relation with the cardiac activity and the confirmed indicators LF / HF

Cohort Prospective Study of the Heart and Vessel Condition in Patients with Ischemic Heart Disease Combined with Type 2 Diabetes

The article is devoted to the evaluation of peculiarities of cardiac hemodynamics in patients with type 2 diabetes mellitus (type 2 diabetes) in combination with ischemic heart disease (IHD). The main parameters of the function of the heart and structural and functional changes of the common carotid artery (SCA), features of carbohydrate and lipid metabolism have been studied.Aim: To evaluate the peculiarities of cardiac hemomodynamics in patients with type 2 diabetes in combination with IHD and to find correlations with other cardiovascular risk factors in these patients.Materials and methods: 100 patients with IHD were included in the study: patients with type 2 diabetes in combination with coronary heart disease, stable angina pectoris (n=60) – 1 group, 2 groups – patients with coronary heart disease: stable angina pectoris II-III FC without violations of carbohydrate metabolism (n = 40). In the study of patients, the analysis of complaints, cardiological anamnesis, vascular risk factors, objective research, clinical and laboratory and clinical and instrumental research methods were performed, which included ECG, Holter monitoring of ECG, Echo-CG, and vegetative ECG tests.Results: On the basis of the conducted studies we revealed more severe violations of the diastolic function of the left ventricle, increased volumetric parameters of the heart, thickening of the intima-media complex in patients with coronary heart disease on the background of type 2 diabetes. According to the results of vegetative tests, 71.7% of patients in group 1 revealed signs of diabetic autonomic cardiac neuropathy (DANS). Episodes of painless myocardial ischemia (BBIM) in patients in group 1 were twice as likely to occur in group 2 patients (45% of the total number of patients with diabetes mellitus) than in patients without type 2 diabetes (20% of the total number of patients without diabetes type 2).Conclusions: Significant violations of lipid metabolism, significant violations of autonomic innervation, including the sympathetic nervous system, and longer duration of type 2 diabetes (13.2±6.23) years were characteristic for patients with DANS, in combination with BBIM. In patients with type 2 diabetes with DANS signs, an increase in the diameter of the CCA and the thickness of the intima-media complex was observed, indicating a more pronounced atherosclerotic vascular trauma in the central nervous system, and is an independent predictor of acute cardiovascular and cerebrovascular events. The presence of type 2 diabetes in patients with coronary heart disease accelerates the progression of LV remodelling and enhances myocardial dysfunction of the lungs, which is also one of the explanations for the higher risk of cardiac events in patients with coronary artery disease of the concomitant type 2 diabetes. It is advisable for all patients with type 2 diabetes to conduct an ultrasound examination of the heart with an estimate of intima-media thickness, as well as daily ECG monitoring for the early detection of atherosclerosis, episodes of BBIM, and timely treatmen

The Efficacy and Safety of Bilastine in the Treatment of Perennial Allergic Rhinitis in Patients with Moderate and Severe Forms of the Disease. Comparison of bilastine 20 mg with desloratadine 5 mg Сергей

Background: Bilastine is a new non-sedating H1 antihistamine approved for the symptomatic treatment of allergic rhinoconjunctivitis (ARC) and urticaria in adults and children over 12 years of age. In this paper, bilastine was compared with desloratadine in the treatment of various forms of allergic rhino-conjunctivitis classified according to the ARIA recommendations.Materials and Methods: This was an international, multi-centre, open-label, prospective randomized, parallel-group, phase III study which enrolled a total of 226 patients with ARC. The diagnosis of the allergic rhino-conjunctivitis was established on the basis of nasal and non-nasal symptoms and confirmed by the skin prick test. Patients were randomized to one of the two treatment groups: bilastine 20 mg daily or desloratadine 5 mg daily.Results: The results for the primary and secondary endpoints showed a comparable reduction in TSS, NSS, and NNSS from the baseline to the end of the treatment between the treatment groups, with slightly better effects for bilastine. Additional tests carried out in the subgroup of patients with moderate / severe persistent (MSP) ARC demonstrated comparable results for the bilastine and desloratadine groups regarding the mean change in TSS from the baseline until the 28th day, except for the sneezing score, for which bilastine showed the higher response (-1.60 ± 0.60 vs. -1.39 ± 0.63), and a statistically significant difference between the treatment groups regarding AUC for TSS ( -26.07 [95% CI: -48.6, -3.53] p = 0.024), NNSS (-10.51 [95% CI:-19.42, -1.59] p = 0.021), the sneezing score (-4.79 [95% CI:-9.06, -0.51] p = 0.028) and the ocular redness score (-5.50 [95% CI: -8.91, -2.08] p = 0.02).Conclusion: In general, bilastine and desloratadine showed a comparable efficacy profile in the treatment of ARC; however, the results obtained in the subgroup of patients with moderate / severe persistent symptoms indicate that bilastine has a stronger therapeutic effec