A Placebo-Controlled Trial of Percutaneous Coronary Intervention for Stable Angina.

BACKGROUND: Percutaneous coronary intervention (PCI) is frequently performed to reduce the symptoms of stable angina. Whether PCI relieves angina more than a placebo procedure in patients who are not receiving antianginal medication remains unknown. METHODS: We conducted a double-blind, randomized, placebo-controlled trial of PCI in patients with stable angina. Patients stopped all antianginal medications and underwent a 2-week symptom assessment phase before randomization. Patients were then randomly assigned in a 1:1 ratio to undergo PCI or a placebo procedure and were followed for 12 weeks. The primary end point was the angina symptom score, which was calculated daily on the basis of the number of angina episodes that occurred on a given day, the number of antianginal medications prescribed on that day, and clinical events, including the occurrence of unblinding owing to unacceptable angina or acute coronary syndrome or death. Scores range from 0 to 79, with higher scores indicating worse health status with respect to angina. RESULTS: A total of 301 patients underwent randomization: 151 to the PCI group and 150 to the placebo group. The mean (±SD) age was 64±9 years, and 79% were men. Ischemia was present in one cardiac territory in 242 patients (80%), in two territories in 52 patients (17%), and in three territories in 7 patients (2%). In the target vessels, the median fractional flow reserve was 0.63 (interquartile range, 0.49 to 0.75), and the median instantaneous wave-free ratio was 0.78 (interquartile range, 0.55 to 0.87). At the 12-week follow-up, the mean angina symptom score was 2.9 in the PCI group and 5.6 in the placebo group (odds ratio, 2.21; 95% confidence interval, 1.41 to 3.47; P<0.001). One patient in the placebo group had unacceptable angina leading to unblinding. Acute coronary syndromes occurred in 4 patients in the PCI group and in 6 patients in the placebo group. CONCLUSIONS: Among patients with stable angina who were receiving little or no antianginal medication and had objective evidence of ischemia, PCI resulted in a lower angina symptom score than a placebo procedure, indicating a better health status with respect to angina. (Funded by the National Institute for Health and Care Research Imperial Biomedical Research Centre and others; ORBITA-2 ClinicalTrials.gov number, NCT03742050.).

Coronary sinus reducer for the treatment of refractory angina (ORBITA-COSMIC): a randomised, placebo-controlled trial.

BACKGROUND: The coronary sinus reducer (CSR) is proposed to reduce angina in patients with stable coronary artery disease by improving myocardial perfusion. We aimed to measure its efficacy, compared with placebo, on myocardial ischaemia reduction and symptom improvement. METHODS: ORBITA-COSMIC was a double-blind, randomised, placebo-controlled trial conducted at six UK hospitals. Patients aged 18 years or older with angina, stable coronary artery disease, ischaemia, and no further options for treatment were eligible. All patients completed a quantitative adenosine-stress perfusion cardiac magnetic resonance scan, symptom and quality-of-life questionnaires, and a treadmill exercise test before entering a 2-week symptom assessment phase, in which patients reported their angina symptoms using a smartphone application (ORBITA-app). Patients were randomly assigned (1:1) to receive either CSR or placebo. Both participants and investigators were masked to study assignment. After the CSR implantation or placebo procedure, patients entered a 6-month blinded follow-up phase in which they reported their daily symptoms in the ORBITA-app. At 6 months, all assessments were repeated. The primary outcome was myocardial blood flow in segments designated ischaemic at enrolment during the adenosine-stress perfusion cardiac magnetic resonance scan. The primary symptom outcome was the number of daily angina episodes. Analysis was done by intention-to-treat and followed Bayesian methodology. The study is registered with ClinicalTrials.gov, NCT04892537, and completed. FINDINGS: Between May 26, 2021, and June 28, 2023, 61 patients were enrolled, of whom 51 (44 [86%] male; seven [14%] female) were randomly assigned to either the CSR group (n=25) or the placebo group (n=26). Of these, 50 patients were included in the intention-to-treat analysis (24 in the CSR group and 26 in the placebo group). 454 (57%) of 800 imaged cardiac segments were ischaemic at enrolment, with a median stress myocardial blood flow of 1·08 mL/min per g (IQR 0·77-1·41). Myocardial blood flow in ischaemic segments did not improve with CSR compared with placebo (difference 0·06 mL/min per g [95% CrI -0·09 to 0·20]; Pr(Benefit)=78·8%). The number of daily angina episodes was reduced with CSR compared with placebo (OR 1·40 [95% CrI 1·08 to 1·83]; Pr(Benefit)=99·4%). There were two CSR embolisation events in the CSR group, and no acute coronary syndrome events or deaths in either group. INTERPRETATION: ORBITA-COSMIC found no evidence that the CSR improved transmural myocardial perfusion, but the CSR did improve angina compared with placebo. These findings provide evidence for the use of CSR as a further antianginal option for patients with stable coronary artery disease. FUNDING: Medical Research Council, Imperial College Healthcare Charity, National Institute for Health and Care Research Imperial Biomedical Research Centre, St Mary's Coronary Flow Trust, British Heart Foundation.

