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Objectives: We assessed the efficacy and safety of ranolazine in real-world patients with hypertrophic cardiomyopathy (HCM)., Background: Ranolazine is an anti-anginal drug that inhibits the late phase of the inward sodium current. In a small prospective trial, ranolazine reduced the arrhythmic burden and improved biomarker profile in HCM patients. However, systematic reports reflecting real-world use in this setting are lacking., Methods: Changes in clinical and instrumental features, symptoms and arrhythmic burden were evaluated in 119 patients with HCM before and during treatment with ranolazine at a national referral centre for HCM., Results: Patients were treated with ranolazine for 2 [1-4] years; 83 (70%) achieved a dosage ≥1000 mg per day. Treatment interruption was necessary in 24 patients (20%) due to side effects (n = 10, 8%) or disopyramide initiation (n = 8, 7%). Seventy patients (59%) were treated with ranolazine for relief of angina. Among them, 51 (73%) had total symptomatic relief and 47 patients (67%) showed ≥2 Canadian Cardiovascular society (CCS) angina grade improvement. Sixteen patients (13%) were treated for recurrent ventricular arrhythmias, including 4 with a clear ischemic trigger, who experienced no further arrhythmic episodes while on ranolazine. Finally, 33 patients (28%) were treated for heart failure associated with severe diastolic dysfunction: no symptomatic benefit could be observed in this group., Conclusion: Ranolazine was safe and well tolerated in patients with HCM. The use of ranolazine may be considered in patients with HCM and microvascular angina., Competing Interests: Declaration of Competing Interest Prof. Olivotto is in the advisory board and had research grant from BMS-Myokardia, Cytokinetics, Boston Scientific, Sanofi Genzyme, Shire Takeda, Amicus, Menarini International, Bayer, Tenaya., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: More than 20% of patients presenting to the catheterization lab have no significant obstructive coronary artery disease (CAD) despite having angina. Several occult coronary abnormalities, including endothelial dysfunction, microvascular dysfunction (MVD), and/or a myocardial bridge (MB), may explain their symptoms. We studied the effect of ranolazine on symptoms and quality of life (QOL) in these patients., Methods: We retrospectively studied 53 patients prescribed with ranolazine, matched on sex and age, with 106 patients on standard of care who underwent comprehensive invasive testing. Endothelial dysfunction was defined as a decrease in luminal diameter of >20% after intracoronary acetylcholine, MVD as an index of microvascular resistance ≥25, and a MB as an echolucent half-moon sign and/or ≥10% systolic compression on intravascular ultrasound. A Seattle Angina Questionnaire (SAQ) and SF-12 questionnaire were completed at baseline and follow-up., Results: Median follow-up was 1.9 (1.7-2.2) years. Endothelial dysfunction was present in 109 (69%), MVD in 36 (23%), and an MB in 86 (54%). Both groups had significant improvement in all dimensions of the SF-12 and SAQ with the exception of treatment satisfaction. We found no significant difference in change in SAQ and SF-12 scores between the groups, although the ranolazine group had significantly lower baseline SAQ scores., Conclusion: In patients with angina and no obstructive CAD, ranolazine is no different than standard of care in symptomatic and QOL improvement. Further randomized trials are warrented to confirm our findings and identify novel medical therapies in this patient population., Competing Interests: Declaration of competing interest No conflict of interest., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Type 2 diabetes (T2D) is associated with a high burden of angina. Ranolazine has been shown to reduce angina frequency versus placebo in patients with T2D and stable angina. We sought to estimate the cost-effectiveness of ranolazine when added to standard-of-care (SoC) versus SoC alone in patients with T2D and stable, but symptomatic coronary disease despite treatment with 1-2 antianginals., Methods: A Markov model was developed and evaluated using cohort simulation. The model utilized a US societal perspective, 1-month cycle length and 1-year time horizon and was developed to estimate the cost-effectiveness of ranolazine versus SoC. Patients entered the model in 1 of 4 angina frequency health states based on baseline Seattle Angina Questionnaire Angina Frequency scores (100 = no; 61-99 = monthly; 31-60 = weekly; 0-30 = daily) and could transition between health states (first cycle only) or to death (any cycle) based on probabilities derived from the Type 2 Diabetes Evaluation of Ranolazine in Subjects with Chronic Stable Angina trial., Results: Our model estimated patients treated with ranolazine lived a mean of 0.728 quality adjusted life years (QALYs) at a cost of $16,654. Those