Treatment Of Chronic Stable Angina Research Articles

Economic evaluation of Danhong injection for the treatment of chronic stable angina in China: A cost-effectiveness analysis

Abstract Objective Danhong injection (DHI) is commonly used in China to treat chronic stable angina (CSA), demonstrating significant clinical efficacy and safety. The present study aimed to estimate the cost-effectiveness of DHI combined with standard treatment (ST) compared with ST alone in patients with CSA. Methods A Markov model with a 3-month cycle and a 1-year time horizon was used to assess the cost-effectiveness of DHI + ST for CSA. Health outcomes were measured as quality-adjusted life years (QALYs), and societal perspective costs were collected in China. Cost-effectiveness was evaluated using the incremental cost-effectiveness ratio (ICER). Sensitivity analysis was performed to test the robustness of results to parameter uncertainty. Results Analysis demonstrated DHI + ST provided 0.8190 QALYs at an average cost of $3644.24, while ST yielded 0.7884 QALYs costing $2739.54 over 1 year. The incremental analysis indicated DHI + ST dominance, with an ICER of $29,588.91 per QALY gained compared with ST. One-way sensitivity analysis confirmed the robustness of base case findings, and probabilistic sensitivity analysis suggested a 61.66% probability of DHI + ST being cost-effective over ST at a $37,663.26 per QALY threshold. Conclusion From a societal perspective in China, DHI + ST appears cost-effective for the treatment of CSA compared with ST alone. These findings support recommending DHI as a clinically valuable and cost-effective option in CSA treatment guidelines.

Assessing the holistic value of Danhong injection for chronic stable angina: a multi-criteria decision analysis in China

IntroductionThis study aimed to assess the holistic value of Danhong injection (DHI) for treating chronic stable angina (CSA) and to identify the therapeutic characteristics of DHI. MethodsThe holistic value of DHI was assessed using a well-established evaluation index system including 34 criteria based on the Multi-criteria decision analysis (MCDA) model. Each criterion was rated by seven experts based on an evidence matrix comprising a literature review on DHI for treating CSA. The overall value of DHI for the treatment of CSA was evaluated by aggregating these performance scores and predetermined weights. Additionally, the contributions of each domain and criterion to the overall value estimate were calculated. Uncertainty was explored using an online retest and intra-rater correlation coefficient (ICC). ResultsWe found that the comprehensive value estimate of DHI for treating CSA was 80.18 points. The domain of “safety and risk management” was the strongest contributor to the final estimated value (30.37), followed by “effectiveness” (23.75). The criteria “size of population affected by disease” (3.79), “risk control of toxic medicinal materials” (4.38), “comparative non-medical costs” (1.14), “clarity of the mechanism of drug action” (0.6), “sustainability of medicinal materials resources” (1.91) and “patient compliance” (4.59) were found to be the most significant contributors to the overall value estimate across the 6 evaluation domains. The initial scores for DHI over the two rounds showed good consistency across panelists (ICC=0.886 [0.858–0.909]). ConclusionCompared with standard treatment alone, DHI was perceived as being at a “good level” intervention.

High-throughput proteomic analysis unveils metabolic and mitochondrial signaling rewiring by chronic ivabradine treatment in duchenne muscular dystrophy

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Austrian Science Fund (FWF) Objective Ivabradine (IVA) is indicated in symptomatic treatment of chronic stable angina, heart failure, and also in those who are unable to tolerate or have contraindications to the use of beta-blockers. It has been showed IVA may have cardiovascular benefits in Duchenne muscular dystrophy (DMD) patients. This study was aimed to investigate the sustained impact of chronic ivabradine (IVA) administration on cardiac function and potential underlying mechanism using high throutput proteomic analysis. Methods DMDmdx male and Sprague–Dawley wt (Sprague–Dawley) male rats were randomly allocated to vehicle (n = 6) or IVA (n=6; 10 mg/kg/day via drinking water for four months). Transthoracic echocardiography and unbiased proteomic analysis were performed to assess cardiac function and left ventricular (LV) tissue, respectively. Protein-protein interactions were graphically represented, and cluster analysis with subsequent enrichment analyses was conducted. Results Chronic IVA treatment significantly enhanced the LV ejection fraction (p<0.05 compared to vehicle-treated DMDmdx rats). Proteomic data identified possible transcription factors (SPI1, IRF1, PPARA), consistent with previous studies. The reduction in copper metabolic changes associated with DMD can be attributed to the upregulation of Atox1 following IVA treatment. Mitochondrial dysfunction was effectively mitigated by IVA, as indicated by the different abundance of mitochondrial proteins. In addition, intercellular adhesion molecule 1 showed a reduction in the number of animals treated with ivabradine, indicating a further positive effect of the treatment. Conclusion In summary, this study demonstrated the beneficial effects of IVA in DMDmdx rat hearts. Cluster analysis of proteomic data revealed notable changes in cardiac metabolism, inflammation, and mitochondrial function. Ivabradine has emerged as a potential therapeutic approach to address these shifts, while proteomic pathway analysis may uncover new drugable targets to alleviate cardiomyopathy progression in DMD.Interaction of IvabradinProtein-protein interaction network

