Results of bicycle exercise stress test in patients with stable coronary heart disease depending on the angiographic signs of atherosclerotic lesions of coronary arteries

The aim. To identify features of exercise response in coronary heart disease (CHD) patients depending on coronary artery condition and to identify factors associated with a positive test in patients with no obstructive coronary artery disease (INOCA). Materials and methods. The study included 105 patients diagnosed with stable coronary artery disease (CAD) who were hospitalized at the City Clinical Hospital No. 8 of the Kharkiv City Council. The criteria for diagnosis of ischemia with no obstructive coronary artery disease (INOCA) were met by 53 patients who formed group I. Group II included 52 patients who were consistently hospitalized in the period from June to December 2020, and had obstructive CAD for more than 50 % according to their coronary angiography (CAG). Results. According to the results of bicycle exercise stress test, a positive test was significantly more often registered in group II – n=30 (57.7 %) patients compared to group I – n=19 (35.8 %) patients (p=0.0249). The duration of the test in patients of group I was significantly longer than 420 seconds [290–540], compared with group II – 300.0 [210.0–540.0] (р=0.0352). Also, in patients in group II, the maximum volume of the test performed was probably lower than in group I (p=0.0324). When calculating the double product, it was also found that in group I its value was significantly higher compared to group II (p=0.0292). In group I there was a significantly higher rate of chronotropic reserve (44.0 [26.0–60.0]), compared with group II (p=0.0168). Elevated total cholesterol (above 5 mmol/l) is a statistically significant and independent factor of a positive exercise test in patients with INOCA (OR, 1.98 [0.9992-3.926], p=0.05). A correlation was found between the level of exercise tolerance and smoking in INOCA-patients (r =-0.388975, p=0.010899). Patients who underwent MINOCA also showed reduced tolerance to exercise (r=-0.3104, p=0.042721) Conclusions. The sensitivity of bicycle exercise stress test in patients with CAD depends on the presence and severity of atherosclerotic lesions of the coronary arteries (63 % in stenotic atherosclerosis, 36 % in no obstructive coronary arteries. It was found that exercise test duration, double product, chronotropic and inotropic reserve of the heart in patients with a positive exercise test with INOCA were significantly higher compared with patients with obstructive CAD. Independent factors associated with a positive exercise test in patients with no obstructive CAD are an increase in total cholesterol (multivariate regression logistic analysis)

CLINICAL IMPLICATIONS OF NT PROBNP LEVEL IN PATIENTS WITH MYOCARDIAL INFARCTION COMPLICATED BY ATRIAL FIBRILLATION

Our aim was to study the predictive value of NT proBNP regarding the risk of AF and clinical features in acute phase of ST-segment elevation MI (STEMI). Methods. We examined 56 patients with STEMI and AF who did undergo the primary PCI. 35 (62.5 %) of patients had the new-onset AF (group 1), 21 (37.5 %) had pre-existing AF (group 2). Control group consisted of 60 patients with STEMI without AF (group 3). Results. Group 3 patients were more likely to be smokers than patients in group 2. They had lower admission heart rate and glycemia, lower NT proBNP, higher hemoglobin and ejection fraction. Patients in group 1 were more likely to have anterior MI, left anterior descending artery as an infarction-related artery (IRA) and adverse cardiac events (MACEs). Patients in group 2 had higher left atrium end-systolic diameter and were more likely to have three-vessel injury. NT proBNP correlated positively with age, admission glycemia, mean PA pressure and negatively – with GFR. ROC analysis had shown the cut-off point of NT proBNP level for prediction of AF was >1050 pg/ml. Cut-off point for prediction of the risk of MACE in STEMI complicated with AF was >2189 pg/ml. Discussion. It was shown that NT proBNP is higher in STEMI patients who have AF. Increased NT proBNP is associated with the risk of adverse events in acute STEMI phase. NT proBNP level can be utilized as AF predictor in STEMI patients and as predictor of MACEs in patients with STEMI and AF

Визначення чинників, які асоційовані з віддаленим прогнозом у хворих з інфарктом міокарда правого шлуночка, за даними метода Каплана-Мейера

