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Efficacy and safety of oral Panax notoginseng saponins for unstable angina patients: A meta-analysis and systematic review.
Duan, L, Xiong, X, Hu, J, Liu, Y, Wang, J
Phytomedicine : international journal of phytotherapy and phytopharmacology. 2018;:23-33
Abstract
BACKGROUND Panax notoginseng saponins (PNS) is one of the most important active ingredients in Panax notoginseng, which plays an important role against cardiovascular diseases in Traditional Chinese Medicine (TCM). METHODS This review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement. We searched the following databases from their inception to February 2017: CENTRAL, MEDLINE, EMBASE Database, WHO ICTRP, CNKI, WANFANG, VIP and SinoMed. All the randomized controlled trials (RCTs) based on PNS in patients with unstable angina (UA) which meet the standard were included. RESULT Seventeen studies were included in this systemic review. The included studies indicated that PNS has promising therapeutic effects on reduction of the primary end point [RR 0.05 (95% CI -0.07, -0.02); P < 0.001], electrocardiography (ECG) [RR 0.32 (95% CI 0.23, 0.46); P < 0.001], the frequency and duration of angina attacks [MD -1.88 (95% CI -2.03, -1.72); P < 0.001], and dosage of nitroglycerin [MD -1.13 (95% CI -1.70, -0.56); P < 0.001] of UA patients. Adverse events were described 9 included RCTs. CONCLUSION Oral PNS could reduce the end point, and improve the ECG, the frequency and duration of angina pectoris, dosage of nitroglycerin and lipids in UA patients. And the results indicated oral PNS is safe up to now. However, we need more multi-centre, large-sample, high-quality RCTs to provide high-quality evidence.
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Impact of high-density lipoprotein 3 cholesterol subfraction on periprocedural myocardial injury in patients who underwent elective percutaneous coronary intervention.
Harada, K, Kikuchi, R, Suzuki, S, Tanaka, A, Aoki, T, Iwakawa, N, Kojima, H, Hirayama, K, Mitsuda, T, Sumi, T, et al
Lipids in health and disease. 2018;(1):21
Abstract
BACKGROUND Periprocedural myocardial injury (PMI) is a major complication of percutaneous coronary intervention (PCI) and is associated with atherosclerotic coronary plaque and worse clinical outcomes. High-density lipoprotein cholesterol (HDL-C) is a protective factor for cardiovascular disease. However, the role of HDL-C subfractions, such as HDL2 cholesterol (HDL2-C) or HDL3 cholesterol (HDL3-C), in cardiovascular disease remains unclear. The purpose of the study was to investigate the relationship between HDL2-C and HDL3-C subfractions and the incidence of PMI in patients who underwent elective PCI. METHODS We enrolled 129 patients who underwent elective PCI for stable angina pectoris. PMI was defined as an increase in high-sensitivity troponin T levels > 5 times the upper normal limit (> 0.070 ng/mL) at 24 h after PCI. Serum HDL-C subfractions (HDL2-C and HDL3-C) were assessed using ultracentrifugation in patients with and those without PMI. RESULTS HDL3-C levels were significantly lower in patients with PMI than in those without (15.1 ± 3.0 mg/dL vs. 16.4 ± 2.9 mg/dL, p = 0.016) and had an independent and inverse association with PMI (odds ratio, 0.86; 95% confidence interval, 0.74-0.99; p = 0.038). When divided by the cut-off value of HDL3-C for PMI (14.3 mg/dL), the incidence of PMI was significantly higher in low HDL3-C patients than in high HDL3-C patients (51.2% vs. 30.2%, p = 0.020). CONCLUSIONS HDL3-C was an independent inverse predictor of PMI in patients who underwent elective PCI.
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WITHDRAWN: Trimetazidine for stable angina.