The impact of statins treatments for plaque characteristics in stable angina pectoris patients with very low and high low-density lipoprotein cholesterol levels: an intracoronary optical coherence tomography study.

Low-density lipoprotein cholesterol (LDL-C) levels are recommended according to the patient's risk factors based on guidelines. In patients achieving low LDL-C levels, the need for statins is uncertain, and the plaque characteristics of patients not treated with statins are unclear. In addition, the difference in plaque characteristics with and without statins is unclear in similarly high LDL levels. We evaluate the impact of statins on plaque characteristics on optical coherence tomography (OCT) in patients with very low LDL-C levels and high LDL-C levels. A total of 173 stable angina pectoris patients with 173 lesions undergoing OCT before percutaneous coronary intervention were evaluated. We divided the LDL-C levels into three groups: < 70 mg/dL (n = 48), 70 mg/dL ≤ LDL-C < 100 mg/dL (n = 71), and ≥ 100 mg/dL (n = 54). Among patients with LDL-C < 70 mg/dL, patients not treated with statins showed a significantly higher C-reactive protein level (0.27 ± 0.22 mg/dL vs. 0.15 ± 0.19 mg/dL, p = 0.049), and higher incidence of thin-cap fibroatheromas (TCFAs; 44% [7/16] vs. 13% [4/32], p = 0.021) than those treated with statins. Among patients with LDL-C level ≥ 100 mg/dL, patients treated with statins showed a significantly higher prevalence of familial hypercholesterolemia (FH) (38% [6/16] vs. 5% [2/38], p = 0.004), lower incidence of TCFAs (6% [1/16] vs. 39% [15/38], p = 0.013), healed plaques (13% [2/16] vs. 47% [18/38], p = 0.015), and higher incidence of fibrous plaques (75% [12/16] vs. 42% [16/38], p = 0.027) than patients not treated with statins. While patients achieved a low LDL-C, patients not treated with statins had high plaque vulnerability and high systemic inflammation. While patients had a high LDL-C level with a high prevalence of FH, patients treated with statins had stable plaque characteristics.

Study on the Therapeutic Value of Shexiang Tongxin Dropping Pills in Patients with Stable Angina Pectoris of Coronary Heart Disease Complicated with Cognitive Impairment.

BACKGROUND: There is a pressing need to identify pharmaceuticals that are both safe and efficacious, with lower toxicity, for the treatment of stable angina pectoris in individuals suffering from coronary heart disease. The aim of this paper is to explore the therapeutic value of Shexiang Tongxin Dropping Pills in patients with stable angina pectoris of coronary heart disease complicated with cognitive impairment. METHODS: 200 patients with stable angina pectoris combined with cognitive dysfunction and coronary heart disease admitted to our hospital from January 2022 to June 2023 were retrospectively selected as the study objects. According to the treatment method, the subjects were divided into a control group and a study group, with 100 cases in each group. The control group received conventional oral Western medicine, and the study group underwent treatment with Shexiang Tongxin Dropping Pills in addition to traditional Western medicine. The course of treatment was eight weeks. The enhancement in angina pectoris, cognitive function level, self-care ability, and clinical efficacy of both groups were assessed by comparing the conditions before and after the treatment. RESULTS: After treatment, the frequency and duration of angina pectoris attacks in both groups were significantly lower than before, and the study group was lower than the control group (p < 0.05). The Montreal Cognitive Assessment (MoCA) score of both groups was higher than before, and the score of the study group was significantly higher than that of the control group (p < 0.05). Neuropsychiatric Inventory (NPI) scores in both groups were significantly lower than before, and the scores of the study group were significantly lower than those of the control group (p < 0.05). Traditional Chinese Medicine (TCM) syndrome scores in both groups were significantly lower than before, and the scores of the study group were significantly lower than those of the control group (p < 0.05). After treatment, the total effective rate of the control group and the study group was 81.00% and 93.00%, respectively, and the total clinical effective rate of the study group was significantly higher than that of the control group (p < 0.05). CONCLUSION: Shexiang Tongxin Dropping Pills can effectively reduce the incidence of angina pectoris in patients with stable angina pectoris complicated with coronary heart disease and cognitive dysfunction. It can also regulate the patient's neurological function, improve their cognitive level, and significantly improve clinical efficacy.