Aim of research.  To determine the influence of myocardium infarction (MI) of the right ventricle (RV) on the development of cardio-vascular (CV) events at the long-term observation and to establish the role of factors, associated with the unfavorable prognosis of patients with myocardium infarction of the right ventricle.Materials and methods. There were examined 309 patients with Q-MI of the left ventricle (LV), age 65,5 ± 4,42years old. Patients were divided in 3 groups:  1 group - 155 patients with MI RV on the background of Q-MI of the back wall of the LV, 2 group - 53 patients with MI RV on the background of Q-MI of the circular localization, 3 group - 101 patients with Q-MI of the back wall of LV. The observation period was 30,6 ± 4,5 months. The end points were considered as: unstable angina (UA), repeated MI, acute disorders of the cerebral blood circulation (ADCB), hospitalization because of heart failure (HF) decompensation and CV-death. The statistical researches included the method of Kaplane-Meyer and χ2-Pearson test.Results. After 30,6 months of observation the frequency of CV-complications was reliably higher in both groups of patients with MI RV (р = 0,0039; р = 0,00012) comparing with the third group. There was no any essential difference in the frequency of end points between 1 and 2 group with MI RV (p = 0,053). The planned revascularization is connected with the increase of the life quality of patients after MI RV after the reliable influence of CV-death index. In 30,6 months of rehabilitation men and women in both groups with MI RV had no essential difference in the frequency of repeated MI, ADCB, HF and HF-hospitalizations, but the index of CV-death was reliably higher among female persons (р <0,05).Conclusion. The presence of MI RV in patients with Q-MI LV is connected with the higher frequency of CV-events during 30,6 months of observation. MI RV in women is associated with the essential increase of the risk of CV-mortality during 30,6 months of observation. The delayed revascularization is associated with the decrease of the risk of CV-events development, without influencing CV-death indexДоведено, що наявність інфаркту міокарду правого шлуночка у хворих з Q-інфарктом міокарда лівого шлуночка асоціюється з достовірним збільшенням частоти серцево-судинних ускладнень протягом 30,6 місяців спостереження. Проведення планової реваскуляризації супроводжується покращенням якості життя без впливу на показник смертності. Гендерні особливості перебігу постінфарктного періоду полягають в більш високому показнику смертності серед жіно

Вплив кверцетину на динамику С-реактивного протеїну та віддалений прогноз хворих з інфарктом міокарда правого шлуночка на фоні Q-інфаркту міокарда лівого шлуночка

Aim of research: to estimate the influence of quercetin on the dynamic of C-reactive protein, course of myocardial infarction and long-term prognosis of patients with myocardial infarction of the right ventricle on the background of Q-MI of the left ventricle.Materials and methods. There were examined 208 patients with myocardial infarction of the right ventricle: the 1st group - 155 patients on the background of the Q-MI of the posterior  wall of the left ventricle,  and the 2nd group – 53 patients with right ventricle MI on the  background of Q-MI of the left ventricle of the circular localization, aged 64.11±0.78 years. Quercetin was prescribed from the 1st day of myocardial infarction: in the 1st group – in 88 (55.5%) patients, in the 2nd  group – in 32 (60.4%) patients. The concentration of C-reactive protein in blood serum was determined on the 2nd day of myocardial infarction and in 6 months with enzyme immunoassay analysis using HS-CRP EIA (Vienna, Austria).Follow-up was (30.6±4.5) months. Study endpoints were: cardiovascular death, unstable angina, recurrent myocardial infarction, heath failure hospitalizations  and stroke.Results. The therapy by quercetin was accompanied by the reliable decrease of the risk of fatal arrhythmias, early post-infarction angina, manifestations of the acute and chronic heart failure in the acute period of myocardial infarction of the right ventricle. Quercetin prescription was associated with the reliable decrease of the C-reactive protein (р=0.006) levels in 6 months after myocardial  infarction. There was established the predictor role of C-reactive protein after 6 months after infarction in the development of recurrent myocardial infarction (11.4%), unstable angina (7.7%) during 30.6 months. The therapy by quercetin in the 1st group was associated with the decrease of the frequency of recurrent myocardial infarctions (р=0.012), heart failure hospitalizations (р=0.0056) and cases of the cardio-vascular death (р=0.039); in the 2nd group – with the decrease of cases of unstable angina (р=0.012) and cardio-vascular death (р=0.01) comparing with patients on the standard therapy.Conclusion. Using of the  quercetin in addition to the standard therapy in patients with myocardium infarction of the right ventricle is associated with the reliable decrease of cardiovascular events, particularly cardiovascular death, hospitalizations because of unstable angina and heart failure during 30.6 months of observation and positive dynamics of the C-reactive protein in 6 months after myocardium infarction. The level of C-protein in 6 months after myocardium infarction is an additional risk factor of cardiovascular complications during 30.6 months after myocardium infarction of the right ventricleВикористання кверцетину у хворих з інфарктом міокарду правого шлуночка супроводжується зменшенням кількості фатальних ускладнень гострого періоду, достовірною позитивною динамікою С-реактивного протеїну та зниженням ризику стенокардії та серцевої недостатності через 6 місяців. Встановлено прогностичне значення С-реактивого протеїну, визначеного через 6 місяців після інфаркту міокарду як додаткового фактора несприятливого прогнозу. Доведено, що терапія кверцетином у хворих з інфарктом міокарду правого шлуночка асоціюється з покращенням віддаленого прогнозу протягом 30,6 місяці

