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Future Cardiology Mar 2022Chronic stable angina pectoris, the most prevalent symptomatic manifestation of coronary artery disease, greatly impairs quality of life and is associated with an... (Review)
Review
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 presence of comorbidities that difficult the use of traditional therapies.
Topics: Acetanilides; Angina, Stable; Coronary Artery Disease; Humans; Piperazines; Quality of Life; Ranolazine
PubMed: 34841884
DOI: 10.2217/fca-2021-0058 -
Journal of the American College of... Mar 2010
Topics: Acetanilides; Acute Coronary Syndrome; Biomarkers; Enzyme Inhibitors; Humans; Natriuretic Peptide, Brain; Piperazines; Ranolazine; Risk Factors
PubMed: 20298925
DOI: 10.1016/j.jacc.2009.10.051 -
International Journal of Women's Health 2017Cardiovascular disease is the leading cause of death in women accounting for 1 in every 4 female deaths. Pathophysiology of ischemic heart disease in women includes... (Review)
Review
Cardiovascular disease is the leading cause of death in women accounting for 1 in every 4 female deaths. Pathophysiology of ischemic heart disease in women includes epicardial coronary artery, endothelial dysfunction, coronary vasospasm, plaque erosion and spontaneous coronary artery dissection. Angina is the most common presentation of stable ischemic heart disease (SIHD) in women. Risk factors for SIHD include traditional risks such as older age, obesity (body mass index [BMI] >25 kg/m), smoking, hypertension, dyslipidemia, cerebrovascular and peripheral vascular disease, sedentary lifestyle, family history of premature coronary artery disease, metabolic syndrome and diabetes mellitus, and nontraditional risk factors, such as gestational diabetes, insulin resistance/polycystic ovarian disease, pregnancy-induced hypertension, pre-eclampsia, eclampsia, menopause, mental stress and autoimmune diseases. Diagnostic testing can be used effectively to risk stratify women. Guidelines-directed medical therapy including aspirin, statins, beta-blocker therapy, calcium channel blockers and ranolazine should be instituted for symptom and ischemia management. Despite robust evidence regarding the adverse outcomes seen in women with ischemic heart disease, knowledge gaps exist in several areas. Future research needs to be directed toward a greater understanding of the role of nontraditional risk factors for SIHD in women, gaining deeper insights into the sex differences in therapeutic effects and formulating a sex-specific algorithm for the management of SIHD in women.
PubMed: 29033611
DOI: 10.2147/IJWH.S107372 -
Turkish Journal of Pharmaceutical... Apr 2022The objective of the current study was to develop an extended release (XR) tablet formulation for ranolazine using Eudragit L 100-55 and hydroxypropylmethylcellulose...
OBJECTIVES
The objective of the current study was to develop an extended release (XR) tablet formulation for ranolazine using Eudragit L 100-55 and hydroxypropylmethylcellulose (HPMC) K100M in an appropriate composition. Ranolazine, an anti-anginal agent, is mainly used for treating chronic stable angina pectoris. The main advantage of this drug that it exhibits anti-ischemic effect, which was not influenced by either blood pressure or heart rate.
MATERIALS AND METHODS
XR tablets of ranolazine were prepared using variable amounts of Eudragit L 100-55 and HPMC K100M in various proportions as 3 factorial design by direct compression technique. The amount of polymers with desired sustained drug release was labeled as factors. On other hand, time taken for drug dissolution was labeled as responses (t, t, t, t).
RESULTS
Nine formulations were obtained as design, developed, and evaluated for quality control parameters. The obtained results clear that all formulations pass the compendial limits. Data obtained from the dissolution study fitted well to kinetic modeling and kinetic parameters were determined. Polynomial equations were derived for responses and checked for validity.
CONCLUSION
RF composed of 31.25 mg of Eudragit L 100-55 and 31.25 mg of HPMC K100M, is the best formulation showing similarity f: 85.78, f: 2.32 with the marketed product (RANEXA). Formulation RF follows zero order, whereas the release mechanism was found to be non-fickian type (n= 0.65).
PubMed: 35509223
DOI: 10.4274/tjps.galenos.2021.58047 -
Journal of Diabetes Research 2021Ranolazine is a second-line drug for the management of chronic coronary syndromes (CCS). Glucose-lowering and endothelial effects have also been reported with this...