[Network Meta-analysis of Chinese medicine injection combined with conventional western medicine in treatment of stable angina pectoris].

This study aimed to systematically evaluate the efficacy and safety of different Chinese medicine injections combined with conventional western medicine for stable angina pectoris. PubMed, Cochrane Library, EMbase, Web of Science, CNKI, Wanfang, VIP, and SinoMed were searched to collect randomized controlled trial(RCT) of Chinese medicine injection combined with conventio-nal western medicine in the treatment of stable angina pectoris from the inception of the databases to July 8, 2022. Two researchers independently screened the literature, extracted the data, and evaluated the risk of bias of the included studies. Stata 15.1 was used for network Meta-analysis. A total of 52 RCTs were included, involving 4 828 patients treated by 9 Chinese medicine injections(Danhong Injection, Salvia Miltiorrhiza Polyphenol Hydrochloride Injection, Tanshinone Sodium Ⅱ_A Sulfonate Injection, Salvia Miltiorrhiza Ligustrazine Injection, Dazhu Hongjingtian Injection, Puerarin Injection, Safflower Yellow Pigment Injection, Shenmai Injection and Xuesaitong Injection). The network Meta-analysis showed that:(1)in terms of improving the efficacy of angina pectoris, the surface under the cumulative ranking curve(SUCRA) followed the order of conventional western medicine combined with Salvia Miltiorrhiza Ligustrazine Injection>Tanshinone Sodium Ⅱ_A Sulfonate Injection>Danhong Injection>Salvia Miltiorrhiza Polyphenol Hydrochloride Injection>Xuesaitong Injection>Shenmai Injection>Puerarin Injection>Safflower Yellow Pigment Injection>Dazhu Hongjingtian Injection;(2)in terms of improving the efficacy of electrocardiogram(ECG), SUCRA followed the order of conventional western medicine combined with Salvia Miltiorrhiza Ligustrazine Injection>Puerarin Injection>Danhong Injection>Salvia Miltiorrhiza Polyphenol Hydrochloride Injection>Shenmai Injection>Xuesaitong Injection>Safflower Yellow Pigment Injection>Tanshinone Sodium Ⅱ_A Sulfonate Injection>Dazhu Hongjingtian Injection;(3)in terms of increasing high-density lipoprotein cholesterol(HDL-C), SUCRA followed the order of conventional western medicine combined with Danhong Injection>Shenmai Injection>Safflower Yellow Pigment Injection>Xuesaitong Injection>Tanshinone Sodium Ⅱ_A Sulfonate Injection>Dazhu Hongjingtian Injection;(4)in terms of lowering low-density lipoprotein cholesterol(LDL-C), SUCRA followed the order of conventional western medicine combined with Safflower Yellow Pigment Injection>Danhong Injection>Shenmai Injection>Tanshinone Sodium Ⅱ_A Sulfonate Injection>Dazhu Hongjingtian Injection>Xuesaitong Injection;(5)in terms of safety, the overall adverse reactions of Chinese medicine injection combined with conventional western medicine were less than those of the control group. Current evidence indicated that Chinese medicine injection combined with conventional western medicine could improve the curative effect of stable angina pectoris with higher safety. Limited by the number and quality of included studies, the above conclusion needed to be verified by more high-quality studies.

[Post-marketing effectiveness evaluation of traditional Chinese medicine in paradigm based on "proving efficacy, conforming standard, and exploring mechanism":a case study of Danhong Injection].

At present, new concepts, new technologies, and new methods are emerging in the field of medical research, breaking through the inherent thinking patterns and research models, and promoting the transformation of the research paradigm of traditional Chinese medicine(TCM). This paper gave a case study of clinical research in Danhong Injection in the treatment of chronic stable angina, and based on the background of the study, index evaluation model, experimental design method, blind implementation of placebo, data management system, and exploration of clinical efficacy mechanism of traditional Chinese medicine compounds under the framework of modular pharmacology, the scientific idea of "proving efficacy, conforming standard, and exploring mechanism" was used as the guideline to discuss the research model of reevaluation of the effectiveness of post-marketing TCM varieties. This paper drew a target network map of Danhong Injection in the treatment of chronic stable angina for the first time, which was composed of targeted functional modules. By combining evidence-based clinical research with modular pharmacology framework, changes in the pharmacolo-gical mechanism were finally associated with changes in clinical efficacy, and the advantages of phenotypic correlation of efficacy were explored. This study is expected to provide references for the post-marketing effectiveness evaluation and new ideas for the phenotypic pharmacological mechanism study of multi-target TCM compounds and precise treatment, thereby promoting the innovative development of TCM.

