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CJC Open Jan 2021Coronary microvascular dysfunction (CMD) is a common cause of angina and exercise intolerance in patients without obstructive coronary artery disease. The efficacy of... (Review)
Review
BACKGROUND
Coronary microvascular dysfunction (CMD) is a common cause of angina and exercise intolerance in patients without obstructive coronary artery disease. The efficacy of ranolazine, a late sodium channel blocker, in patients with symptomatic obstructive coronary artery disease is well established. To evaluate the efficacy of ranolazine in CMD, we performed a systematic review and meta-analysis of randomized studies.
METHODS
MEDLINE, EMBASE, Cochrane CENTRAL, and conference abstracts were searched from January 1975 to March 2020. Randomized trials evaluating ranolazine in patients with CMD were screened. Two reviewers independently extracted data and assessed study quality. End points of interest included a change in angina measured by the Seattle Angina Questionnaire (SAQ), coronary flow reserve (CFR), and clinical outcomes. Data were combined using random-effects models.
RESULTS
Of 836 citations, 6 randomized studies (318 patients) were included. Median follow-up was 4 weeks. When pooling the 6 trials analyzing ranolazine, we found that patients treated with ranolazine had a higher SAQ value regarding physical functioning (mean difference, 6.42; 95% confidence interval [CI], 2.41; 10.42) quality of life (10.07; 95% CI, 3.4; 16.74), and angina stability (20.14; 95% CI, 10.12; 30.17), as well as improved CFR (0.27; 95% CI, 0.09; 0.45) compared with placebo/control therapy. A high heterogeneity was observed (range , 30%-84%).
CONCLUSIONS
In CMD, ranolazine may be associated with improvements in CFR and some of the SAQ domains, including angina stability, physical functioning, and quality of life. However, it does not seem to beneficially impact angina frequency and treatment satisfaction. It is also unknown if it improves prognosis of afflicted patients.
PubMed: 33458636
DOI: 10.1016/j.cjco.2020.09.005 -
European Cardiology Feb 2023This article evaluates the efficacy of using ranolazine to improve diastolic performance and exercise capacity in heart failure with preserved ejection fraction. A... (Review)
Review
This article evaluates the efficacy of using ranolazine to improve diastolic performance and exercise capacity in heart failure with preserved ejection fraction. A comprehensive literature review found eight trials where there are no significant difference in peak O2 (p=0.09) and exercise duration (p=0.18) between ranolazine and placebo. The ranolazine group had significantly higher and better diastolic parameters compared to placebo, with a mean difference of 0.45 (95% CI [27.18-39.50]). There were no significant differences for haemodynamic parameters (blood pressure and heart rate) and electrocardiography (QT interval) between ranolazine and placebo. The review found that ranolazine has good wefficacy to improve diastolic performance among heart failure with preserved ejection fraction patients and it does not affect blood pressure, heart rate and rate of ventricular repolarisation (shortening of the QT interval).
PubMed: 36844933
DOI: 10.15420/ecr.2022.10 -
The Cochrane Database of Systematic... Feb 2017Stable angina pectoris is a chronic medical condition with significant impact on mortality and quality of life; it can be macrovascular or microvascular in origin.... (Review)
Review
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.
Topics: Angina, Stable; Cardiovascular Agents; Cause of Death; Humans; Incidence; Middle Aged; Myocardial Infarction; Quality of Life; Randomized Controlled Trials as Topic; Ranolazine
PubMed: 28178363
DOI: 10.1002/14651858.CD011747.pub2 -
Journal of Arrhythmia Apr 2018Ranolazine is a new medication for the treatment of refractory angina. However, except its anti-anginal properties, it has been found to act as an anti-arrhythmic. The... (Review)
Review
Ranolazine is a new medication for the treatment of refractory angina. However, except its anti-anginal properties, it has been found to act as an anti-arrhythmic. The aim of our systematic review is to present the existing data about the impact of ranolazine in ventricular arrhythmias. We searched MEDLINE and Cochrane databases as well clinicaltrials.gov until September 1, 2017 to find all studies (clinical trials, observational studies, case reports/series) reported data about the impact of ranolazine in ventricular arrhythmias. Our search revealed 14 studies (3 clinical trials, 2 observational studies, 8 case reports, 1 case series). These data reported a beneficial impact of ranolazine in ventricular tachycardia/fibrillation, premature ventricular beats, and ICD interventions in different clinical settings. The existing data highlight the anti-arrhythmic properties of ranolazine in ventricular arrhythmias.