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.

Ranolazine: a better understanding of its pathophysiology and patient profile to guide treatment of chronic stable angina.

Chronic stable angina pectoris, the most prevalent symptomatic manifestation of coronary artery disease, greatly impairs quality of life and is associated with an increased risk for adverse cardiovascular outcomes. Better understanding of the pathophysiologic mechanisms of myocardial ischemia permitted new therapeutic strategies to optimize the management of angina patients. Ideally, antianginal drug treatment should be tailored to individual patient's profile and chosen according to the pathophysiology, hemodynamic profile, adverse effects, potential drug interactions and comorbidities. In this respect, and because of its peculiar mechanism of action, ranolazine represents an alternative therapeutic approach in patients with chronic stable angina and may be considered the first choice in presenceof comorbiditiesthat difficult the use of traditional therapies.

Efficacy and safety of Naoxintong capsule for treating chronic stable angina: study protocol for a randomized controlled trial

BackgroundCardiovascular disease is the leading cause of mortality and morbidity worldwide, Chronic stable angina (CSA) is the main symptom of myocardial ischemia, causes increased risk of major cardiovascular events such as sudden cardiac death and myocardial infarction. Naoxintong (NXT) capsule is a classical traditional Chinese medication used to treat CSA, however, few evidence to support the wide utility of NXT capsule for the treatment of CSA. We design this study to evaluate the efficacy and safety of NXT capsule versus placebo in patients with CSA.Methods/designThis is a multicenter, randomized, double-blind, placebo-controlled clinical trial. A total of 260 eligible participants will be enrolled. The participants will be randomized assigned in an equal ratio to groups receiving either NXT or placebo for 12 weeks. After a 2-week run-in period, they will receive either NXT or placebo (3 pills, 3 times daily) for 12 weeks. The primary outcome is therapeutic efficacy. Secondary outcome measures include the quantitative score of TCM syndromes, severity grading of angina pectoris, the number of angina pectoris per week, nitroglycerin dosage, score of Seattle angina scale, serum homocysteine, and incidence of cardiovascular events. Safety outcomes and adverse events will be monitored throughout the trial.DiscussionWe designed this study in accordance with principles and regulations issued by the China Food and Drug Administration (CFDA). The results will provide clinical evidence of the efficacy and safety of NXT Capsule in the treatment of CSA.Trial registrationChinese Clinical Trial Registry ChiCTR2100044563. Registered on 24 March 2020.

Research on acupuncture treatment of chronic stable angina by Chinese scholars

Research on acupuncture treatment of chronic stable angina by Chinese scholars

Efficacy and safety of Xinnaoning capsule in treating chronic stable angina (qi stagnation and blood stasis syndrome): Study protocol for a multicenter, randomized, double-blind, placebo-controlled trial.