The possibilities of using beta-blocker bisoprolol in patients with stable angina with concomitant bronchial asthma.

Aim    To compare efficacy and safety of treatments with the calcium antagonist (CA) verapamil, the cardioselective ß-blocker (BB) bisoprolol, and a combination therapy with bisoprolol and amlodipine in patients with stable angina (SA) with concurrent mild and moderate, persistent bronchial asthma (BA). Material and methods    This open, prospective, randomized, comparative study included 120 patients with an IHD+BA comorbidity. Of these patients, 60 had mild persistent BA and 60 had moderate persistent BA. Each group was divided into 3 subgroup, each including 20 patients, based on the used regimen of antianginal therapy. Stepwise dose titration was performed every 2 weeks (subgroup 1 received the BB bisoprolol 2.5 mg - 5 mg - 10 mg; subgroup 2 received the CA verapamil 240 mg - 240 mg - 240 mg; subgroup 3 received bisoprolol 2.5 mg followed by the combination treatment with bisoprolol and amlodipine as a fixed combination 5+5 mg). All patients underwent a complete clinical and instrumental examination at baseline and at 2, 4, and 6 weeks of treatment. The antianginal effectivity and the effect on bronchial patency were evaluated. Results    In patients with SA and mild persistent BA, the study of external respiration function (ERF) at 2, 4, and 6 weeks of treatment did not detect any significant difference in the forced expiratory volume in 1 second (FEV1) between the treatment subgroups. In patients with SA and moderate persistent BA receiving the treatment, a significant decrease in FEV1 (р=0.022) was observed in subgroup 1 receiving bisoprolol 10 mg at 6 weeks of treatment. In subgroups 2 and 3 during the treatment, significant differences were absent. In patients with SA and mild or moderate persistent BA, the heart rate was significantly decreased in all three subgroups; however, in subgroup 2 receiving verapamil, the changes were considerably smaller than in other subgroups.Conclusion    The study results showed that the BB bisoprolol with dose titration every two weeks from 2.5 to 10 mg or the combination treatment with the BB bisoprolol and the CA amlodipine can be used as the antianginal therapy in patients with SA and mild persistent BA. The BB bisoprolol may be used in patients with SA and moderate persistent BA as the antianginal therapy, but only at doses not exceeding 5 mg to avoid the development of bronchial obstruction. The combination therapy with the BB bisoprolol 5 mg and the CA amlodipine 5 mg is indicated to enhance antianginal and vasoprotective effects.

Relation of renal function to mid-term prognosis of stable angina patients with high- or low-dose pitavastatin treatment: REAL-CAD substudy.

BACKGROUND: It has not yet been established whether higher-dose statins have beneficial effects on cardiovascular events in patients with stable coronary artery disease (CAD) and renal dysfunction. METHODS: The REAL-CAD study is a prospective, multicenter, open-label trial. As a substudy, we categorized patients by an estimated glomerular filtration rate (eGFR) as follows: eGFR ≥60 (n = 7,768); eGFR ≥45 and <60 (n = 3,176); and eGFR <45 mL/Min/1.73 m2 (n = 1,164), who were randomized to pitavastatin 4mg or 1mg therapy. The primary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, or unstable angina, and was assessed by the log-rank test and Cox proportional hazards model. RESULTS: The baseline characteristics and medications were largely well-balanced between two groups. The magnitude of low-density lipoprotein cholesterol (LDL-C) reduction at 6 months in high- and low-dose pitavastatin groups was comparable among all eGFR categories. During a median follow-up of 3.9 years, high- compared with low-dose pitavastatin significantly reduced cardiovascular events in patients with eGFR ≥60 (hazard ratio (HR) 0.73; 95% confidence interval (CI) 0.58-0.91; P = .006), and reduced but not significant for patients with eGFR ≥45 and <60 (HR 0.85; 95% CI, 0.63-1.14; P = .27) or eGFR <45 mL/Min/1.73 m2 (HR 0.90; 95% CI 0.62-1.33; P = .61). An interaction test of treatment by eGFR category was not significant (P value for interaction = .30). CONCLUSION: Higher-dose pitavastatin therapy reduced LDL levels and cardiovascular events in stable CAD patients irrespective of eGFR level, although the effect on events appeared to be numerically lower in patients with lower eGFR.

