The place of ranolazine in modern pharmacotherapy of chronic coronary syndrome. Own experience Review article
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Published:
Jun 30, 2025
Keywords:
adherence, arrhythmia, chronic coronary syndrome, ranolazine, type 2 diabetes
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Abstract
Ranolazine is an antianginal drug with a multifaceted mechanism of action that complements the effects of conventional pharmacotherapy for chronic coronary syndrome. The primary mechanism of its action stems from the inhibition of the late sodium current in the cardiomyocyte cell membrane. This results in improved myocardial relaxation and compliance, thereby reducing the frequency of observed arrhythmias. The specific antiarrhythmic mechanism of ranolazine prolongs the action potential duration and decreases the electrical excitability of cardiac muscle cells. Additionally, ranolazine exerts a cardioprotective effect under ischemic conditions. It inhibits β-oxidation of fatty acids, leading to a predominance of glucose metabolism. The drug is well-tolerated by patients, and its efficacy led to its inclusion in 2018 in the classification of medications used for supraventricular and ventricular arrhythmias.
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Grabysa, R., & Ciołek, A. (2025). The place of ranolazine in modern pharmacotherapy of chronic coronary syndrome. Own experience. Medycyna Faktow (J EBM), 18(2(67), 296-303. https://doi.org/10.24292/01.MF.0225.19
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References
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14. De Ferrari GM, Maier LS, Mont L et al. Ranolazine in the treatment of atrial fibrillation: Results of the dose-ranging RAFFAELLO (Ranolazine in Atrial Fibrillation Following An ELectricaL CardiOversion) study. Heart Rhythm. 2015; 12(5): 872-8. http://doi.org/10.1016/j.hrthm.2015.01.021.
15. Koskinas KC, Fragakis N, Katritsis D et al. Ranolazine enhances the efficacy of amiodarone for conversion of recent-onset atrial fibrillation. Europace. 2014; 16(7): 973-9. http://doi.org/10.1093/europace/eut407.
16. Timmis AD, Chaitman BR, Crager M. Effects of ranolazine on exercise tolerance and HbA1c in patients with chronic angina and diabetes. Eur Heart J. 2006; 27(1): 42-8. http://doi.org/10.1093/eurheartj/ehi495.
17. Morrow DA, Scirica BM, Chaitman BR et al. Evaluation of the glycometabolic effects of ranolazine in patients with and without diabetes mellitus in the MERLIN-TIMI 36 randomized controlled trial. Circulation. 2009; 119(15): 2032-9. http://doi.org/10.1161/CIRCULATIONAHA.107.763912.
18. Teoh IH, Banerjee M. Effect of ranolazine on glycaemia in adults with and without diabetes: a meta-analysis of randomised controlled trials. Open Heart. 2018; 5(2): e000706. http://doi.org/10.1136/openhrt-2017-000706.
19. Dhalla AK, Yang M, Ning Y et al. Blockade of Na+ channels in pancreatic α-cells has antidiabetic effects. Diabetes. 2014; 63(10): 3545-56. http://doi.org/10.2337/db13-1562.
20. Morrow DA, Scirica BM, Sabatine MS et al. B-type natriuretic peptide and the effect of ranolazine in patients with non-ST-segment elevation acute coronary syndromes: observations from the MERLIN-TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary-Thrombolysis In Myocardial Infarction 36) trial. J Am Coll Cardiol. 2010; 55(12): 1189-96. http://doi.org/10.1016/j.jacc.2009.09.068.
21. Cempaka Putri DKS, Andrianto A, Al-Farabi MJ et al. Efficacy of Ranolazine to Improve Diastolic Performance in Heart Failure with Preserved Ejection Fraction: A Systematic Review and Meta-analysis. Eur Cardiol. 2023; 18: e02. http://doi.org/10.15420/ecr.2022.10.
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23. Kofler T, Hess S, Moccetti F et al. Efficacy of Ranolazine for Treatment of Coronary Microvascular Dysfunction – A Systematic Review and Meta-analysis of Randomized Trials. CJC Open. 2021; 3(1): 101-8. http://doi.org/10.1016/j.cjco.2020.09.005.
24. Ahmed B, Mondragon J, Sheldon M et al. Impact of ranolazine on coronary microvascular dysfunction (MICRO) study. Cardiovasc Revasc Med. 2017; 18(6): 431-5. http://doi.org/10.1016/j.carrev.2017.04.012.