Chronic stable angina (CSA) is a cardiovascular disease with high prevalence. At present, drug treatment is still the main measure of stable angina pectoris. Traditional Chinese medicine has a long history in the treatment of CSA. Qi stagnation and Blood stasis syndrome is a common syndrome of CSA. Xinnaoning (XNN) capsule is considered as an effective adjuvant treatment for CSA with the efficacy of promoting qi and blood circulation but lack of high-quality clinical evidence. The purpose of this study is to evaluate the efficacy and safety of XNN capsule compared with placebo by clinical trial. This multicenter, randomized, double-blind, placebo-controlled trial will be conducted with a total of 240 participants diagnosed with chronic stable angina (qi stagnation and blood stasis syndrome). The participants will be randomized (1:1) into groups receiving either XNN or placebo for 12 weeks. After a 2-week run-in period, they will receive either XNN or placebo (3 pills, 3 times daily) for 12 weeks on the basis of conventional therapy. The primary outcomes include changes in the integral scores of angina symptoms. The secondary outcome measures include changes in the total score of traditional Chinese medicine syndrome, severity grading of angina pectoris, the number of angina pectoris per week, nitroglycerin dosage, score of seattle angina scale, serum homocysteine, incidence of cardiovascular events. Safety outcomes will also be assessed. Adverse events will be monitored throughout the trial. This study will investigate whether XNN capsule can alleviate clinical symptoms, and improve quality of life of patients with chronic stable angina (qi stagnation and blood stasis syndrome). The results of this study will provide clinical evidence for the application of XNN capsule in the treatment of chronic stable angina. ClinicalTrials.gov: NCT03914131.

Guanxinjing capsule in the treatment of chronic stable angina: study protocol for a randomized controlled trial

BackgroundStable angina is a common cardiovascular disease with high mortality and a poor prognosis. Although there are various interventions against stable angina, none are able to significantly reduce the mortality rate. Guanxinjing capsule (GXJ) is made from the classical Chinese prescription Xuefuzhuyutang (血府逐瘀汤). Both basic research and clinical studies have shown that GXJ can relieve the symptoms of angina, but currently, the effects of GXJ lack high-quality clinical evidence. The aim of this study was to evaluate the clinical effectiveness and safety of GXJ compared with placebo.Methods/designThis multicentre, blinded, randomized trial will be conducted with a total of 120 participants diagnosed with chronic stable angina (Qi deficiency and blood stasis syndrome). Using a central randomization system, participants will be randomized (1:1) into groups receiving either GXJ or placebo for 8 weeks. After a 2-week run-in period, eligible patients will receive either GXJ or placebo (4 pills, three times daily) for 8 weeks in addition to conventional treatment. The primary outcomes include changes in the total exercise time on exercise tolerance tests and changes in the integral scores of angina symptoms. The secondary outcome measures include changes in the maximal estimated workload, changes in time to a 1 mm ST-segment depression or raise, changes in the time to onset of angina during exercise tolerance testing, changes in the total score of traditional Chinese medicine syndrome, and changes in the total score of the Generalized Anxiety Disorder 7-item assessment between baseline and week 8. Other outcome measures will also be assessed. All exercise tolerance tests use a standard Bruce multistage exercise test protocol. Adverse events will be monitored throughout the trial.DiscussionThis study will investigate whether GXJ can alleviate clinical symptoms, increase the angina-free walking time, and improve quality of life in patients with chronic stable angina (Qi deficiency and blood stasis syndrome). The results of this study will provide clinical evidence for the application of GXJ to the treatment of stable angina.Trial registrationChinese Clinical Trial Registry, ChiCTR1800014258. Registered on 2 January 2018.

The Pharmacological and Clinical Evidences of a Multi-herbal Drug Product - Dantonic (T89) Indicated for the Prevention and Treatment of Chronic Stable Angina - for FDA Registration

The Pharmacological and Clinical Evidences of a Multi-herbal Drug Product - Dantonic (T89) Indicated for the Prevention and Treatment of Chronic Stable Angina - for FDA Registration

Ranolazine for the treatment of chronic stable angina: a cost-effectiveness analysis from the UK perspective

ObjectivesTo estimate the cost-effectiveness of ranolazine when added to standard-of-care (SoC) antianginals compared with SoC alone in patients with stable coronary disease experiencing ≥3 attacks/week.SettingAn economic model utilising a UK...

Danhong injection in the treatment of chronic stable angina: study protocol for a randomized controlled trial.

