Traditional Chinese Medicine in the prevention and treatment of stable angina pectoris in patients with coronary heart disease based on the theory of "phlegm and blood stasis" under guidance of evidence-based medicine: a prospective cohort study.

OBJECTIVE: To ascertain whether continuous treatment with Traditional Chinese Medicine (TCM) combined with standardized drug therapy from Western Medicine can further reduce the incidence of cardiovascular events in patients with coronary heart disease and angina and reduce the incidence of angina pectoris in patients with coronary heart disease. METHODS: A multicenter, prospective cohort study of 1042 patients in 22 hospitals was conducted. A total of 423 patients with angina pectoris were treated with standardized Western Medicine alone (control group) and 619 with a combination of Chinese and Western Medicine (exposure group). The two groups underwent follow-up for 1 year to establish whether there was any improvement in the incidence of cardiovascular events or change in the curative effect. RESULTS: The incidence of primary endpoint events in the combined-exposure group decreased by 0.45% (P > 0.05) and the incidence of secondary terminal events decreased by 5.25% in comparison with the control group (P < 0.05). The total angina pectoris score clearly decreased in the Western Medicine group over the first 6 months, but the decline was more apparent in the combined-exposure group. CONCLUSION: Compared with treatment using standardized Western Medicine alone, providing TCM combined with Western medical treatment reduced the incidence of cardiovascular events in patients with stable angina pectoris (grade Ⅱ endpoint) and effectively improved the curative effect.

The role of polysaccharide peptide of Ganoderma lucidum as a potent antioxidant against atherosclerosis in high risk and stable angina patients.

OBJECTIVES: Antioxidants can reduce oxidative radicals that affect the early phase of atherogenesis, that is endothelial dysfunction. Polysaccharide Peptide (PsP) derived from Ganoderma lucidum has an active substance in the form of ß-glucan. Previous studies have proven the PsP of Ganoderma lucidum as an effective antioxidant in atherosclerotic rats and shows no toxicity in animal model. This study aims to prove the effect of PsP as potent antioxidant in high risk and stable angina patients. METHOD: This is a clinical trial conducted to 37 high risk and 34 stable angina patients, which were determined based on ESC Stable CAD Guidelines and Framingham risk score, with pre and post test design without control group. The parameters are superoxide dimustase (SOD) and malondialdehyde (MDA) concentration, circulating endothelial cell (CEC) and endothelial progenitor cell (EPC) counts. The patients were given PsP 750mg/day in 3 divided dose for 90days. Paired t-test was performed for normally distributed data, and Wilcoxon test for not normally distributed data, and significant level of p≤0,05. RESULTS: SOD level in high risk patients slightly increased but not statistically significant with p=0,22. Level of SOD in stable angina group significantly increased with p=0,001. MDA concentration significantly reduced in high risk and stable angina patients with p=0.000. CEC significantly reduced both in high risk and stable angina patients, with p=0.000 in both groups. EPC count significantly reduced in high risk and stable angina with p=0.000. CONCLUSION: PsP of Ganoderma lucidum is a potent antioxidant against pathogenesis of atherosclerosis in stable angina and high risk patients.

Ranolazine for stable angina pectoris.