not receiving ranolazine lived a mean of 0.702 QALYs and incurred costs of $15,476. The incremental cost-effectiveness ratio for the addition of ranolazine to SoC was $45,308/QALY. Short Form-36 data suggest improvements in patients' bodily pain drove the gain in QALYs associated with ranolazine (2.73 versus 3.96, p = 0.01)., Conclusion: Our model suggests the addition of ranolazine to SoC is likely cost-effective from a US societal perspective for the treatment of patients with T2D and stable, symptomatic coronary disease despite treatment with 1-2 antianginals., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background/objectives: Available pharmacological options for rhythm control strategy in atrial fibrillation (AF) are limited by sub-optimal efficacy and potentially serious adverse events. The aim of the present meta-analysis is to determine the efficacy and safety of ranolazine for AF management., Methods: The present meta-analysis was conducted according to current recommendations (CRD42016039000). Two large medical databases (MEDLINE and Scopus) were systematically searched and from that eight randomized clinical trials and two non-randomized observational studies were identified. The primary endpoint was to determine the efficacy of ranolazine to prevent AF episodes. Secondary efficacy endpoints were: efficacy in converting AF to sinus rhythm, time to conversion, and reduction in AF burden. Safety endpoints included death, serious adverse events, and QTc prolongation., Results: Ranolazine was found to be effective in reducing the risk of AF when compared to control (OR 0.47; 95% CI 0.29-0.76; p=0.003). Subgroup analysis showed a larger effect size in post-operative AF (OR 0.29; 95% CI 0.11-0.77; p=0.03) when compared to no post-operative AF (OR 0.70; 95% CI 0.54-0.83; p=0.005). Ranolazine increased the chances of successful cardioversion when added to amiodarone over amiodarone alone (OR 3.11; 95% CI 1.42-6.79; p=0.004) while significantly reducing time to conversion (SMD -2.83h; 95% CI -4.69--0.97h; p<0.001). Overall risks of death, adverse events, and QTc prolongation were comparable between ranolazine and control group., Conclusions: Ranolazine is an effective option when used for rhythm control strategy in AF. The use of ranolazine seems to be safe and associated with few adverse events., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Ranolazine was FDA approved for chronic angina in 2006. Since then, there has been extensive research involving this drug. The mechanism of action, debatable at the time of approval, has been demonstrated. Ranolazine acts via inhibition of late sodium channel current in the myocardium. This acts by lowering abnormally high cytosolic calcium levels. Other possible clinical applications of Ranolazine have also been explored. Out of many lines of investigation, its effects in atrial fibrillation, especially post-CABG and recurrent atrial fibrillation show promise. It has also shown definite HbA1c lowering effects when used in diabetics with coronary artery disease. Other possible indications for the drug include pulmonary arterial hypertension, diastolic dysfunction and chemotherapy-induced cardiotoxicity. This review aims to summarize major research regarding Ranolazine in potential applications beyond chronic angina. There are few dedicated large, randomized, phase III trials exploring the newer effects of Ranolazine. There are a few such trials underway, but more are needed., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: The aim of this pilot study was to evaluate if ranolazine (R) could improve insulin resistance (IR) in obese/overweight non-diabetic patients with coronary heart disease (CHD)., Methods: The study enrolled 40 patients with already diagnosed CHD, previous revascularization, residual ischemia at ergometric test and IR. Mean age was 62.4±9years, M/F=31/9. Patients were randomly assigned to one of the two following groups: group 1 (20 patients) started R at dose of 500mg/bid; group 2 (20 patients) increased the dose of beta/blockers or calcium-channel blockers without introducing R. IR was defined as having HOMA-IR>2.5. At baseline and after 12weeks, all subjects performed an ergometric test and 12h fasting blood sample collection for determining glucose and insulin levels., Results: At 12weeks follow-up visit HOMA-IR significantly decreased in group 1 (from 3.1±1.7 to 2.3±0.9; p=0.02) while it remained unchanged in group 2 (from 3.0±1.4 to 2.8±1.2; p=0.14) (between groups p=0.009). At 12weeks follow-up visit patients of both groups obtained a significant increase of ischemic threshold at ergometric test, compared to baseline, (group 1 from 308.4±45s to 423.9±57s, p=0.0004); (group 1 from 315.7±63s to 441.2±51s, p=0.0001); without between groups difference (p=0.25)., Conclusions: Our data suggest that starting R, instead of increasing the dose of beta-blockers/calcium-channel blockers, could be a preferable choice in obese/overweight CHD subjects with residual ischemia after revascularization., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