BackgroundChronic stable angina is a leading cause of death worldwide. Danhong injection, a complementary alternative medicine for chronic stable angina, has been demonstrated to be effective in numerous studies and is widely prescribed to patients. However, the methodological quality of most prior studies was found to be, in general, low. Therefore, we designed this randomized controlled trial to evaluate the efficacy and safety of using Danhong injection to treat chronic stable angina.Methods/designThis is a randomized multicentre, double-blind, placebo-controlled, adaptive clinical trial. A total of 870 patients meeting the eligibility criteria will be randomly assigned into either the Danhong injection or the placebo group in a 2:1 ratio. Participants will then undergo a 2-week treatment regimen and a 76-day follow-up period. Because this is an adaptive trial, two interim analyses are prospectively planned. These will be performed after one-third and two-thirds of the patients, respectively, have completed the trial. Based on the results of these interim analyses, a data monitoring committee will determine how to modify aspects of the study without undermining the validity and integrity of the trial. The primary outcome measure is the proportion of patients who show a clinically significant change, which is defined as at least a 20-point improvement in angina frequency score on the Seattle Angina Questionnaire, which will be administered on day 30. Other secondary efficacy and safety outcomes will also be assessed.DiscussionThis trial will provide high-quality evidence regarding the use of Danhong injection to treat chronic stable angina.Trial registrationClinicalTrials.gov: NCT01681316.

The Effectiveness and Cost-Effectiveness of Spinal Cord Stimulation for Refractory Angina (RASCAL Study): A Pilot Randomized Controlled Trial.

BackgroundPatients with “refractory angina” (RA) unsuitable for coronary revascularization experience high levels of hospitalization and poor health‐related quality of life. Randomized trials have shown spinal cord stimulation (SCS) to be a promising treatment for chronic stable angina and RA; however, none has compared SCS with usual care (UC). The aim of this pilot study was to address the key uncertainties of conducting a definitive multicenter trial to assess the clinical and cost‐effectiveness of SCS in RA patients, i.e., recruitment and retention of patients, burden of outcome measures, our ability to standardize UC in a UK NHS setting.Methods RA patients deemed suitable were randomized in a 1:1 ratio to SCS plus UC (SCS group) or UC alone (UC group). We sought to assess: recruitment, uptake, and retention of patients; feasibility and acceptability of SCS treatment; the feasibility and acceptability of standardizing UC; and the feasibility and acceptability of the proposed trial outcome measures. Patient outcomes were assessed at baseline (prerandomization) and three and six months postrandomization.ResultsWe failed to meet our planned recruitment target (45 patients) and randomized 29 patients (15 SCS group, 14 UC group) over a 42‐month period across four sites. None of the study participants chose to withdraw following consent and randomization. With exception of two deaths, all completed evaluation at baseline and follow‐up. Although the study was not formally powered to compare outcomes between groups, we saw a trend toward larger improvements in both primary and secondary outcomes in the SCS group.ConclusionsWhile patient recruitment was found to be challenging, levels of participant retention, outcome completion, and acceptability of SCS therapy were high. A number of lessons are presented in order to take forward a future definitive pragmatic randomized trial.

Old and New Drugs for Treatment of Stable Angina: New Anti-Anginal Drugs and Coronary Revascularization.

Since the first human catheterization performed by Forssman in 1929 angioplasty equipment and medical therapies have undergone considerable evolution and technical improvement allowing interventionalists to perform more complex procedures and solving most of the percutaneous limitations. While percutaneous coronary intervention (PCI) has dramatically changed the outcome in the Acute Coronary Syndrome (ACS) setting, its role in the treatment of chronic stable angina is still debated. Stable coronary artery disease (SCAD) is a major public health issue and its prevalence is still increasing in the industrialized world. The correct treatment sees a multi-strategy approach aimed to a relief of symptoms, prevention of future cardiac events and survival improvement. In so forth, treatment strategies include optimal medical therapy (OMT) alone or combined with percutaneous or surgical coronary revascularization. Despite this, angina remains poorly controlled in the vast majority of CAD patients. Traditional agents such Beta-blockers or Calcium channel blockers or short and long acting nitrates have been used as first-line anti-anginal therapy for several years. Nowadays newer and more effective drugs usually used on top of older medical treatment have become available.

