Research Article| Volume 169, ISSUE 4, P262-270, November 15, 2013

Download started.


Effects of ranolazine in symptomatic patients with stable coronary artery disease. A systematic review and meta-analysis

Published:September 23, 2013DOI:



      Ranolazine (R), as add-on therapy in symptomatic patients with chronic stable coronary artery disease (CAD), has been tested in randomized clinical studies. Aim of the study was to assess in a meta-analysis the effects of R on angina, nitroglycerin consumption, functional capacity, electrocardiographic signs of ischemia and hemodynamic parameters in patients with chronic CAD.


      Randomized trials assessing the effects of R compared to control on exercise duration, time to onset of angina, time to 1 mm ST-segment depression, weekly nitroglycerin consumption and weekly angina frequency were included in the analysis. The effects of R compared to control on heart rate and blood pressure were also analyzed.


      Six trials enrolling 9223 patients were included in the analysis. At trough and peak levels, R compared to control significantly improved exercise duration, time to onset of angina and time to 1 mm ST-segment depression. Additionally, R compared to control significantly reduced weekly angina frequency and weekly nitroglycerin consumption. Finally, R compared to control did not significantly reduce supine systolic and diastolic blood pressure as well as heart rate, standing heart rate and diastolic blood pressure, whereas it modestly reduced standing systolic blood pressure. At sensitivity analysis, results were not influenced by concomitant background therapy.