BACKGROUND
Ranolazine is a second-line drug for the management of chronic coronary syndromes (CCS). Glucose-lowering and endothelial effects have also been reported with this agent. However, whether ranolazine may improve short-term glycemic variability (GV), strictly related to the prognosis of patients with type 2 diabetes (T2D), is unknown. Thus, we aimed to explore the effects of adding ranolazine to standard anti-ischemic and glucose-lowering therapy on long- and short-term GV as well as on endothelial function and oxidative stress in patients with T2D and CCS.
METHODS
Patients starting ranolazine ( = 16) were evaluated for short-term GV, haemoglobin 1Ac (Hb1Ac) levels, endothelial-dependent flow-mediated vasodilation (FMD), and oxidative stress levels at enrolment and after 3-month follow-up. The same measurements were collected from 16 patients with CCS and T2D that did not receive ranolazine, matched for age, gender, and body mass index.
RESULTS
A significant decline in Hb1Ac levels was reported after 3-month ranolazine treatment (mean change -0.60%; 2-way ANOVA = 0.025). Moreover, among patients receiving ranolazine, short-term GV indexes were significantly improved over time compared with baseline ( = 0.001 for time in range; 2-way ANOVA = 0.010). Conversely, no significant changes were reported in patients without ranolazine. Finally, greater FMD and lower oxidative stress levels were observed in patients on ranolazine at 3 months.
CONCLUSIONS
Ranolazine added to standard anti-ischemic and glucose-lowering therapy demonstrated benefit in improving the glycemic status of patients with T2D and CCS. How this improvement contributes to the overall myocardial benefit of ranolazine requires further studies.
Topics: Analysis of Variance; Diabetes Mellitus; Endothelial Cells; Female; Glycemic Control; Heart Diseases; Humans; Male; Middle Aged; Prospective Studies; Ranolazine; Sodium Channel Blockers; Statistics, Nonparametric
PubMed: 35005029
DOI: 10.1155/2021/4952447 -
Diabetes & Vascular Disease Research Jul 2015Type 2 diabetes mellitus escalates the risk of heart failure partly via its ability to induce a cardiomyopathic state that is independent of coronary artery disease and... (Review)
Review
Type 2 diabetes mellitus escalates the risk of heart failure partly via its ability to induce a cardiomyopathic state that is independent of coronary artery disease and hypertension. Although the pathogenesis of diabetic cardiomyopathy has yet to be fully elucidated, aberrations in cardiac substrate metabolism and energetics are thought to be key drivers. These aberrations include excessive fatty acid utilisation and storage, suppressed glucose oxidation and impaired mitochondrial oxidative phosphorylation. An appreciation of how these abnormalities arise and synergise to promote adverse cardiac remodelling is critical to their effective amelioration. This review focuses on disturbances in myocardial fuel (fatty acids and glucose) flux and energetics in type 2 diabetes, how these disturbances relate to the development of diabetic cardiomyopathy and the potential therapeutic agents that could be used to correct them.
Topics: Antioxidants; Cardiovascular Agents; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Energy Metabolism; Fatty Acids; Glucose; Humans; Mitochondria, Heart; Myocardium; Organophosphorus Compounds; Oxidative Phosphorylation; Oxidative Stress; Perhexiline; Ranolazine; Trimetazidine; Ubiquinone
PubMed: 25941161
DOI: 10.1177/1479164115580936 -
Journal of Arrhythmia Jun 2017Atrial fibrillation (AF) is a common complication after cardiac surgery. Ranolazine is a Food and Drug Administration approved anti-ischemic drug, which also has... (Review)
Review
BACKGROUND
Atrial fibrillation (AF) is a common complication after cardiac surgery. Ranolazine is a Food and Drug Administration approved anti-ischemic drug, which also has anti-arrhythmic properties. Recent studies have demonstrated the benefit of ranolazine in preventing post-operative AF (POAF) in patients undergoing cardiac surgery. Hence, we performed a meta-analysis of published studies comparing ranolazine plus standard therapy versus standard therapy for POAF prevention in patients undergoing cardiac surgery.
METHODS
We performed a comprehensive search of Medline, Google Scholar, PubMed, abstracts from annual scientific sessions, and Cochrane library database for studies that assessed the effectiveness of ranolazine plus standard therapy by comparing it with standard therapy alone in preventing POAF in patients undergoing cardiac surgery. From all the studies, data on POAF events among groups were collected, and the random-effects (DerSimonian and Laird) method was used for meta-analysis.