25. Ling H, Fu S, Xu M et al. 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. Quant Imaging Med Surg. 2024; 14(2): 1451-65. http://doi.org/10.21037/qims-23-1029.
26. Ferrari R, Ford I, Fox K et al. Efficacy and safety of trimetazidine after percutaneous coronary intervention (ATPCI): a randomised, double-blind, placebo-controlled trial. The Lancet. 2020; 396(10254): 830-8. http://doi.org/10.1016/S0140-6736(20)31790-6.
27. Koren MJ, Crager MR, Sweeney M. Long-term safety of a novel antianginal agent in patients with severe chronic stable angina: the Ranolazine Open Label Experience (ROLE). J Am Coll Cardiol. 2007; 49(10): 1027-34. http://doi.org/10.1016/j.jacc.2006.10.067.
2. NFZ o Zdrowiu. Choroba Niedokrwienna Serca. 2020 .
3. Vrints C, Andreotti F, Koskinas KC et al. 2024 ESC Guidelines for the management of chronic coronary syndromes: Developed by the task force for the management of chronic coronary syndromes of the European Society of Cardiology (ESC) Endorsed by the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2024; 45(36): 3415-37. http://doi.org/10.1093/eurheartj/ehae177.
4. Eisen A, Bhatt DL, Steg PG et al. Angina and Future Cardiovascular Events in Stable Patients With Coronary Artery Disease: Insights From the Reduction of Atherothrombosis for Continued Health (REACH) Registry. J Am Heart Assoc. 2016; 5(10): e004080. http://doi.org/10.1161/JAHA.116.004080.
5. Virani SS, Newby LK, Arnold SV et al. 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. Circulation. 2023; 148(9): e9-e119. http://doi.org/10.1161/CIR.0000000000001168.
6. Antzelevitch C, Belardinelli L, Zygmunt AC et al. Electrophysiological effects of ranolazine, a novel antianginal agent with antiarrhythmic properties. Circulation. 2004; 110(8): 904-10. http://doi.org/10.1161/01.CIR.0000139333.83620.5D.
7. Fraser H, Belardinelli L, Wang L et al. Ranolazine decreases diastolic calcium accumulation caused by ATX-II or ischemia in rat hearts. J Mol Cell Cardiol. 2006; 41(6): 1031-8. http://doi.org/10.1016/j.yjmcc.2006.08.012.
8. Kusz B, Mizia-Stec K. Ranolazine – a new antiarrhythmic agent? WDR. 2015; 2(35): 4-9. http://doi.org/10.5604/18967892.1154001.
9. Lei M, Wu L, Terrar DA et al. Modernized Classification of Cardiac Antiarrhythmic Drugs. Circulation. 2018; 138(17): 1879-96. http://doi.org/10.1161/CIRCULATIONAHA.118.035455.
10. Belardinelli L, Shryock JC, Fraser H. Inhibition of the late sodium current as a potential cardioprotective principle: effects of the late sodium current inhibitor ranolazine. Heart Br Card Soc. 2006; 92 Suppl 4(Suppl 4): iv6-iv14. http://doi.org/10.1136/hrt.2005.078790.
11. Chaitman BR, Skettino SL, Parker JO et al. Anti-ischemic effects and long-term survival during ranolazine monotherapy in patients with chronic severe angina. J Am Coll Cardiol. 2004; 43(8): 1375-82. http://doi.org/10.1016/j.jacc.2003.11.045.
12. Sendon JL, Lee S, Cheng ML et al. Effects of ranolazine on exercise tolerance and angina frequency in patients with severe chronic angina receiving maximally-tolerated background therapy: analysis from the Combination Assessment of Ranolazine In Stable Angina (CARISA) randomized trial. Eur J Prev Cardiol. 2012; 19(5): 952-9. http://doi.org/10.1177/2047487312450133.
13. Scirica BM, Morrow DA, Hod H et al. Effect of ranolazine, an antianginal agent with novel electrophysiological properties, on the incidence of arrhythmias in patients with non ST-segment elevation acute coronary syndrome: results from the Metabolic Efficiency With Ranolazine for Less Ischemia in Non ST-Elevation Acute Coronary Syndrome Thrombolysis in Myocardial Infarction 36 (MERLIN-TIMI 36) randomized controlled trial. Circulation. 2007; 116(15): 1647-52. http://doi.org/10.1161/CIRCULATIONAHA.107.724880.