      In symptomatic patients with chronic CAD, R, added to conventional therapy, effectively reduces angina frequency and sublingual nitroglycerin consumption while prolonging exercise duration as well as time to onset of ischemia and to onset of angina with no substantial effects on blood pressure and heart rate.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to International Journal of Cardiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Holubkov R.
        • Laskey W.K.
        • Haviland A.
        • et al.
        Angina 1 year after percutaneous coronary intervention: a report from the NHLBI Dynamic Registry.
        Am Heart J. 2002; 144: 826-833
        • Weintraub W.S.
        • Spertus J.A.
        • Kolm P.
        • et al.
        Effect of PCI on quality of life in patients with stable coronary disease.
        N Engl J Med. 2008; 359: 677-687
        • Vieira R.D.
        • Hueb W.
        • Hlatky M.
        • et al.
        Cost-effectiveness analysis for surgical, angioplasty, or medical therapeutics for coronary artery disease: 5-year follow-up of medicine, angioplasty, or surgery study (MASS) II trial.
        Circulation. 2012; 126: S145-S150
        • Arnold S.V.
        • Morrow D.A.
        • Lei Y.
        • et al.
        Economic impact of angina after an acute coronary syndrome: insights from the MERLIN-TIMI 36 trial.
        Circ Cardiovasc Qual Outcomes. 2009; 2: 344-353
        • Arnold S.V.
        • Morrow D.A.
        • Wang K.
        • et al.
        Effects of ranolazine on disease-specific health status and quality of life among patients with acute coronary syndromes: results from the MERLIN-TIMI 36 randomized trial.
        Circ Cardiovasc Qual Outcomes. 2008; 1: 107-115
      1. Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS); European Association for Percutaneous Cardiovascular Interventions (EAPCI). Guidelines on myocardial revascularization.
        Eur Heart J. 2010; 31: 2501-2555
        • Boden W.E.
        • O'Rourke R.A.
        • Teo K.K.
        • et al.
        Optimal medical therapy with or without PCI for stable coronary disease.
        N Engl J Med. 2007; 356: 1503-1516
        • Chaitman B.R.
        Ranolazine for the treatment of chronic angina and potential use in other cardiovascular conditions.
        Circulation. 2006; 113: 2462-2472
        • Moher D.
        • Liberati A.
        • Tetzlaff J.
        Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.
        J Clin Epidemiol. 2009; 62: 1006-1012
        • Detsky A.S.
        • Naylor C.D.
        • O'Rourke K.
        • McGeer A.J.
        • L'Abbé K.A.
        Incorporating variations in the quality of individual randomized trials into meta-analysis.
        J Clin Epidemiol. 1992; 45: 255-265
        • Savarese G.
        • Costanzo P.
        • Cleland J.G.
        • et al.
        A meta-analysis reporting effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in patients without heart failure.
        J Am Coll Cardiol. 2013; 61: 131-142
        • Costanzo P.
        • Perrone-Filardi P.
        • Petretta M.
        • et al.
        Calcium channel blockers and cardiovascular outcomes: a meta-analysis of 175,634 patients.
        J Hypertens. 2009; 27: 1136-1151
      2. Higgins J.P.T. Deeks J.J. Chapter 7: selecting studies and collecting data. Cochrane handbook for systematic reviews of interventions. 2011 ([(Version 5.1.0 (updated March 2011). The Cochrane Collaboration. Available from])
        • Sharp S.
        • Sterne J.
        STB Rep. 1998; 7: 100-109
      3. Deeks J.J. Higgins J.P.T. Altman D.G. Chapter 9: Analysing data and undertaking meta-analyses. Cochrane handbook for systematic reviews of interventions. 2011 ([Version 5.1.0 (updated March 2011). The Cochrane Collaboration. Available from])
        • Tobias A.
        Assessing the influence of a single study in meta-analysis.
        STB. 1999; 47: 15-17
        • Sharp S.J.
        Meta-analysis regression.
        STB. 1998; 42: 16-22
        • Thompson S.G.
        • Sharp S.J.
        Explaining heterogeneity in meta-analysis: a comparison of methods.
        Stat Med. 1999; 18: 2693-2708
        • Egger M.
        • Davey Smith G.
        • Schneider M.
        • Minder C.
        Bias in metaanalysis detected by a simple, graphical test.
        BMJ. 1997; 315: 629-634
        • Chaitman B.R.
        • Skettino S.L.
        • Parker J.O.
        • et al.
        Anti-ischemic effects and long-term survival during ranolazine monotherapy in patients with chronic severe angina.
        J Am Coll Cardiol. 2004; 43: 1375-1382
        • Chaitman B.R.
        • Pepine C.J.
        • Parker J.O.
        • et al.
        Effects of ranolazine with atenolol, amlodipine, or diltiazem on exercise tolerance and angina frequency in patients with severe chronic angina: a randomized controlled trial.
        JAMA. 2004; 291: 309-316
        • Timmis A.D.
        • Chaitman B.R.
        • Crager M.
        Effects of ranolazine on exercise tolerance and HbA1c in patients with chronic angina and diabetes.
        Eur Heart J. 2006; 27: 42-48
        • Rousseau M.F.
        • Pouleur H.
        • Cocco G.
        • Wolff A.A.
        Comparative efficacy of ranolazine versus atenolol for chronic angina pectoris.
        Am J Cardiol. 2005; 95: 311-316
        • Stone P.H.
        • Gratsiansky N.A.
        • Blokhin A.
        • Huang I.Z.
        • Meng L.
        Antianginal efficacy of ranolazine when added to treatment with amlodipine: the ERICA (Efficacy of Ranolazine in Chronic Angina) trial.
        J Am Coll Cardiol. 2006; 48: 566-575
        • Morrow D.A.
        • Scirica B.M.
        • Karwatowska-Prokopczuk E.
        • et al.
        Effects of ranolazine on recurrent cardiovascular events in patients with non-ST-elevation acute coronary syndromes: the MERLIN-TIMI 36 randomized trial.
        JAMA. 2007; 297: 1775-1783
        • Wilson S.R.
        • Scirica B.M.
        • Braunwald E.
        • et al.
        Efficacy of ranolazine in patients with chronic angina observations from the randomized, double-blind, placebo-controlled MERLIN-TIMI (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Segment Elevation Acute Coronary Syndromes) 36 Trial.
        J Am Coll Cardiol. 2009; 53: 1510-1516
        • Morrow D.A.
        • Scirica B.M.
        • Chaitman B.R.
        • 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: 2032-2039
        • Kosiborod M.
        • Arnold S.V.
        • Spertus J.A.
        • et al.
        Evaluation of Ranolazine in Patients with Type 2 Diabetes Mellitus and Chronic Stable Angina. Results from the TERISA randomized clinical trial.
        J Am Coll Cardiol. 2013; 61: 2038-2045
        • Dhalla A.K.
        • Liu D.
        • Santikul M.
        • Belardinelli L.
        Ranolazine increases glucose-stimulated insulin secretion in-vitro and in-vivo.
        J Am Coll Cardiol. 2008; 51: A321
        • Gargiulo P.
        • Marciano C.
        • Savarese G.
        • et al.
        Endothelial dysfunction in type 2 diabetic patients with normal coronary arteries: A digital reactive hyperemia study.
        Int J Cardiol. 2013; 165: 67-71
        • Marciano C.
        • Galderisi M.
        • Gargiulo P.
        • et al.
        Effects of type 2 diabetes mellitus on coronary microvascular function and myocardial perfusion in patients without obstructive coronary artery disease.
        Eur J Nucl Med Mol Imaging. 2012; 39: 1199-1206