PubMed: 29657587
DOI: 10.1002/joa3.12031 -
Cureus May 2018Postoperative atrial fibrillation (POAF) remains a major risk after cardiac surgery and is associated with an increased risk of stroke, length of stay, mortality, and... (Review)
Review
Postoperative atrial fibrillation (POAF) remains a major risk after cardiac surgery and is associated with an increased risk of stroke, length of stay, mortality, and cost. Ranolazine, an anti-anginal drug, also has anti-arrhythmic properties. The present study is to evaluate the effectiveness of ranolazine in preventing POAF after cardiac surgery. We searched the literature for clinical studies published up to August 2017 with a pre-defined inclusion and exclusion criteria. We identified four studies with a total of 754 patients of which 300 patients received ranolazine; there was a 14% decrease in POAF occurrence following cardiac surgery compared to 32% in the control group. Although ranolazine is an effective therapy in prevention of POAF, larger, multi-center, randomized trials are warranted.
PubMed: 30009098
DOI: 10.7759/cureus.2584 -
Quantitative Imaging in Medicine and... Feb 2024Microvascular dysfunction in patients with nonobstructive coronary artery disease is increasingly being recognized as an important health issue. This systematic review...
Ranolazine for improving coronary microvascular function in patients with nonobstructive coronary artery disease: a systematic review and meta-analysis with a trial sequential analysis of randomized controlled trials.
BACKGROUND
Microvascular dysfunction in patients with nonobstructive coronary artery disease is increasingly being recognized as an important health issue. This systematic review and meta-analysis evaluated the effectiveness of ranolazine, an antianginal agent, in improving coronary microvascular function.
METHODS
We conducted a comprehensive literature search of the Cochrane Library, PubMed, Embase, China National Knowledge Infrastructure, the Chinese BioMedical Literature Database, and gray literature databases until September 30, 2023. The included studies were randomized controlled trials (RCTs) published in the English or Chinese languages that screened for eligibility using two independent investigators. Risk of bias was evaluated with the Cochrane Collaboration tool. Subgroup and sensitivity analyses were used to identify sources of heterogeneity. Meta-analysis was performed using RevMan version 5.4 (Cochrane) and Stata version 16.0 (StataCorp).
RESULTS
From 1,470 citations, 8 RCTs involving 379 participants were included in this analysis. Our findings showed that ranolazine increased coronary flow reserve (CFR) over an 8 to 12-week follow-up period [standardized mean difference =1.16; 95% confidence interval (CI): 0.4-1.89; P=0.002]. Ranolazine increased the global myocardial perfusion reserve index (MPRI) [weighted mean difference (WMD) =0.18; 95% CI: 0.07-0.29; P=0.002] and the midsubendocardial MPRI (WMD =0.10; 95% CI: 0.02-0.19; P=0.02). Moreover, ranolazine improved 3 of the 5 Seattle Angina Questionnaire scores, namely, physical functioning (WMD =4.89; 95% CI: 0.14 to 9.64; P=0.04), angina stability (WMD =17.31; 95% CI: 7.13-27.49; P=0.0009), and quality of life (WMD =10.11; 95% CI: 3.57-16.65; P=0.0003). Trial sequential analysis showed that the meta-analysis of angina stability and quality of life scores had a sufficient sample size and statistical power.
CONCLUSIONS
Our analysis suggests that ranolazine is associated with improvements in CFR, myocardial perfusion, and the Seattle Angina Questionnaire scores in patients with nonobstructive coronary artery disease. However, further large-scale RCTs with long-term follow-up are recommended to validate these findings and provide a more comprehensive understanding of the effects of ranolazine on coronary microvascular function.
