Abstract
Background
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.
Methods
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.
Results
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.
Conclusions
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.
Keywords
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 accessOne-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:
Subscribe to International Journal of CardiologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Angina 1 year after percutaneous coronary intervention: a report from the NHLBI Dynamic Registry.Am Heart J. 2002; 144: 826-833
- Effect of PCI on quality of life in patients with stable coronary disease.N Engl J Med. 2008; 359: 677-687
- 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
- Economic impact of angina after an acute coronary syndrome: insights from the MERLIN-TIMI 36 trial.Circ Cardiovasc Qual Outcomes. 2009; 2: 344-353
- 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
- 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
- Optimal medical therapy with or without PCI for stable coronary disease.N Engl J Med. 2007; 356: 1503-1516
- Ranolazine for the treatment of chronic angina and potential use in other cardiovascular conditions.Circulation. 2006; 113: 2462-2472
- Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.J Clin Epidemiol. 2009; 62: 1006-1012
- Incorporating variations in the quality of individual randomized trials into meta-analysis.J Clin Epidemiol. 1992; 45: 255-265
- 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
- Calcium channel blockers and cardiovascular outcomes: a meta-analysis of 175,634 patients.J Hypertens. 2009; 27: 1136-1151
- 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 www.cochrane-handbook.org)])
- Meta-analysis.STB Rep. 1998; 7: 100-109
- 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 www.cochrane-handbook.org])
- Assessing the influence of a single study in meta-analysis.STB. 1999; 47: 15-17
- Meta-analysis regression.STB. 1998; 42: 16-22
- Explaining heterogeneity in meta-analysis: a comparison of methods.Stat Med. 1999; 18: 2693-2708
- Bias in metaanalysis detected by a simple, graphical test.BMJ. 1997; 315: 629-634
- Anti-ischemic effects and long-term survival during ranolazine monotherapy in patients with chronic severe angina.J Am Coll Cardiol. 2004; 43: 1375-1382
- 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
- Effects of ranolazine on exercise tolerance and HbA1c in patients with chronic angina and diabetes.Eur Heart J. 2006; 27: 42-48
- Comparative efficacy of ranolazine versus atenolol for chronic angina pectoris.Am J Cardiol. 2005; 95: 311-316
- 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
- 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
- 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
- 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
- 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
- Ranolazine increases glucose-stimulated insulin secretion in-vitro and in-vivo.J Am Coll Cardiol. 2008; 51: A321
- Endothelial dysfunction in type 2 diabetic patients with normal coronary arteries: A digital reactive hyperemia study.Int J Cardiol. 2013; 165: 67-71
- 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
Article info
Publication history
Published online: September 23, 2013
Accepted:
August 30,
2013
Received:
July 25,
2013
Identification
Copyright
© 2013 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.