BACKGROUND: Stable angina pectoris is a chronic medical condition with significant impact on mortality and quality of life; it can be macrovascular or microvascular in origin. Ranolazine is a second-line anti-anginal drug approved for use in people with stable angina. However, the effects of ranolazine for people with angina are considered to be modest, with uncertain clinical relevance. OBJECTIVES: To assess the effects of ranolazine on cardiovascular and non-cardiovascular mortality, all-cause mortality, quality of life, acute myocardial infarction incidence, angina episodes frequency and adverse events incidence in stable angina patients, used either as monotherapy or as add-on therapy, and compared to placebo or any other anti-anginal agent. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase and the Conference Proceedings Citation Index - Science in February 2016, as well as regional databases and trials registers. We also screened reference lists. SELECTION CRITERIA: Randomised controlled trials (RCTs) which directly compared the effects of ranolazine versus placebo or other anti-anginals in people with stable angina pectoris were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies, extracted data and assessed risk of bias. Estimates of treatment effects were calculated using risk ratios (RR), mean differences (MD) and standardised mean differences (SMD) with 95% confidence intervals (CI) using a fixed-effect model. Where we found statistically significant heterogeneity (Chi² P < 0.10), we used a random-effects model for pooling estimates. Meta-analysis was not performed where we found considerable heterogeneity (I² ≥ 75%). We used GRADE criteria to assess evidence quality and the GRADE profiler (GRADEpro GDT) to import data from Review Manager 5.3 to create 'Summary of findings' tables. MAIN RESULTS: We included 17 RCTs (9975 participants, mean age 63.3 years). We found very limited (or no) data to inform most planned comparisons. Summary data were used to inform comparison of ranolazine versus placebo. Overall, risk of bias was assessed as unclear.For add-on ranolazine compared to placebo, no data were available to estimate cardiovascular and non-cardiovascular mortality. We found uncertainty about the effect of ranolazine on: all-cause mortality (1000 mg twice daily, RR 0.83, 95% CI 0.26 to 2.71; 3 studies, 2053 participants; low quality evidence); quality of life (any dose, SMD 0.25, 95% CI -0.01 to 0.52; 4 studies, 1563 participants; I² = 73%; moderate quality evidence); and incidence of non-fatal acute myocardial infarction (AMI) (1000mg twice daily, RR 0.40, 95% CI 0.08 to 2.07; 2 studies, 1509 participants; low quality evidence). Add-on ranolazine 1000 mg twice daily reduced the fervour of angina episodes (MD -0.66, 95% CI -0.97 to -0.35; 3 studies, 2004 participants; I² = 39%; moderate quality evidence) but increased the risk of non-serious adverse events (RR 1.22, 95% CI 1.06 to 1.40; 3 studies, 2053 participants; moderate quality evidence).For ranolazine as monotherapy compared to placebo, we found uncertain effect on cardiovascular mortality (1000 mg twice daily, RR 1.03, 95% CI 0.56 to 1.88; 1 study, 2604 participants; low quality evidence). No data were available to estimate non-cardiovascular mortality. We also found an uncertain effect on all-cause mortality for ranolazine (1000 mg twice daily, RR 1.00, 95% CI 0.81 to 1.25; 3 studies, 6249 participants; low quality evidence), quality of life (1000 mg twice daily, MD 0.28, 95% CI -1.57 to 2.13; 3 studies, 2254 participants; moderate quality evidence), non-fatal AMI incidence (any dose, RR 0.88, 95% CI 0.69 to 1.12; 3 studies, 2983 participants; I² = 50%; low quality evidence), and frequency of angina episodes (any dose, MD 0.08, 95% CI -0.85 to 1.01; 2 studies, 402 participants; low quality evidence). We found an increased risk for non-serious adverse events associated with ranolazine (any dose, RR 1.50, 95% CI 1.12 to 2.00; 3 studies, 947 participants; very low quality evidence). AUTHORS' CONCLUSIONS: We found very low quality evidence showing that people with stable angina who received ranolazine as monotherapy had increased risk of presenting non-serious adverse events compared to those given placebo. We found low quality evidence indicating that people with stable angina who received ranolazine showed uncertain effect on the risk of cardiovascular death (for ranolazine given as monotherapy), all-cause death and non-fatal AMI, and the frequency of angina episodes (for ranolazine given as monotherapy) compared to those given placebo. Moderate quality evidence indicated that people with stable angina who received ranolazine showed uncertain effect on quality of life compared with people who received placebo. Moderate quality evidence also indicated that people with stable angina who received ranolazine as add-on therapy had fewer angina episodes but increased risk of presenting non-serious adverse events compared to those given placebo.

Manejo actual de la cardiopatía isquémica estable / Current management of stable ischemic heart disease