Effect of DLT-SML on Chronic Stable Angina Through Ameliorating Inflammation, Correcting Dyslipidemia, and Regulating Gut Microbiota.

ABSTRACT: Chronic stable angina (CSA) is caused by coronary atherosclerosis. The gut microbiota (GM) and their metabolite trimethylamine-N-oxide (TMAO) levels are associated with atherosclerosis. Danlou tablet (DLT) combined with Salvia miltiorrhiza ligustrazine (SML) injection has been used to treat CSA. This study aims to investigate how DLT combined with SML (DLT-SML) regulates serum lipids, inflammatory cytokines, GM community, and microbial metabolite in patients with CSA. In this study, 30 patients with CSA were enrolled in the DLT-SML group, and 10 healthy volunteers were included in the healthy control group. The patients in the DLT-SML group were subdivided as the normal total cholesterol (TC) group and high-TC group according to their serum TC level before treatment. Blood samples were collected to investigate the (1) lipid content, including triglyceride (TG), TC, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol, (2) fasting blood glucose (Glu), (3) inflammatory cytokines, including interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α), and (4) gut-derived metabolite, including lipopolysaccharides and TMAO level. GM composition was analyzed by sequencing 16S rRNA of fecal samples. Results showed that DLT-SML significantly decreased serum TG, TC, low-density lipoprotein cholesterol, IL-1ß, TNF-α, and TMAO levels of patients with CSA. DLT-SML increased the abundance of Firmicutes and decreased Proteobacteria, which were significantly lower or higher in patients with CSA, respectively, compared with the healthy control group. In particular, DLT-SML increased the microbial diversity and decreased Firmicutes/Bacteroidetes ratio of patients with high-TC. The abundance of Sarcina, Anaerostipes, Streptococcus, Weissella, and Erysipelatoclostridium was decreased, whereas Romboutsia, Faecalibacterium, and Subdoligranulum were increased by DLT-SML treatment in patients with CSA. These findings indicated that DLT-SML improved patients with CSA by ameliorating dyslipidemia profile, decreasing the circulating inflammatory cytokines, and regulating the GM composition and their metabolites.

Diagnosis and Management of Stable Angina: A Review.

IMPORTANCE: Nearly 10 million US adults experience stable angina, which occurs when myocardial oxygen supply does not meet demand, resulting in myocardial ischemia. Stable angina is associated with an average annual risk of 3% to 4% for myocardial infarction or death. Diagnostic tests and medical therapies for stable angina have evolved over the last decade with a better understanding of the optimal use of coronary revascularization. OBSERVATIONS: Coronary computed tomographic angiography is a first-line diagnostic test in the evaluation of patients with stable angina due to higher sensitivity and comparable specificity compared with imaging-based stress testing. Moreover, coronary computed tomographic angiography allows detection of nonobstructive atherosclerosis that would not be identified with other noninvasive imaging modalities, improving risk assessment and potentially triggering more appropriate allocation of preventive therapies. Novel therapies treating lipids (proprotein convertase subtilisin/kexin type 9 inhibitors, ezetimibe, and icosapent ethyl) and type 2 diabetes (sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 receptor agonists) have improved cardiovascular outcomes in patients with stable ischemic heart disease when added to usual care. Randomized clinical trials showed no improvement in the rates of mortality or myocardial infarction with revascularization (largely by percutaneous coronary intervention) compared with optimal medical therapy alone, even in the setting of moderate to severe ischemia. In contrast, revascularization provides a meaningful benefit on angina and quality of life compared with antianginal therapies. Measures of the effect of angina on a patient's quality of life should be integrated into the clinic encounter to assist with the decision to proceed with revascularization. CONCLUSIONS AND RELEVANCE: For patients with stable angina, emphasis should be placed on optimizing lifestyle factors and preventive medications such as lipid-lowering and antiplatelet agents to reduce the risk for cardiovascular events and death. Antianginal medications, such as ß-blockers, nitrates, or calcium channel blockers, should be initiated to improve angina symptoms. Revascularization with percutaneous coronary intervention should be reserved for patients in whom angina symptoms negatively influence quality of life, generally after a trial of antianginal medical therapy. Shared decision-making with an informed patient is important for effective treatment of stable angina.