Ciapponi, A, Pizarro, R, Harrison, J
The Cochrane database of systematic reviews. 2017;(3):CD003614
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Abstract
BACKGROUND Patients with stable angina not controlled by monotherapy with nitrates, beta blockers, or calcium channel blockers are often treated with combinations of these drugs. There may be adverse effects from, or contraindications to, the use of combinations. In low risk groups, medical treatment appears to be as good an option as percutaneous transluminal coronary angioplasty in terms of averting myocardial infarction, death, or subsequent revascularization. Revascularization procedures are too costly or inaccessible for many patients in developing countries therefore effective and safe medical treatment is needed. Trimetazidine is a less well known anti-anginal drug that controls myocardial ischaemia through intracellular metabolic changes. Trimetazidine has been reported, in some studies, to be better tolerated than combined anti-anginal therapy; however it is not considered in published guidelines. OBJECTIVES To determine the efficacy and tolerability of trimetazidine in patients with stable angina. SEARCH METHODS We searched The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, LILACS and SCISEARCH, without language restriction, from inception to October 2003. Experts in the field were contacted to locate unpublished studies. SELECTION CRITERIA Randomised studies comparing trimetazidine with placebo, or other anti-angina drug in adults with stable angina. DATA COLLECTION AND ANALYSIS Two reviewers independently applied the inclusion criteria, assessed trial quality and extracted data. MAIN RESULTS Twenty-three studies (1378 patients) met the inclusion criteria. There was a paucity of information about mortality, cardiovascular events and quality of life. Trimetazidine, compared with placebo, reduced the number of weekly angina attacks ( mean difference -1.44, 95% CI -2.10 to -0.79; P < 0.0001), reduced weekly nitroglycerin tablet consumption (95% CI -1.47 to -2.20, -0.73; P < 0.0001) and improved exercise time to 1 mm segment depression (P = 0.0002). Four small trials (263 patients) compared trimetazidine against other anti-anginal agents. One favoured trimetazidine over nitrates. Three tended to favour alternative regimens but with confidence intervals consistent with both major increases and decreases in frequency of angina episodes. In this subgroup, adverse events were considered in 5 trials (448 patients) and totals of 2 versus 12 drop outs due to adverse events were observed in the trimetazidine and alternative regimens respectively, but this was mostly driven by a single trial. AUTHORS' CONCLUSIONS Trimetazidine is effective in the treatment of stable angina compared with placebo, alone or combined with conventional anti-anginal agents. Trimetazidine may result in fewer dropouts due to adverse events. Large, long term trials comparing trimetazidine with other anti-anginal drugs assessing clinically relevant important outcomes are required to establish its role in clinical management.
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Feasibility of Extracorporeal Shock Wave Myocardial Revascularization Therapy for Post-Acute Myocardial Infarction Patients and Refractory Angina Pectoris Patients.
Myojo, M, Ando, J, Uehara, M, Daimon, M, Watanabe, M, Komuro, I
International heart journal. 2017;(2):185-190
Abstract
Extracorporeal shockwave myocardial revascularization (ESMR) is one of the new treatment options for refractory angina pectoris (RAP), and some studies have indicated its effectiveness. A single-arm prospective trial to assess the feasibility of ESMR using Cardiospec for patients with post-acute myocardial infarction (AMI) and RAP was designed and performed. The patients were treated with 9 sessions of ESMR to the ischemic areas for 9 weeks. The feasibility measures included echocardiography; cardiac magnetic resonance imaging; troponin T, creatine kinase-MB (CK-MB), and brain natriuretic peptide testing; and a Seattle Angina Questionnaire (SAQ) survey. Three post-AMI patients and 3 RAP patients were enrolled. The post-AMI patients had already undergone revascularization with percutaneous coronary intervention (PCI) in the acute phase. In two patients, adverse events requiring admission occurred: one a lumbar disc hernia in a post-AMI patient and the other congestive heart failure resulting in death in an RAP patient. No apparent elevations in CK-MB and troponin T levels during the trial were observed. Echocardiography revealed no remarkable changes of ejection fraction; however, septal E/E' tended to decrease after treatments (11.6 ± 4.8 versus 9.2 ± 2.8, P = 0.08). Concerning the available SAQ scores for two RAP patients, one patient reported improvements in angina frequency and treatment satisfaction and the other reported improvements in physical limitations and angina stability. In this feasibility study, ESMR seems to be a safe treatment for both post-AMI patients and RAP patients. The efficacy of ESMR for post-AMI patients remains to be evaluated with additional studies.
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A Chinese patent medicine Salvia miltiorrhiza depside salts for infusion combined with conventional treatment for patients with angina pectoris: A systematic review and meta-analysis of randomized controlled trials.