Introducción: Dependiendo de los estudios, se estima que la revascularización incompleta tras un cateterismo alcanza el 17-85% de los pacientes, y esto se asocia con un aumento de las hospitalizaciones, necesidad de nuevas revascularizaciones y muerte. Ranolazina es un fármaco antiisquémico empleado en el tratamiento de la angina estable. El objetivo de este estudio fue analizar si la adición de ranolazina al tratamiento estándar era capaz de mejorar el pronóstico de pacientes con una revascularización incompleta tras un intervencionismo coronario percutáneo. Métodos: Para ello se realizó un ensayo clínico multicéntrico, aleatorizado, de grupos paralelos, doble ciego, controlado con placebo y guiado por eventos. El estudio se desarrolló en 245 centros de 15 países en Europa, Israel, Rusia y EE. UU. Se incluyeron a pacientes ≥18 años con antecedentes de angina crónica y revascularización incompleta (≥una lesión con una estenosis ≥50% en una arteria coronaria ≥2mm de diámetro) realizada en los 14 días previos a la aleatorización. Los pacientes fueron aleatorizados por bloqueas a recibir ranolazina (en los primeros 7 días la dosis era 500mg 2 veces al día y, en caso de tolerarse, posteriormente se titulaba a 1.000mg bid) o placebo, añadidos al tratamiento estándar. La variable primaria del estudio fue el tiempo hasta la primera revascularización por isquemia u hospitalización por isquemia sin revascularización. El análisis se realizó por intención de tratar. Resultados: En total se incluyeron 2.651 pacientes (1.332 pacientes fueron asignados al grupo de ranolazina y 1.319 al grupo placebo). Tras una mediana de seguimiento de 643 días, la variable primaria ocurrió en el 26% de los pacientes tratados con ranolazina y en el 28% de los sujetos del grupo placebo (HR: 0,95; IC 95%: 0,82-1,10; p=0,48). Tampoco hubo diferencias significativas entre los grupos en las variables secundarias pre-especificadas de muerte súbita cardiaca, muerte cardiovascular o infarto de miocardio. El tratamiento con ranolazina fue bien tolerado, si bien las discontinuaciones por efectos secundarios fueron más frecuentes con ranolazina (14 frente al 11%; p=0,04). Los efectos adversos más relevantes incluyeron mareo, estreñimiento y náuseas. Conclusiones: Ranolazina no disminuyó el riesgo de la variable compuesta de revascularización por isquemia u hospitalización por isquemia sin revascularización en pacientes con antecedentes de angina crónica con revascularización incompleta tras un intervencionismo coronario percutáneo (AU)

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Is FFR-CT a "game changer" in the diagnostic management of stable coronary artery disease?

The introduction of fractional flow reserve computed tomography (FFR-CT) that is performed from static coronary CT angiography datasets may open new horizons in the diagnostic management of patients with suspected coronary artery disease. FFR-CT has a high sensitivity and moderate specificity in identifying ischemia in intermediate coronary stenoses. It has been demonstrated that this technology has the potential to significantly reduce the number of invasive coronary angiograms and the rate of normal coronary angiograms that are not followed by an intervention. Furthermore, initial data indicate that FFR-CT may predict the hemodynamic effect of stenting and even of bypass surgery. Thus, FFR-CT, with its capacity to serve as an effective gatekeeper before invasive angiography and the option to virtually predict the success of revascularization, constitutes a completely new concept in managing patients with stable angina pectoris. Before this exciting technology can enter clinical practice, however, some evident limitations need to be overcome and significantly more data concerning accuracy and influence on clinical and economic outcome parameters need to be generated.

Successful recanalisation of isolated chronic total occlusions improves outcomes in long-term observation: a case-control study.

BACKGROUND AND AIM: The long-term benefit of percutaneous recanalisation of chronic total occlusion (CTO) is still unclear. Given advances in interventional cardiology over the last two decades, we sought to investigate whether a successful percutaneous coronary intervention for CTO (PCI-CTO) improves outcomes in an age- and gender-matched single-centre cohort of stable angina patients. METHODS: Out of 401 consecutive patients enrolled to the CTO-Registry database, 276 patients were included in the final analysis. Patients with unsuccessful PCI-CTO (n = 138) were age- and gender-matched in a 1:1 ratio with patients who underwent a successful procedure. The primary end-points included hard end-points comprising death and nonfatal myocardial infarction (MI) and a composite safety outcome measure of death, nonfatal MI and ischaemia-driven revascularisation. The secondary end-point was improvement in angina status or complete resolution of angina symptoms. Patients were followed up for six months and at two years. RESULTS: Patients who underwent a successful recanalisation of CTO, compared to those who underwent an unsuccessful procedure, revealed similar rates of composite death and MI at six months (0.7% vs. 1.4%; hazard ratio [HR], 0.50; 95% confidence interval ratio [CI], 0.05-4.80; p = 0.56) and two years (1.4% vs. 5.8%; HR 0.24; 95% CI 0.07-0.85; p = 0.053). A significant difference in composite safety end-points between subsets, although not recorded after six months of observation (8.7% vs. 15.2%; HR 0.54; 95% CI 0.27-1.07; p = 0.095), was noted at two years follow-up (15.2% vs. 29.7%; HR 0.47; 95% CI 0.29-0.77; p = 0.004). A greater improvement in symptom burden or resolution of angina symptoms was documented after a successful PCI at both six months (68.1% vs. 23.2%, p < 0.001; 80.4% vs. 34.8%, p < 0.001, respectively) and two years (52.2% and 8.0%, p < 0.001; 68.1% vs. 22.5%, p < 0.001, respectively). CONCLUSIONS: Successful recanalisation of CTO improves outcomes in long-term observation.