Efficacy of trimetazidine - an inhibitor of free fatty acids oxidation in the treatment of patients with stable angina pectoris and heart failure.

Aim      To evaluate efficacy of modified-release trimetazidine (TMZ) included into the standard therapy for patients with stable angina and chronic heart failure (CHF) as a part of a subgroup analysis in the PERSPECTIVE study.Material and methods  The study included 806 patients: group 1 (n=691), patients receiving a standard therapy and modified-release TMZ (TMZ group); and group 2 (n=115), patients receiving a standard therapy (control group). Total duration of the study was 12 months.Results In the TMZ group, the weekly number of angina attacks decreased by 41.9% (p<0.0001) in 2 months and by 69.6 % (from baseline, р<0.0001) in 12 months, and the frequency of nitroglycerine dosing decreased by 40.8 % (р<0.0001) and 67.7 % (р<0.0001), respectively. In the control group, the respective values did not change. In the TMZ group compared to the control group, the QT interval was shorter (7.9 %; р<0.05), the left ventricular (LV) end-systolic dimension was reduced (13.4 %; р<0.01), interventricular septal thickness and LV posterior wall thickness were decreased (9.5 %; р<0.01 and 12.2 %; р<0.01, respectively), and the ejection fraction was increased (11.4; р<0.05). Following the TMZ treatment, the leukocyte count in peripheral blood was decreased (5.3 %; р<0.01) and the serum concentration of high-sensitivity C-reactive protein was decreased (30.7 %; р<0.01) vs. increases of these indexes in the control group (17.9 %; р<0.05 and 17.8 %; р<0.05, respectively). The proportion of patients hospitalized for exacerbation of CHF or angina for 12 months was 8.6 % in the TMZ group and 15.7 % in the control group (p=0,001).Conclusion      In patients with stable angina and CHF, inclusion of modified-release TMZ into the standard therapy decreases the number of angina attacks, reduces the activity of inflammatory factors, and improves the course of disease.

The effect of rivaroxaban low doses on the stable angina of the II-III functional class clinical manifestations and the quality of life in patients with ischemic heart disease.

Aim      To evaluate the effect of low-dose rivaroxaban on quality of life of patients and clinical manifestations of functional class (FC) II-III stable angina.Material and methods  26 patients with ischemic heart disease (IHD) with FC II-III stable angina, who were newly prescribed rivaroxaban 2.5 mg twice a day in combination with acetylsalicylic acid 75-100 mg, were followed for 10 weeks. During the first (before the beginning of treatment) and the last weeks of study, patients kept diaries, in which they reported angina attacks and short-acting nitrate intake, filled in an angina questionnaire (SAQ), and underwent electrocardiogram (ECG) Holter monitoring (HM).Results The treatment was associated with decreases in the frequency of angina attacks (by 19.5 %; р=0.027) and the number of taken short-acting nitrate pills (by 17.1 %; р=0.021) and an improvement of quality of life according to stability scales (р=0.042). Data from ECG HM showed decreases in the number and duration of ischemic episodes (p≤0.05).Conclusion      The treatment of IHD patients with rivaroxaban 2.5 mg twice a day in combination with acetylsalicylic acid 75-100 mg for 2 mos. was associated with decreased frequency of angina attacks, reduced requirement for short-acting nitrate, and with improvement of quality of life.

Dobutamine Stress Echocardiography Ischemia as a Predictor of the Placebo-Controlled Efficacy of Percutaneous Coronary Intervention in Stable Coronary Artery Disease: The Stress Echocardiography-Stratified Analysis of ORBITA.