14. De Ferrari GM, Maier LS, Mont L et al. Ranolazine in the treatment of atrial fibrillation: Results of the dose-ranging RAFFAELLO (Ranolazine in Atrial Fibrillation Following An ELectricaL CardiOversion) study. Heart Rhythm. 2015; 12(5): 872-8. http://doi.org/10.1016/j.hrthm.2015.01.021.
15. Koskinas KC, Fragakis N, Katritsis D et al. Ranolazine enhances the efficacy of amiodarone for conversion of recent-onset atrial fibrillation. Europace. 2014; 16(7): 973-9. http://doi.org/10.1093/europace/eut407.
16. Timmis AD, Chaitman BR, Crager M. Effects of ranolazine on exercise tolerance and HbA1c in patients with chronic angina and diabetes. Eur Heart J. 2006; 27(1): 42-8. http://doi.org/10.1093/eurheartj/ehi495.
17. Morrow DA, Scirica BM, Chaitman BR et al. Evaluation of the glycometabolic effects of ranolazine in patients with and without diabetes mellitus in the MERLIN-TIMI 36 randomized controlled trial. Circulation. 2009; 119(15): 2032-9. http://doi.org/10.1161/CIRCULATIONAHA.107.763912.
18. Teoh IH, Banerjee M. Effect of ranolazine on glycaemia in adults with and without diabetes: a meta-analysis of randomised controlled trials. Open Heart. 2018; 5(2): e000706. http://doi.org/10.1136/openhrt-2017-000706.
19. Dhalla AK, Yang M, Ning Y et al. Blockade of Na+ channels in pancreatic α-cells has antidiabetic effects. Diabetes. 2014; 63(10): 3545-56. http://doi.org/10.2337/db13-1562.
20. Morrow DA, Scirica BM, Sabatine MS et al. B-type natriuretic peptide and the effect of ranolazine in patients with non-ST-segment elevation acute coronary syndromes: observations from the MERLIN-TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary-Thrombolysis In Myocardial Infarction 36) trial. J Am Coll Cardiol. 2010; 55(12): 1189-96. http://doi.org/10.1016/j.jacc.2009.09.068.
21. Cempaka Putri DKS, Andrianto A, Al-Farabi MJ et al. Efficacy of Ranolazine to Improve Diastolic Performance in Heart Failure with Preserved Ejection Fraction: A Systematic Review and Meta-analysis. Eur Cardiol. 2023; 18: e02. http://doi.org/10.15420/ecr.2022.10.
22. McDonagh TA, Metra M, Adamo M et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). With the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2022; 24(1): 4-131. http://doi.org/10.1002/ejhf.2333.
23. Kofler T, Hess S, Moccetti F et al. Efficacy of Ranolazine for Treatment of Coronary Microvascular Dysfunction – A Systematic Review and Meta-analysis of Randomized Trials. CJC Open. 2021; 3(1): 101-8. http://doi.org/10.1016/j.cjco.2020.09.005.
24. Ahmed B, Mondragon J, Sheldon M et al. Impact of ranolazine on coronary microvascular dysfunction (MICRO) study. Cardiovasc Revasc Med. 2017; 18(6): 431-5. http://doi.org/10.1016/j.carrev.2017.04.012.
25. Ling H, Fu S, Xu M et al. 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. Quant Imaging Med Surg. 2024; 14(2): 1451-65. http://doi.org/10.21037/qims-23-1029.
26. Ferrari R, Ford I, Fox K et al. Efficacy and safety of trimetazidine after percutaneous coronary intervention (ATPCI): a randomised, double-blind, placebo-controlled trial. The Lancet. 2020; 396(10254): 830-8. http://doi.org/10.1016/S0140-6736(20)31790-6.
27. Koren MJ, Crager MR, Sweeney M. Long-term safety of a novel antianginal agent in patients with severe chronic stable angina: the Ranolazine Open Label Experience (ROLE). J Am Coll Cardiol. 2007; 49(10): 1027-34. http://doi.org/10.1016/j.jacc.2006.10.067.