A multicenter, randomized, double-blind clinical study on Wufuxinnaoqing Soft Capsule (五福心脑清胶囊) in treatment of chronic stable angina patients with blood stasis syndrome

To confirm the efficacy and safety of Wufuxinnaoqing Soft Capsule (, WSC) in the treatment of chronic stable angina (blood stasis syndrome). A multicenter, randomized, double-blind, placebo-controlled trial with superiority test was designed. A total of 240 patients with chronic stable angina (blood stasis syndrome) from multiple centers were randomly and equally assigned to the treatment group and the control group. Based on standard treatment of Western medicine, the treatment group was given WSC, while the control group was given WSC mimetic, both for 12 weeks. Observed indicators included the efficacy in angina, the efficacy in Chinese medicine syndrome, the withdrawal or reduce rate of nitroglycerin and routine safety indices. After 12-week treatment, the significant effective rate and total effective rate of the treatment group were significantly better than those of the control group (23.5% vs. 9.2%, 64.7% vs. 30.8%), respectively, with statistically significant difference (P<0.01). After 12-week treatment, the decreased points and the decreased rate of angina symptom score in the treatment group were better than in the control group (5.1±4.2 points vs. 2.8±3.5 points, 44.9%±37.2% vs. 25.4%±30.7%) respectively, with significant difference (P<0.01). After 12-week treatment, the significant effective rate and total effective rate of the treatment group were better than the control group (respectively, 30.3% vs. 15.0%, 67.2% vs. 45.0%,P<0.01). After 8- or 12-week treatment, the decreased points and the decreased rate of Chinese medicine syndrome score in the treatment group were better than the control group (P<0.05 orP<0.01). After 12-week treatment, nitroglycerin withdrawal rate and the withdrawal or reduce rate in treatment group were better than the control group (P<0.01). On safety evaluation, the incidence of adverse events (7.563% vs. 7.500%) and the incidence of cardiovascular events (0.840% vs. 0.000%) in the treatment group were similar with the control group, and the difference was not statistically significant (P>0.05). In treatment of chronic stable angina (blood stasis syndrome), WSC can reduce angina attacks and consumption of nitroglycerin, decrease angina severity degree, effectively relieve the blood stasis syndromes, such as chest pain, chest tightness, palpitations, dark purple tongue and other symptoms. Besides, adverse events and cardiovascular adverse events in the treatment group and the control group showed no difference. All shows that the drug is safe and effective. [This study was registered in Chinese Clinical Trial Registry (ChiCTR), with registration number: ChiCTR-TRC-14005158.].

In-Vitro, Ex-Vivo and In-Vivo Evaluation of Transdermal Delivery of Felodipine

Felodipine, an effective calcium channel blocker, widely used for the treatment of chronic stable angina and hypertension seems to be potential therapeutic transdermal system candidate, mainly due to its low oral bioavailability, short half life and high first-pass metabolism. Hence an attempt was made to develop transdermal therapeutic systems for felodipine using the polymer blend of eudragit RL100 (ERL) and hydroxypropyl methylcellulose (HPMC) by casting method and to study the effect of polymer composition, plasticizer and permeation enhancer on the physico-mechanical and in vitro drug release characteristics of the film. Polyethylene glycol 400 (PEG 400) and span 60 were used as plasticizer and permeation enhancer respectively. Incorporation of HPMC and PEG 400 improved the flexibility, folding endurance and handling properties and in vitro drug release of the films. The patches were also evaluated for ex vivo skin permeation using human cadaver skin. The presence of span 60 produced significant increase in the flux and permeability. The formulation with ERLHPMC ratio 2:3,4% w/w span 60 as permeation enhancer and 7.5% w/w PEG 400 as plasticizer showed the best results which exhibited the cumulative percentage of drug release of 84.96% and the cumulative amount of drug permeation across skin of 4861.4ng/cm 2 in 24 hrs. In vivo studies of this transdermal system in rabbits demonstrated a four fold enhancement of bioavailability of felodipine relative to oral administration. It may be concluded that the fabricated transdermal delivery system have the potential to provide controlled and extended drug release, better bioavailability and thus, they may improve the patient compliance.