BACKGROUND: Dobutamine stress echocardiography is widely used to test for ischemia in patients with stable coronary artery disease. In this analysis, we studied the ability of the prerandomization stress echocardiography score to predict the placebo-controlled efficacy of percutaneous coronary intervention (PCI) within the ORBITA trial (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina). METHODS: One hundred eighty-three patients underwent dobutamine stress echocardiography before randomization. The stress echocardiography score is broadly the number of segments abnormal at peak stress, with akinetic segments counting double and dyskinetic segments counting triple. The ability of prerandomization stress echocardiography to predict the placebo-controlled effect of PCI on response variables was tested by using regression modeling. RESULTS: At prerandomization, the stress echocardiography score was 1.56±1.77 in the PCI arm (n=98) and 1.61±1.73 in the placebo arm (n=85). There was a detectable interaction between prerandomization stress echocardiography score and the effect of PCI on angina frequency score with a larger placebo-controlled effect in patients with the highest stress echocardiography score (Pinteraction=0.031). With our sample size, we were unable to detect an interaction between stress echocardiography score and any other patient-reported response variables: freedom from angina (Pinteraction=0.116), physical limitation (Pinteraction=0.461), quality of life (Pinteraction=0.689), EuroQOL 5 quality-of-life score (Pinteraction=0.789), or between stress echocardiography score and physician-assessed Canadian Cardiovascular Society angina class (Pinteraction=0.693), and treadmill exercise time (Pinteraction=0.426). CONCLUSIONS: The degree of ischemia assessed by dobutamine stress echocardiography predicts the placebo-controlled efficacy of PCI on patient-reported angina frequency. The greater the downstream stress echocardiography abnormality caused by a stenosis, the greater the reduction in symptoms from PCI. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02062593.

Prevalence of angina and use of medical therapy among US adults: A nationally representative estimate.

Recent results from the ISCHEMIA trial highlight the importance of medical management for patients with stable ischemic heart disease. We determine the prevalence of angina in the United States, as well as the use of first-line goal directed therapy by US patients with angina. We used individual patient level data from the National Health and Nutrition Examination Survey (NHANES), 2007-2016. Using the complex survey weights, we create projections for the US population with angina as well as those using ß-blockers, antiplatelet agents, or statins-3 first-line medications for patients with angina. Among adults ≥40 years old, 4,469,934 US adults are estimated to have physician-diagnosed angina. Of the patients with angina, 2,757,171 (61.7%) were on ß-blockers, 2,984,902 (66.8%) were on statins, and 2,433,088 (54.4%) were on any antiplatelet medication; 1,457,983 patients were on all 3 medications, for an overall proportion of 32.6% of angina patients taking all three first-line medications in the United States. While the prevalence of angina in the US is high, the use of goal-directed medical therapy remains low. Strategies to improve the use of medications for preventing secondary events are urgently needed.

New potential modulators of CYP4F2 enzyme activity in angina pectoris: hsa-miR-24-3p and hsa-miR-34a-5p.

Purpose: To find an association of relative expression of hsa-miR-24-3p and hsa-miR-34a-5p molecules and CYP4F2 enzyme activity in blood plasma of stable angina pectoris (AP) patients'.Materials and Methods: MiRNA gene expression analysis was performed on total RNA extracted from blood plasma, using quantitative real-time polymerase chain reaction. CYP4F2 enzyme levels were determined using commercial ELISA kit. In total, 32 AP and 15 control samples were examined.Results: The relative expression of hsa-miR-24-3p and hsa-miR-34a-5p was upregulated by 4.4 (p = 0.0001) and 3.8 (p = 0.005) -fold in AP patient's blood plasma compared to control subjects. CYP4F2 enzyme level in blood plasma were 2.1 (p = 0.001) times lower in AP patients. Circulating hsa-miR-24-3p was negatively associated with CYP4F2 enzyme level (Spearman correlation coefficient rank r= -0.32; p = 0.03). Moreover, patients that were taking atorvastatin, had 1.5 (p = 0.04) times higher hsa-miR-24-3p expression in blood plasma.Conclusions. Our data suggest that hsa-miR-24-3p might have an effect on CYP4F2 activity during atherosclerosis.

Low Response to Clopidogrel in Coronary Artery Disease.

BACKGROUND: In patients with coronary artery disease, cardiovascular mortality and other acute events showed a clear correlation with risk factors and biomarkers including platelet activation. STUDY QUESTION OF THIS RESEARCH: Which was the incidence of low response to clopidogrel and its correlation with risk factors and biomarkers in coronary artery disease? STUDY DESIGN: Four hundred patients (pts) with coronary artery disease-stable angina (SA) and acute coronary syndrome-were divided into 8 groups of study, consistent with low response to clopidogrel and the type of coronary artery disease. Low response to clopidogrel-defined as adenosine diphosphate test-ADP-test of >46 U by multiple electrode platelet aggregometry was evaluated in correlation with cardiovascular risk factors and biomarkers of oxidative stress, endothelial dysfunction, hypercoagulability, high platelet reactivity. RESULTS: In coronary artery disease, low response to clopidogrel significantly correlated with older than 65 years, smoking, hypertension, diabetes mellitus, body mass index of >25, previous aspirin treatment (P < 0.05), high value of total and low-density lipoprotein cholesterol, low value of high-density lipoprotein cholesterol, low response to aspirin, high mean platelets volume and von Willebrand factor activity, low flow-mediated vasodilatation, total antioxidant status (P < 0.01) and only in patients with SA of male gender (P < 0.01). The incidence of other hypercoagulability biomarkers, such as reduced values of S protein, C protein, antithrombin III, and V Factor Leiden resistance to activated protein C, was very low and not correlated with low response to clopidogrel. CONCLUSIONS: In coronary artery disease, low response to clopidogrel significantly correlated with the most of old cardiovascular risk factors, with previous aspirin treatment, low response to aspirin, higher mean platelets volume, higher von Willebrand factor activity, lower flow-mediated vasodilatation, and lower total antioxidant status values and only in patients with SA of male gender.