Дослідження показників, що впливають на клінічний прогноз та ремоделювання серця у віддаленому періоді у хворих на інфаркт міокарду з елевацією сегменту ST

Aim. To determine factors, connected with the unfavorable prognosis of patients with myocardium infarction (MI) with ST element elevation, who underwent the thrombolytic therapy (TLT).Materials and methods. There were examined 100 patients with MI with ST segment elevation, who underwent TLT, admitted at hospital during the first 6 hours of the disease. The average time of TLT was 154±75,56 minutes, TLT was realized at the pre-hospital stage in 35(38,5 %) patients.Blood samples for determining biochemical parameters, especially asymmetric dimethylarginine (ADMA) and high-sensitive C-reactive protein (CRP), were taken at admission at hospital. ADMA level was determined using the high-effective liquid chromatography, the level of high-sensitive CRP – by the immunoturbdiametric analysis. For determining the allele condition of T786C polymorphism of the gene of endothelial NO synthase (eNOS), there was used polymerase chain reaction. All patients underwent echocardioscopy (EchoCS).  Patients were examined repeatedly in 1 year. The information as to undesirable clinical events was accessible in 91 persons, 60 patients underwent the repeated EchoCS.Results. Undesirable clinical events took part in 13 (14,3 %) of 91 patients. Among patients, who underwent undesirable events, reliably more patients had the previous localization of MI (39,7 % and 76,9 %, respectively, р=0,03). They had also the more heart rate for the second day of the disease (71,01±12,38 st/min and 77,36±7,84 st/min, respectively, p=0,045). The reliably more part of patients from this group had angina before the development of the current MI - 1 (1,3 %) and 3 ( 23,1 %), respectively, р=0,009. Patients, who had undergone undesirable events, had the reliably higher level of the high-sensitive CRP at admission to hospital (37,47±28,08 against 11,70±12,21in І group, р=0,006). The regression analysis established that the increase of the risk of undesirable events by 9,9 % is connected with angina before MI, by 7,3 % with the previous MI localization, by 5,6 % with the decrease of the emission fraction (EF) in the acute period of MI, by 5,1 % with the increase of the level of the high-sensitive CRP, by 5,1 % with the decrease of smoking length, and by 5,1 % with female sex.The left ventricle (LV) remodeling (increment of the end diastolic volume (EDV) over 20 % comparing with the results of the first EchCS) was observed in 13 (21,7 %) of 60 examined persons. It was revealed, that patients with the further development of LV remodeling had better parameters of the intracardiac hemodynamics in the acute period of MI – less values of LV EDV (р=0,028), LV end systolic volume (ESV) (р=0,049), LV myocardium mass (р=0,031). At the analysis of laboratory data, it was revealed, that these patients had the reliably higher level of the high-sensitive CRP and ADMA. The method of regression analysis demonstrated that the increase of the risk of LV remodeling is connected with the less size of the left atrium by 12,5 % and by 9,1 % - with the less MMLV in the acute MI period, by 5,9 % with smoking at the moment of MI, by 5,1 % with the increase of the level of high-sensitive CRP, by 4,7 % with angina before MI, by 4,6 % with the previous MI localization.Conclusions. The risk of clinical undesirable events and LV remodeling in patients with MI with ST segment elevation depends on their anamnesis, infarction localization and clinical course of the disease and also on several biochemical indicesДослідження присвячене актуальному питанню кардіології – визначенню прогнозу хворих після перенесеного гострого інфаркту міокарду. Автори розглядають показники, що впливають на ризик розвитку небажаних клінічних подій та ремоделювання серця, яке є підґрунтям серцевої недостатності - частого і важкого ускладнення інфаркту міокарду. Урахування цих чинників в процесі лікування сприятиме покращенню прогнозу хворих, що перенесли інфаркт міокард