RESULTS
Four studies with 663 patients were included in the final analysis, with 300 and 363 patients in the ranolazine plus standard therapy and standard therapy groups, respectively. The types of cardiac surgeries were coronary artery bypass grafting (CABG), valve surgery or combination of CABG, and valve surgeries. After pooled analysis, ranolazine plus standard therapy was associated with a significant reduction in POAF events compared to standard therapy alone (risk ratio=0.44 [0.25, 0.78], -value=0.005). There was no difference in adverse events between the two therapies. However, in one study, more patients in the ranolazine group had transient symptomatic hypotension after the surgery.
CONCLUSIONS
Ranolazine may prove beneficial in POAF prevention following cardiac surgeries. Although the pooled treatment effect is quite impressive with a reduction of more than 50% of risk of developing POAF, small number of studies and variation in ranolazine dose regimen in each study make our results inconclusive, but worthy of further investigation. That is why this result has to be interpreted as only hypothesis generating, rather than conclusion drawing.
PubMed: 28607609
DOI: 10.1016/j.joa.2016.10.563 -
Dermatology Reports Mar 2022Dermatoses affecting palms may represent a dermatologic challenge from both the diagnostic, and therapeutic point of view. Patients with supposedly occupational...
Dermatoses affecting palms may represent a dermatologic challenge from both the diagnostic, and therapeutic point of view. Patients with supposedly occupational dermatitis can spend months or even years in a frustrating attempt to avoid contact with possible irritants or allergens. To underline the importance of a thorough unbiased analysis of the patient's history and clinical features, we present the iconic case of a bricklayer affected by a chronic, disabling desquamation of palms which in the end was classified as keratolysis exfoliativa (KE) attributed to ranolazine-intake, an antianginal drug. To the best of our knowledge, this specific adverse effect of druginduced KE of palms has never been reported before in association with ranolazine.
PubMed: 35399369
DOI: 10.4081/dr.2022.9264 -
Circulation Jan 2024Angina with nonobstructive coronary arteries is a common condition for which no effective treatment has been established. We hypothesized that the measurement of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Angina with nonobstructive coronary arteries is a common condition for which no effective treatment has been established. We hypothesized that the measurement of coronary flow reserve (CFR) allows identification of patients with angina with nonobstructive coronary arteries who would benefit from anti-ischemic therapy.
METHODS
Patients with angina with nonobstructive coronary arteries underwent blinded invasive CFR measurement and were randomly assigned to receive 4 weeks of amlodipine or ranolazine. After a 1-week washout, they crossed over to the other drug for 4 weeks; final assessment was after the cessation of study medication for another 4 weeks. The primary outcome was change in treadmill exercise time, and the secondary outcome was change in Seattle Angina Questionnaire summary score in response to anti-ischemic therapy. Analysis was on a per protocol basis according to the following classification: coronary microvascular disease (CMD group) if CFR<2.5 and reference group if CFR≥2.5. The study protocol was registered before the first patient was enrolled (International Standard Randomised Controlled Trial Number: ISRCTN94728379).
RESULTS
Eighty-seven patients (61±8 years of age; 62% women) underwent random assignment (57 CMD group and 30 reference group). Baseline exercise time and Seattle Angina Questionnaire summary scores were similar between groups. The CMD group had a greater increment (delta) in exercise time than the reference group in response to both amlodipine (difference in delta, 82 s [95% CI, 37-126 s]; <0.001) and ranolazine (difference in delta, 68 s [95% CI, 21-115 s]; =0.005). The CMD group reported a greater increment (delta) in Seattle Angina Questionnaire summary score than the reference group in response to ranolazine (difference in delta, 7 points [95% CI, 0-15]; =0.048), but not to amlodipine (difference in delta, 2 points [95% CI, -5 to 8]; =0.549).
CONCLUSIONS
Among phenotypically similar patients with angina with nonobstructive coronary arteries, only those with an impaired CFR derive benefit from anti-ischemic therapy. These findings support measurement of CFR to diagnose and guide management of this otherwise heterogeneous patient group.
Topics: Female; Humans; Male; Amlodipine; Coronary Artery Disease; Coronary Circulation; Cross-Over Studies; Microcirculation; Microvascular Angina; Myocardial Ischemia; Phenotype; Ranolazine; Middle Aged; Aged
PubMed: 37905403
DOI: 10.1161/CIRCULATIONAHA.123.066680 -
Journal of the American Heart... Mar 2016
Review
Topics: Angina, Stable; Animals; Cardiovascular Agents; Chronic Disease; Drug Interactions; Drug Labeling; Humans; Off-Label Use; Practice Guidelines as Topic; Ranolazine; Sodium Channel Blockers; Treatment Outcome
PubMed: 26979079
DOI: 10.1161/JAHA.116.003196