[Diagnostics and therapy of ischemia in chronic stable angina pectoris. Role of echocardiography]. / Diagnostik und Therapie der chronischen Myokardischämie. Rolle der Echokardiographie.

Early detection of prognostically significant coronary artery disease (CAD) using ischemic tests, including noninvasive cardiac imaging, are fundamental approaches of optimized patient treatment guidelines to lower morbidity and mortality of these patients. Current international guidelines and the national standard of care guidelines from 2006 and 2011 as well as the third universal definition of myocardial infarction stress the increasing role of echocardiography as a favorable noninvasive imaging test. Echocardiography at rest, ergometric and pharmacologic stress echocardiography are established and readily available diagnostic tools with the potential to evaluate global and regional left ventricular function at rest and during exercise combined with information regarding regional perfusion. Especially new data on perfusion analysis allow further extension of the indications spectrum of reperfusion analysis and sensitivity increases in chest pain unit settings. The noninvasive detection of significant and prognostic stenosis burden in CAD without radiation is possible with high sensitivity and good specificity and encompasses functional cardiovascular parameters as well as extension of the ischemic area.The likelihood of future cardiac events can be assessed with high negative predictive accuracy, giving a high safety aspect in the treatment options of patients. The diagnostic potential of stress echocardiography is best in patients with intermediate and higher pretest probabilities. In patients under concurrent antiischemic medication identification of high risk patients seems feasible. Stress echocardiography has an excellent specificity and prognostic value for either indications for revascularization or survival prediction as well as survival benefits after revascularization in test positive patients.The detection of pathologic findings is not impaired by gender differences. New technical approaches include 2-D and 3-D speckle analysis of the myocardial wall and contrast-enhanced improvements in myocardial border delineation and perfusion. A new European multicenter study published in 2013 could demonstrate comparable to improved sensitivities in intermediate to severe coronary stenosis from 50% to 70% and in highly obstructive proximal stenoses compared to a reference electrocardiogram (ECG)-gated single photon emission computed tomography (SPECT).

In patients with chronic stable angina, secondary prevention appears better in the very old compared to younger patients: the Coronary Artery Disease in gENeral practiCE (CADENCE) Substudy.

BACKGROUND: With our aging communities and the increased prevalence of coronary heart disease (CAD) with age, the impact of this disease in the very old warrants further investigation. OBJECTIVE: To assess health outcomes and the attainment of guideline-based secondary prevention targets in the very old (>80 years, n=482) as compared to young (<65 years, n=582) and elderly (between 65 and 80 years, n=932) patients, all of whom had chronic stable angina. DESIGN: The coronary artery disease in general practice (CADENCE) study was a cluster-stratified cross-sectional survey. This study reports on health outcomes quantitated using the Seattle Angina Questionnaire and guideline targets achieved for blood pressure, smoking, lipids, diabetic control and body habitus. SETTINGS AND PARTICIPANTS: 2031 stable angina patients were recruited from 207 primary care practices. RESULTS: Despite similar angina frequency scores, the very old were more physically impaired by their angina than both the young and elderly [76±25 (Young) vs. 70±26 (Elderly) vs. 63±28 (Very old), p<0.05 for both comparisons]. However, the very old had better quality of life scores than young stable angina patients [72±24 vs. 65±25, p<0.05] and were similar to the elderly [72±24 vs. 72±23, p>0.05]. Also blood pressure, lipid, diabetic and body habitus targets were more often achieved in the very old and elderly patients compared to young stable angina patients. CONCLUSION: Despite similar symptomatic status and greater physical limitations, the very old reported a better quality of life and more often achieved treatment targets than young stable angina patients. Failure to improve secondary prevention measures in younger age groups may potentially contribute to increased morbidity in older age, and failure to achieve 'Healthy Ageing'.