Zhang, Y, Xie, Y, Liao, X, Jia, Q, Chai, Y
Phytomedicine : international journal of phytotherapy and phytopharmacology. 2017;:100-117
Abstract
BACKGROUND Currently, many trials have been conducted to investigate the beneficial and harmful effects of Salvia miltiorrhiza depside salts for infusion for treating patients with angina pectoris. It is important to systematically and criticallyevaluate the existing literature into providing a pooled effect to examine outcomes of angina pectoris with Salvia miltiorrhiza depside salts for infusion. PURPOSE A systematic review and meta-analysis were performed to determine the clinical curative effect and safety of Salvia miltiorrhiza depside salts for infusion for angina pectoris and provide clear evidence to inform clinical practice. METHOD The Cochrane Library, MEDLINE, EMBASE, and other four electronic Chinese databases were searched to identify relevant randomized controlled trials. Methodological quality and reporting quality of eligible studies was evaluated by using the Cochrane risk-of-bias tool and CONSORT for traditional Chinese medicine respectively. Meta-analysis was performed by RevMan 5.3 software. RESULT Fifty-six randomized controlled trials involving 5503 patients were included. Most of the trials were classified as having an unclear risk of bias because of poor reported methodology. The main outcomes are improvements in angina symptoms, ECG improvement and reduction of nitroglycerin use. CHD mortality or rate of CHD events was not reported in any trial. Meta-analysis showed that Salvia miltiorrhiza depside salts for infusion combined with conventional treatment was better than conventional treatment alone in improving angina symptoms (RR= 1.28, 95% CI 1.24 to 1.31, p < 0.00001), the frequency of angina attack (time/week)(WMD=-1.47, 95% CI -2.16 to -0.78), reducing clinical symptom scores (WMD=-0.55, 95% CI -0.57 to -0.53, p < 0.000011), increasing physical limitation scores (WMD= 7.68, 95% CI 1.48 to 13.88, p = 0.02), improving ECG (RR= 1.32,95% CI 1.27 to 1.38, p < 0.00001) and reducing dosage of nitroglycerin (RR= 1.50, 95% CI: 1.26 to 1.77, p < 0.00001). In addition, Egger's regression tests was found there was publication bias (Kendall' tau= 0.36, p < 0.01). CONCLUSION The current systematic review indicates relevant evidence for Salvia miltiorrhiza depside salts for infusion combined with conventional treatments treating patient with angina pectoris. However, the results should be interpreted with caution due to the low methodological quality, the risk of publication bias, lack of important clinically relevant outcomes and inadequate reporting on adverse events of the included trials. International methodological and reporting standards could help researchers conduct well designed trials and generate better evidence for Salvia miltiorrhiza depside salts for infusion.
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Real-world Evidence for the Antianginal Efficacy of Trimetazidine from the Russian Observational CHOICE-2 Study.
Glezer, M, ,
Advances in therapy. 2017;(4):915-924
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INTRODUCTION The guidelines recommend a beta-blocker or calcium channel blocker as the first-line medication for angina, supplemented by other agents for additional symptoms. One such agent is trimetazidine (TMZ), which has been shown to reduce the frequency of anginal episodes and improve exercise performance without affecting haemodynamic parameters. However, extensive real-world evidence for its efficacy in combination with first-line therapies has been lacking. METHODS The aim of this large-scale, Russian, multicentre, 6-month, open-label, prospective observational study was to assess the effect of adding TMZ modified release 35 mg bid to background antianginal therapy in the real-world clinical setting. RESULTS The study included 896 patients: 54% women, aged 29-90 years (42.6% >65 years), 63% with class II angina, and receiving beta-blockers alone or in combination (93%). Add-on TMZ reduced angina frequency and short-acting nitrate use within 2 weeks (both p < 0.0001) regardless of background therapy and maintained this effect over 6 months. It increased the proportion of patients with class I angina sixfold while decreasing that of class 3 angina almost fourfold. It also improved walking distance and well-being at 6 months (both p < 0.0001). Treatment was well tolerated. CONCLUSION Add-on TMZ is a safe and rapidly effective treatment for reducing angina attacks and nitrate use in the real-world clinical setting. It also increases exercise capacity and well-being. These effects are observed within 2 weeks and persist for at least 6 months.
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Prognostic Value of Coronary Artery Calcium in the PROMISE Study (Prospective Multicenter Imaging Study for Evaluation of Chest Pain).