52-week results of the phase 3 randomized study comparing SB4 with reference etanercept in patients with active rheumatoid arthritis

Objective: To compare the 52-week efficacy and safety of SB4 [an etanercept biosimilar] with reference etanercept (ETN) in patients with active RA. Methods: In a phase 3, randomized, double-blind, multicentre study, patients with moderate to severe RA despite MTX treatment were randomized to receive 50 mg/week of s.c. SB4 or ETN up to week 52. Efficacy assessments included ACR response rates, 28-joint DAS, Simplified and Clinical Disease Activity Indices and changes in the modified total Sharp score (mTSS). Safety and immunogenicity were also evaluated. Results: A total of 596 patients were randomized to receive either SB4 (n = 299) or ETN (n = 297) and 505 (84.7%) patients completed 52 weeks of the study. At week 52, the ACR20 response rates in the per-protocol set were comparable between SB4 (80.8%) and ETN (81.5%). All efficacy results were comparable between the two groups and they were maintained up to week 52. Radiographic progression was also comparable and the change from baseline in the mTSS was 0.45 for SB4 and 0.74 for ETN. The safety profile of SB4 was similar to that of ETN and the incidence of anti-drug antibody development up to week 52 was 1.0 and 13.2% in the SB4 and ETN groups, respectively. Conclusion: Efficacy including radiographic progression was comparable between SB4 and ETN up to week 52. SB4 was well tolerated and had a similar safety profile to that of ETN. Trial registration number: ClinicalTrials.gov NCT01895309, EudraCT 2012-005026-30

The use of the CNIC-Polypill in real-life clinical practice: opportunities and challenges in patients at very high risk of atherosclerotic cardiovascular disease – expert panel meeting report

Although the cardiovascular (CV) polypill concept is not new and several guidelines state that a CV polypill should be considered an integral part of a comprehensive CV disease (CVD) prevention strategy, there are still some barriers to its implementation in the real-world setting, mainly in secondary CV prevention. As the CNIC-polypill is the only one approved for secondary CV prevention in patients with atherosclerotic CVD in 27 countries worldwide, a panel of four discussants and 30 participants from 18 countries conveyed in a virtual meeting on April 21, 2022, to discuss key clinical questions regarding the practical use of the CNIC-Polypill and barriers to its implementation. Data presented showed that, although the use of the CV polypill is not explicitly mentioned in the current 2021 European Society of Cardiology guidelines on CVD prevention, it may be used in any patient for secondary CVD prevention tolerating all their components to improve outcomes through different aspects. The favourable results of the Secondary Prevention of Cardiovascular Disease in the Elderly (SECURE) trial now reinforce this recommendation. The panellists presented algorithms on how to switch from any baseline regimen when starting treatment with the CNIC-polypill in different situations, including patients with hypertension, dyslipidaemia, and a previous CV event; at discharge after a cardiovascular event; in chronic ischemic conditions; and in cases of polypharmacy. The panellists and expert discussants did agree that available studies conducted so far with the CNIC-polypill demonstrate that it is as efficacious as the monocomponents, equipotent drugs, or other therapies; reduces the risk of experiencing recurrent major CV events; improves medication adherence; reduces health care costs and resources compared to patients treated with loose drugs; and the patients prefer it over the multipill strategy. In conclusion, the data presented by the participants provided the evidence behind the use of the CNIC-polypill to help fulfil the goal of encouraging its adoption by physicians.info:eu-repo/semantics/publishedVersio

A phase III randomised, double-blind, parallel-group study comparing SB4 with etanercept reference product in patients with active rheumatoid arthritis despite methotrexate therapy