Something is amiss in Denmark: a comparison of preventable hospitalisations and readmissions for chronic medical conditions in the Danish Healthcare system and Kaiser Permanente.

BACKGROUND: As many other European healthcare systems the Danish healthcare system (DHS) has targeted chronic condition care in its reform efforts. Benchmarking is a valuable tool to identify areas for improvement. Prior work indicates that chronic care coordination is poor in the DHS, especially in comparison with care in Kaiser Permanente (KP), an integrated delivery system based in the United States. We investigated population rates of hospitalisation and readmission rates for ambulatory care sensitive, chronic medical conditions in the two systems. METHODS: Using a historical cohort study design, age and gender adjusted population rates of hospitalisations for angina, heart failure, chronic obstructive pulmonary disease, and hypertension, plus rates of 30-day readmission and mortality were investigated for all individuals aged 65+ in the DHS and KP. RESULTS: DHS had substantially higher rates of hospitalisations, readmissions, and mean lengths of stay per hospitalisation, than KP had. For example, the adjusted angina hospitalisation rates in 2007 for the DHS and KP respectively were 1.01/100 persons (95%CI: 0.98-1.03) vs. 0.11/100 persons (95%CI: 0.10-0.13/100 persons); 21.6% vs. 9.9% readmission within 30 days (OR = 2.53; 95% CI: 1.84-3.47); and mean length of stay was 2.52 vs. 1.80 hospital days. Mortality up through 30 days post-discharge was not consistently different in the two systems. CONCLUSIONS: There are substantial differences between the DHS and KP in the rates of preventable hospitalisations and subsequent readmissions associated with chronic conditions, which suggest much opportunity for improvement within the Danish healthcare system. Reductions in hospitalisations also could improve patient welfare and free considerable resources for use towards preventing disease exacerbations. These conclusions may also apply for similar public systems such as the US Medicare system, the NHS and other systems striving to improve the integration of care for persons with chronic conditions.

Multiple marker approach to risk stratification in patients with stable coronary artery disease.

AIMS: multimarker approaches for risk prediction in coronary artery disease have remained inconsistent. We assessed multiple biomarkers representing distinct pathophysiological pathways in relation to cardiovascular events in stable angina. METHODS AND RESULTS: we investigated 12 biomarkers reflecting inflammation [C-reactive protein, growth-differentiation factor (GDF)-15, neopterin], lipid metabolism (apolipoproteins AI, B100), renal function (cystatin C, serum creatinine), and cardiovascular function and remodelling [copeptin, C-terminal-pro-endothelin-1, mid-regional-pro-adrenomedullin (MR-proADM), mid-regional-pro-atrial natriuretic peptide (MR-proANP), N-terminal-pro-B-type natriuretic peptide (Nt-proBNP)] in 1781 stable angina patients in relation to non-fatal myocardial infarction and cardiovascular death (n = 137) over 3.6 years. Using Cox proportional hazards models and C-indices, the strongest association with outcome for log-transformed biomarkers in multivariable-adjusted analyses was observed for Nt-proBNP [hazard ratio (HR) for one standard deviation increase 1.65, 95% confidence interval (CI) 1.28-2.13, C-index 0.686], GDF-15 (HR 1.59, 95% CI 1.25-2.02, C-index 0.681), MR-proANP (HR 1.46, 95% CI 1.14-1.87, C-index 0.673), cystatin C (HR 1.39, 95% CI 1.10-1.75, C-index 0.671), and MR-proADM (HR 1.63, 95% CI 1.21-2.20, C-index 0.668). Each of these top single markers and their combination (C-index 0.690) added predictive information beyond the baseline model consisting of the classical risk factors assessed by C-index and led to substantial reclassification (P-integrated discrimination improvement <0.05). CONCLUSION: comparative analysis of 12 biomarkers revealed Nt-proBNP, GDF-15, MR-proANP, cystatin C, and MR-proADM as the strongest predictors of cardiovascular outcome in stable angina. All five biomarkers taken separately offered incremental predictive ability over established risk factors. Combination of the single markers slightly improved model fit but did not enhance risk prediction from a clinical perspective.