Budoff, MJ, Mayrhofer, T, Ferencik, M, Bittner, D, Lee, KL, Lu, MT, Coles, A, Jang, J, Krishnam, M, Douglas, PS, et al
Circulation. 2017;(21):1993-2005
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BACKGROUND Coronary artery calcium (CAC) is an established predictor of future major adverse atherosclerotic cardiovascular events in asymptomatic individuals. However, limited data exist as to how CAC compares with functional testing (FT) in estimating prognosis in symptomatic patients. METHODS In the PROMISE trial (Prospective Multicenter Imaging Study for Evaluation of Chest Pain), patients with stable chest pain (or dyspnea) and intermediate pretest probability for obstructive coronary artery disease were randomized to FT (exercise electrocardiography, nuclear stress, or stress echocardiography) or anatomic testing. We evaluated those who underwent CAC testing as part of the anatomic evaluation (n=4209) and compared that with results of FT (n=4602). We stratified CAC and FT results as normal or mildly, moderately, or severely abnormal (for CAC: 0, 1-99 Agatston score [AS], 100-400 AS, and >400 AS, respectively; for FT: normal, mild=late positive treadmill, moderate=early positive treadmill or single-vessel ischemia, and severe=large ischemic region abnormality). The primary end point was all-cause death, myocardial infarction, or unstable angina hospitalization over a median follow-up of 26.1 months. Cox regression models were used to calculate hazard ratios (HRs) and C statistics to determine predictive and discriminatory values. RESULTS Overall, the distribution of normal or mildly, moderately, or severely abnormal test results was significantly different between FT and CAC (FT: normal, n=3588 [78.0%]; mild, n=432 [9.4%]; moderate, n=217 [4.7%]; severe, n=365 [7.9%]; CAC: normal, n=1457 [34.6%]; mild, n=1340 [31.8%]; moderate, n=772 [18.3%]; severe, n=640 [15.2%]; P<0.0001). Moderate and severe abnormalities in both arms robustly predicted events (moderate: CAC: HR, 3.14; 95% confidence interval, 1.81-5.44; and FT: HR, 2.65; 95% confidence interval, 1.46-4.83; severe: CAC: HR, 3.56; 95% confidence interval, 1.99-6.36; and FT: HR, 3.88; 95% confidence interval, 2.58-5.85). In the CAC arm, the majority of events (n=112 of 133, 84%) occurred in patients with any positive CAC test (score >0), whereas fewer than half of events occurred in patients with mildly, moderately, or severely abnormal FT (n=57 of 132, 43%; P<0.001). In contrast, any abnormality on FT was significantly more specific for predicting events (78.6% for FT versus 35.2% for CAC; P<0.001). Overall discriminatory ability in predicting the primary end point of mortality, nonfatal myocardial infarction, and unstable angina hospitalization was similar and fair for both CAC and FT (C statistic, 0.67 versus 0.64). Coronary computed tomographic angiography provided significantly better prognostic information compared with FT and CAC testing (C index, 0.72). CONCLUSIONS Among stable outpatients presenting with suspected coronary artery disease, most patients experiencing clinical events have measurable CAC at baseline, and fewer than half have any abnormalities on FT. However, an abnormal FT was more specific for cardiovascular events, leading to overall similarly modest discriminatory abilities of both tests. CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrials.gov. Unique identifier: NCT01174550.
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Traditional and Alternative Therapies for Refractory Angina.
Kocyigit, D, Gurses, KM, Yalcin, MU, Tokgozoglu, L
Current pharmaceutical design. 2017;(7):1098-1111
Abstract
Refractory angina (RFA) is an unfavourable condition that is characterized with persistent angina due to reversible myocardial ischemia in patients with coronary artery disease that remains uncontrollable despite an optimal combination of pharmacological agents and revascularization. Despite significant advances in revascularization techniques and agents used in pharmacological therapy, there is still a significant population suffering from RFA and the global prevalence is even increasing. Anti- anginal treatment and secondary risk-factor modification are the traditional approaches for this group of patients. Furthermore, now there is still a large number of alternative treatment options. In order to review traditional and alternative treatment strategies in patients with RFA, we searched Pubmed for articles in English using the search terms "pharmacological therapy, refractory angina", "alternative therapy, refractory angina" between inception to June 2016. We also went through separately for each alternative treatment modality on Pubmed. To identify further articles, we handsearched related citations in review articles and commentaries. We also included data from the European Society of Cardiology (2013), and the Canadian Society of Cardiology/ Canadian Pain Society (2012) guidelines. Data show that besides traditional pharmacological agents, such as nitrates, beta- blockers or calcium channel blockers, novel antiischemic drugs and if symptoms persist, several non- invasive and/ or invasive alternative strategies may be considered. Impact of some pharmacological agents, such as rho- kinase inhibitors, and novel alternative treatment modalities, such as coronary sinus reducers, stem cell therapy, gene and protein therapy, on outcomes are still under investigation.
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Ranolazine in patients with incomplete revascularisation after percutaneous coronary intervention (RIVER-PCI): a multicentre, randomised, double-blind, placebo-controlled trial.