Objectives: To compare the efficacy and safety of SB4 (an etanercept biosimilar) with reference product etanercept (ETN) in patients with moderate to severe rheumatoid arthritis (RA) despite methotrexate (MTX) therapy. Methods: This is a phase III, randomised, double-blind, parallel-group, multicentre study with a 24-week primary endpoint. Patients with moderate to severe RA despite MTX treatment were randomised to receive weekly dose of 50 mg of subcutaneous SB4 or ETN. The primary endpoint was the American College of Rheumatology 20% (ACR20) response at week 24. Other efficacy endpoints as well as safety, immunogenicity and pharmacokinetic parameters were also measured. Results: 596 patients were randomised to either SB4 (N=299) or ETN (N=297). The ACR20 response rate at week 24 in the per-protocol set was 78.1% for SB4 and 80.3% for ETN. The 95% CI of the adjusted treatment difference was -9.41% to 4.98%, which is completely contained within the predefined equivalence margin of -15% to 15%, indicating therapeutic equivalence between SB4 and ETN. Other efficacy endpoints and pharmacokinetic endpoints were comparable. The incidence of treatment-emergent adverse events was comparable (55.2% vs 58.2%), and the incidence of antidrug antibody development up to week 24 was lower in SB4 compared with ETN (0.7% vs 13.1%). Conclusions: SB4 was shown to be equivalent with ETN in terms of efficacy at week 24. SB4 was well tolerated with a lower immunogenicity profile. The safety profile of SB4 was comparable with that of ETN

Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes

BACKGROUND The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown. METHODS We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy. RESULTS In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P<0.001 for noninferiority) but was not superior to placebo with respect to efficacy (P=0.06 for superiority). The rates of death from cardiovascular causes, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, hospitalization for heart failure, and hospitalization for acute coronary syndrome, and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the two groups. CONCLUSIONS Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo. (Funded by Amylin Pharmaceuticals; EXSCEL ClinicalTrials.gov number, NCT01144338.

Ertugliflozin and Slope of Chronic eGFR: Prespecified Analyses from the Randomized VERTIS CV Trial

Background and objectives A reduction in the rate of eGFR decline, with preservation of $0.75 ml/min per 1.73 m2 per year, has been proposed as a surrogate for kidney disease progression. We report results from prespecified analyses assessing effects of ertugliflozin versus placebo on eGFR slope from the eValuation of ERTugliflozin effIcacy and Safety CardioVascular outcomes (VERTIS CV) trial (NCT01986881). Design, setting, participants, & measurements Patients with type 2 diabetes mellitus and established atherosclerotic cardiovascular disease were randomized to placebo, ertugliflozin 5 mg, and ertugliflozin 15 mg (1:1:1). The analyses compared the effect of ertugliflozin (pooled doses, n55499) versus placebo (n52747) on eGFR slope per week and per year by random coefficient models. Study periods (weeks 0–6 and weeks 6–52) and total and chronic slopes (week 0 or week 6 to weeks 104, 156, 208, and 260) were modeled separately and by baseline kidney status. Results In the overall population, for weeks 0–6, the least squares mean eGFR slopes (ml/min per 1.73 m2 per week [95% confidence interval (95% CI)]) were 20.07 (20.16 to 0.03) and 20.54 (20.61 to 20.48) for the placebo and ertugliflozin groups, respectively; the difference was 20.47 (20.59 to 20.36). During weeks 6–52, least squares mean eGFR slopes (ml/min per 1.73 m2 per year [95% CI]) were 20.12 (20.70 to 0.46) and 1.62 (1.21 to 2.02) for the placebo and ertugliflozin groups, respectively; the difference was 1.74 (1.03 to 2.45). For weeks 6–156, least squares mean eGFR slopes (ml/min per 1.73 m2 per year [95% CI]) were 21.51 (21.70 to 21.32) and 20.32 (20.45 to 20.19) for the placebo and ertugliflozin groups, respectively; the difference was 1.19 (0.95 to 1.42). During weeks 0–156, the placebo-adjusted difference in least squares mean slope was 1.06 (0.85 to 1.27). These findings were consistent by baseline kidney status. Conclusions Ertugliflozin has a favorable placebo-adjusted eGFR slope .0.75 ml/min per 1.73 m2 per year, documenting the kidney function preservation underlying the clinical benefits of ertugliflozin on kidney disease progression in patients with type 2 diabetes mellitus and atherosclerotic cardiovascular disease. Clinical Trial registry name and registration number: US National Library of Medicine, ClinicalTrials.gov NCT01986881. Date of trial registration: November 13, 2013