To conduct a systematic review of the evidence regarding the economic value of ranolazine relative to standard-of-care (SOC) for the treatment of symptomatic chronic stable angina (CSA). Electronic databases were searched using relevant keywords. The identified studies were independently reviewed by two investigators against pre-determined inclusion and exclusion criteria. Their data were extracted using a relevant form and consequently were synthesized. Studies were also evaluated using the Quality of Health Economic Studies scale. The main outcomes considered were the cost and effectiveness for each comparator and the incremental cost per quality-adjusted-life year (QALY) gained. Six studies were included in the review. Five of these assessed the cost-utility of ranolazine added to SOC, compared to SOC alone, using decision trees or Markov models whereas one was a retrospective cost evaluation study. The analysis was conducted from a payer perspective in five studies and from a societal perspective in one study with the time horizon varying between six months and a year. The incremental cost-effectiveness ratio (ICER), ranged from €4000 to €15,000 per QALY gained. Ranolazine appears to be dominant or cost-effective, mainly due to its ability to decrease angina-related hospitalizations and also due to a marginal improvement in quality of life. The acquisition cost of ranolazine was the variable with the greatest impact upon the ICER. The existing evidence, although limited, indicates that ranolazine may be a dominant or cost-effective therapy option, for the treatment of patients with symptomatic CSA. Further research is required to evaluate the cost-effectiveness of ranolazine., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objective: Primary objectives were to evaluate tolerability, compliance, and perception of ranolazine effectiveness for chronic stable angina in a routine clinical setting. The secondary objective was safety evaluation., Methods: Prospective, multi-centre, observational, study with a 6-month follow-up and study visits at baseline, 3- and 6 months in patients with chronic stable angina. Ranolazine was administered according to the summary of product characteristics and investigator discretion. Data was collected on patient and disease characteristics, concomitant therapy, angina frequency and severity, quality of life (QoL), perception of effectiveness, compliance, and adverse events., Results: Between July 2010 and July 2012, 189 patients were enrolled at 20 centres. Ranolazine decreased the proportion of patients experiencing angina attacks from 88.4% at baseline to 26.5% at 6 months (p<0.001). Heart rate and blood pressure were not appreciably affected. The proportion of patients without symptoms on normal exertion (Canadian Cardiovascular Society grading class I) increased from 22.3% to 75.3% (p<0.001); patients reporting limitations in daily activities decreased from 80.4% to 35.5%. (p<0.001). Patient- and physician-assessed QoL improved (both p<0.001). Therapeutic efficacy was rated "good" or "very good" in 67.7% of cases by physicians, and by 63.5% of the patients. Physicians rated compliance "good" or "very good" in 73.5% of cases. Adverse events were consistent with previous reports, and consisted of 40 events in 24 patients; 12 were serious., Conclusions: Ranolazine was associated with decreased angina frequency and severity, and improvements in QoL. The benefits provided by ranolazine in controlled clinical trials are maintained in the clinical setting., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Ranolazine is a novel well-tolerated anti-ischemic drug, which selectively inhibits late sodium current and exerts metabolic properties without any hemodynamic effect. Ranolazine has been approved as a second-line medical treatment for symptomatic stable coronary artery disease. Primary microvascular angina (MVA) is suspected when angina symptoms occur in patients with demonstrated myocardial ischemia, absence of myocardial disease and normal coronary artery angiography. Recent clinical data suggest that MVA represents a complex entity, which has been increasingly recognized as a significant cause of morbidity. High variability and low response to traditional anti-anginal treatment characterize primary MVA. Despite the fact that clinical and preclinical evidence provides information regarding ranolazine usefulness in primary MVA management, only three recent small randomized trials have investigated this issue. By selecting peer-reviewed literature in Pubmed and Cochrane Library, this review provides an overview on ranolazine pharmacology and efficacy, focusing on recent evidence suggesting its usefulness in management of primary MVA., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)