Weisz, G, Généreux, P, Iñiguez, A, Zurakowski, A, Shechter, M, Alexander, KP, Dressler, O, Osmukhina, A, James, S, Ohman, EM, et al
Lancet (London, England). 2016;(10014):136-45
Abstract
BACKGROUND Incomplete revascularisation is common after percutaneous coronary intervention and is associated with increased mortality and adverse cardiovascular events. We aimed to assess whether adjunctive anti-ischaemic pharmacotherapy with ranolazine would improve the prognosis of patients with incomplete revascularisation after percutaneous coronary intervention. METHODS We performed this multicentre, randomised, parallel-group, double-blind, placebo-controlled, event-driven trial at 245 centres in 15 countries in Europe, Israel, Russia, and the USA. Patients (aged ≥18 years) with a history of chronic angina with incomplete revascularisation after percutaneous coronary intervention (defined as one or more lesions with ≥50% diameter stenosis in a coronary artery ≥2 mm diameter) were randomly assigned (1:1), via an interactive web-based block randomisation system (block sizes of ten), to receive either twice-daily oral ranolazine 1000 mg or matching placebo. Randomisation was stratified by diabetes history (presence vs absence) and acute coronary syndrome presentation (acute coronary syndrome vs non-acute coronary syndrome). Study investigators, including all research teams, and patients were masked to treatment allocation. The primary endpoint was time to first occurrence of ischaemia-driven revascularisation or ischaemia-driven hospitalisation without revascularisation. Analysis was by intention to treat. This study is registered at ClinicalTrials.gov, number NCT01442038. FINDINGS Between Nov 3, 2011, and May 27, 2013, we randomly assigned 2651 patients to receive ranolazine (n=1332) or placebo (n=1319); 2604 (98%) patients comprised the full analysis set. After a median follow-up of 643 days (IQR 575-758), the composite primary endpoint occurred in 345 (26%) patients assigned to ranolazine and 364 (28%) patients assigned to placebo (hazard ratio 0·95, 95% CI 0·82-1·10; p=0·48). Incidence of ischaemia-driven revascularisation and ischaemia-driven hospitalisation did not differ significantly between groups. 189 (14%) patients in the ranolazine group and 137 (11%) patients in the placebo group discontinued study drug because of an adverse event (p=0·04). INTERPRETATION Ranolazine did not reduce the composite rate of ischaemia-driven revascularisation or hospitalisation without revascularisation in patients with a history of chronic angina who had incomplete revascularisation after percutaneous coronary intervention. Further studies are warranted to establish whether other treatment could be effective in improving the prognosis of high-risk patients in this population. FUNDING Gilead Sciences, Menarini.
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Coronary Artery Calcium as an Independent Surrogate Marker in the Risk Assessment of Patients With Atrial Fibrillation and an Intermediate Pretest Likelihood for Coronary Artery Disease Admitted to a German Chest Pain Unit.
Breuckmann, F, Olligs, J, Hinrichs, L, Koopmann, M, Lichtenberg, M, Böse, D, Fischer, D, Eckardt, L, Waltenberger, J, Garvey, JL
Clinical cardiology. 2016;(3):157-64
Abstract
BACKGROUND About 10% of patients admitted to a chest pain unit (CPU) exhibit atrial fibrillation (AF). HYPOTHESIS To determine whether calcium scores (CS) are superior over common risk scores for coronary artery disease (CAD) in patients presenting with atypical chest pain, newly diagnosed AF, and intermediate pretest probability for CAD within the CPU. METHODS In 73 subjects, CS was related to the following risk scores: Global Registry of Acute Coronary Events (GRACE) score, including a new model of a frequency-normalized approach; Thrombolysis In Myocardial Infarction score; European Society of Cardiology Systematic Coronary Risk Evaluation (SCORE); Framingham risk score; and Prospective Cardiovascular Münster Study score. Revascularization rates during index stay were assessed. RESULTS Median CS was 77 (interquartile range, 1-270), with higher values in men and the left anterior descending artery. Only the modified GRACE (ρ = 0.27; P = 0.02) and the SCORE (ρ = 0.39; P < 0.005) were significantly correlated with CS, whereas the GRACE (τ = 0.21; P = 0.04) and modified GRACE (τ = 0.23; P = 0.02) scores were significantly correlated with percentile groups. Only the CS significantly discriminated between those with and without stenosis (P < 0.01). CONCLUSIONS Apart from modified GRACE score, overall correlations between risk scores and calcium burden, as well as revascularization rates during index stay, were low. By contrast, the determination of CS may be used as an additional surrogate marker in risk stratification in AF patients with intermediate pretest likelihood for CAD admitted to a CPU.