Funny current in cardiac pacemaker cells and its specific inhibitor ivabradine

Out of all the electrical discharges occurring in the cardio myocytes, the funny current (If) or the pacemaker current (Ir) is rather unusual. The existence of such an electrical activity in the sinoatrial node was established in 1970’s. Because of their relevance to generation of pacemaker activity and modulation of spontaneous frequency, f-channels are natural targets of drugs aimed to pharmacologically control heart rate. Ivabradine is the most specific and selective If inhibitor and the only member of this family that is now marketed for pharmacological treatment of chronic stable angina in patients with normal sinus rhythm who have a contraindication or intolerance to beta-blockers. Recent studies have also indicated that funny channel inhibition can be used to reduce the incidence of coronary artery disease outcomes.

Identification of the Molecular Site of Ivabradine Binding to HCN4 Channels

Ivabradine is a specific heart rate-reducing agent approved as a treatment of chronic stable angina. Its mode of action involves a selective and specific block of HCN channels, the molecular components of sinoatrial "funny" (f)-channels. Different studies suggest that the binding site of ivabradine is located in the inner vestibule of HCN channels, but the molecular details of ivabradine binding are unknown. We thus sought to investigate by mutagenesis and in silico analysis which residues of the HCN4 channel, the HCN isoform expressed in the sinoatrial node, are involved in the binding of ivabradine. Using homology modeling, we verified the presence of an inner cavity below the channel pore and identified residues lining the cavity; these residues were replaced with alanine (or valine) either alone or in combination, and WT and mutant channels were expressed in HEK293 cells. Comparison of the block efficiency of mutant vs WT channels, measured by patch-clamp, revealed that residues Y506, F509 and I510 are involved in ivabradine binding. For each mutant channel, docking simulations correctly explain the reduced block efficiency in terms of proportionally reduced affinity for ivabradine binding. In summary our study shows that ivabradine occupies a cavity below the channel pore, and identifies specific residues facing this cavity that interact and stabilize the ivabradine molecule. This study provides an interpretation of known properties of f/HCN4 channel block by ivabradine such as the “open channel block”, the current-dependence of block and the property of "trapping" of drug molecules in the closed configuration.

Evaluating symptoms to improve quality of life in patients with chronic stable angina.

Chronic stable angina (CSA) is a significant problem in the United States that can negatively impact patient quality of life (QoL). An accurate assessment of the severity of a patient's angina, the impact on their functional status, and their risk of cardiovascular complications is key to successful treatment of CSA. Active communication between the patient and their healthcare provider is necessary to ensure that patients receive optimal therapy. Healthcare providers should be aware of atypical symptoms of CSA in their patients, as patients may continue to suffer from angina despite the availability of multiple therapies. Patient questionnaires and symptom checklists can help patients communicate proactively with their healthcare providers. This paper discusses the prevalence of CSA, its impact on QoL, and the tools that healthcare providers can use to assess the severity of their patients' angina and the impact on QoL.

Effects of Ranolazine on Vasomotor Responses of Rat Aortic Rings

Ranolazine is a piperazine derivative that was approved in 2006 for the treatment of chronic stable angina. Compared with first-line drugs currently used to treat angina, beneficial effects of ranolazine occur without changing hemodynamic parameters such as heart rate and blood pressure. In the present study the effects of ranolazine on vasomotor responses of rat aortic rings were examined. Pharmacological evaluation was performed by analyzing the vasomotor responses of ranolazine on aortic rings of adult male Wistar rats precontracted with phenylephrine (10(-5) M). In each experiment we used a pair of rings (with and without endothelium) from the same aorta and superfused in the same bath. Ranolazine (10(-6)-10(-4) M) induced a concentration-dependent relaxation of phenylephrine-precontracted rings. The relaxation was only partially dependent on the presence of the endothelium (56.78 ± 6.81% in rings with endothelium and 47.88 ± 4.70% in rings without endothelium). In rings with endothelium, L-NAME induced a shift to the right of the concentration-response curve to ranolazine. Blocking the cyclooxygenase pathway induced a leftward shift of the concentration relaxation curve to ranolazine in both types of rings and increased the ranolazine-induced relaxation in rings without endothelium. Ranolazine has a vasodilatory effect that is predominantly endothelium-independent. The synthesis/release of nitric oxide by the endothelium may, however, contribute to its relaxing action. These effects of ranolazine may contribute to its beneficial effects in patients with stable angina.