[Efficacy and Safety of Combined Treament with Ivabradine and Metoprolol in Patients with Stable Angina Pectoris - a Systematic Review].

This article presents results of a systematic review, which was designed for evaluating the effect of combination treatment with ivabradine and metoprolol on heart rate, frequency of angina attacks, frequency of using short-acting nitrates, and angina severity. The analysis included data from three large observational studies on efficacy of the ivabradine and metoprolol tartrate combination in patients with chronic angina. Results of the analysis supported the efficacy of the metoprolol and ivabradine combination in clinical practice, which provided effective decreases in the heart rate, frequency of angina attacks, requirement for short-acting nitrates, and alleviation of angina severity. The studies demonstrated good tolerability of this treatment.

Practical Recommendations for the Diagnosis and Medical Management of Stable Angina: An Expert Panel Consensus.

Stable angina affects a significant number of coronary artery disease patients, impairing their quality of life and worsening their prognosis. It manifests even despite a history of revascularization and is often poorly controlled with drug therapy. Comorbid conditions are frequently encountered in coronary artery disease patients, affecting their prognosis and rendering the diagnosis and management of angina more challenging. In this article, derived by an expert panel meeting, we attempt a practical approach to stable angina, focusing on symptomatic patients subjected to previous coronary revascularization or not suitable for revascularization and providing handy diagnostic and therapeutic algorithms and comorbidity-adjusted therapeutic approaches in accordance with existing evidence, current recommendations, and locally available therapeutic options.

Ivabradine drug utilization study in five European countries: A multinational, retrospective, observational study to assess effectiveness of risk-minimization measures.

PURPOSE: This drug utilization study of ivabradine evaluated prescriber compliance with the new risk minimization measures (RMMs), communicated starting 2014 following preliminary results from the SIGNIFY study. METHODS: This was a multinational (five European countries) chart review study with two study periods: pre-RMM and post-RMM. Patients initiating ivabradine for chronic stable angina pectoris in routine clinical practice were identified across general practitioners and specialists. The primary outcome analysis evaluated the compliance with the new RMMs, ie, use in patients with a heart rate greater than or equal to 70 bpm at initiation, no doses higher than those recommended in the summary of product characteristics (SmPC) at initiation and during 6 months of follow-up, and no concomitant use of verapamil or diltiazem. RESULTS: Overall, 711 and 506 eligible patients were included in the pre-RMM and post-RMM periods, respectively. The percentage of patients prescribed ivabradine according to the new RMMs increased significantly in the post-RMM period (70.6% and 78.4% in the pre- and post-RMM periods respectively; P value = .0035). The compliance to RMMs increased for all the criteria assessed independently: the proportions of patients with (a) heart rate ≥ 70 bpm at initiation (79.4% and 85.2%, respectively; P value = .0141), (b) no dose higher than the SmPC doses at initiation and during follow-up (92.8% and 94.1%, respectively; P value = .3957), and (c) no concomitance with verapamil or diltiazem (96.1% and 99.2%, respectively; P value = .0007). CONCLUSIONS: The RMMs for ivabradine were well implemented across the five participating European countries confirming a favorable benefit-risk balance of ivabradine in chronic stable angina pectoris.

Multiple myocardial bridges associated with left-ventricular dysfunction, intermittent left bundle branch block, and cardiac memory: A case report.

Myocardial bridges are a congenital anomaly in which a segment of the coronary artery takes a "tunneled" intramuscular course. Few reports have associated myocardial bridges with left-ventricular dysfunction in patients with ischemia. Intermittent left bundle branch block is a conduction disturbance that has been described to be associated with myocardial bridges and cardiac memory. This study reports unusual associations of multiple myocardial bridges, angina, left-ventricular dysfunction, intermittent left bundle branch block, and cardiac memory.