PubMed: 38415135
DOI: 10.21037/qims-23-1029 -
European Heart Journal Jan 2019Chronic stable angina is the most prevalent symptom of ischaemic heart disease and its management is a priority. Current guidelines recommend pharmacological therapy...
Chronic stable angina is the most prevalent symptom of ischaemic heart disease and its management is a priority. Current guidelines recommend pharmacological therapy with drugs classified as being first line (beta blockers, calcium channel blockers, short acting nitrates) or second line (long-acting nitrates, ivabradine, nicorandil, ranolazine, and trimetazidine). Second line drugs are indicated for patients who have contraindications to first line agents, do not tolerate them or remain symptomatic. Evidence that one drug is superior to another has been questioned. Between January and March 2018, we performed a systematic review of articles written in English over the past 50 years English-written articles in Medline and Embase following preferred reporting items and the Cochrane collaboration approach. We included double blind randomized studies comparing parallel groups on treatment of angina in patients with stable coronary artery disease, with a sample size of, at least, 100 patients (50 patients per group), with a minimum follow-up of 1 week and an outcome measured on exercise testing, duration of exercise being the preferred outcome. Thirteen studies fulfilled our criteria. Nine studies involved between 100 and 300 patients, (2818 in total) and a further four enrolled greater than 300 patients. Evidence of equivalence was demonstrated for the use of beta-blockers (atenolol), calcium antagonists (amlodipine, nifedipine), and channel inhibitor (ivabradine) in three of these studies. Taken all together, in none of the studies was there evidence that one drug was superior to another in the treatment of angina or to prolong total exercise duration. There is a paucity of data comparing the efficacy of anti-anginal agents. The little available evidence shows that no anti-anginal drug is superior to another and equivalence has been shown only for three classes of drugs. Guidelines draw conclusions not from evidence but from clinical beliefs.
Topics: Adrenergic beta-Antagonists; Angina Pectoris; Calcium Channel Blockers; Cardiovascular Agents; Humans; Nitrates; Randomized Controlled Trials as Topic
PubMed: 30165445
DOI: 10.1093/eurheartj/ehy504 -
Frontiers in Cardiovascular Medicine 2020This study aims to investigate the impact of cardiovascular medications on the coronary flow reserve (CFR) in patients without obstructive coronary artery disease...
Effects of Oral Drugs on Coronary Microvascular Function in Patients Without Significant Stenosis of Epicardial Coronary Arteries: A Systematic Review and Meta-Analysis of Coronary Flow Reserve.
This study aims to investigate the impact of cardiovascular medications on the coronary flow reserve (CFR) in patients without obstructive coronary artery disease (CAD). We searched PubMed, EMBASE, and Cochrane databases from inception to 15 November 2019. Studies were included if they reported CFR from baseline to follow-up after oral drug therapy of patients without obstructive CAD. Data was pooled using random-effects modeling. The primary outcome was change in CFR from baseline to follow-up after oral drug therapy. A total of 46 studies including 845 subjects were included in this study. Relative to baseline, the CFR was improved by angiotensin-converting enzymes (ACEIs), aldosterone receptor antagonists (ARBs) [standard mean difference (SMD): 1.12; 95% CI: 0.77-1.47], and statins treatments (SMD: 0.61; 95%CI: 0.36-0.85). Six to 12 months of calcium channel blocker (CCB) treatments improved CFR (SMD: 1.04; 95% CI: 0.51-1.58). Beta-blocker (SMD: 0.24; 95% CI: -0.39-0.88) and ranolazine treatment (SMD: 0.31; 95% CI: -0.39-1.01) were not associated with improved CFR. Therapy with ACEIs, ARBs, and statins was associated with improved CFR in patients with confirmed or suspicious CMD. CCBs also improved CFR among patients followed for 6-12 months. Beta-blocker and ranolazine had no impact on CFR.
PubMed: 33195465
DOI: 10.3389/fcvm.2020.580419