Effect of Ranolazine on A1C and Glucose Levels in Hyperglycemic Patients With Non-ST Elevation Acute Coronary Syndrome

OBJECTIVE We determined the relationships between glycemia at randomization, concurrent antidiabetic therapy, and change in A1C and fasting plasma glucose (FPG) in patients with diabetes receiving standard treatment for diabetes and randomized to ranolazine or placebo within the MERLIN-TIMI-36 (MERLIN) study. Ranolazine is a novel first-in-class drug approved for treating angina pectoris. RESEARCH DESIGN AND METHODS Randomization and 4-month glycemic and antidiabetes drug usage data from MERLIN were analyzed using Spotfire and SAS version 9.1 software. RESULTS In patients with diabetes and A1C of ≥8–10% at randomization (n = 171), there was an absolute A1C reduction in the ranolazine group of 1.2% (95% CI −1.4 to −1.0), and the placebo-adjusted (n = 182) decrease in A1C by ranolazine was 0.59% (95% CI −0.99 to −0.20, P < 0.001). In patients with FPG of 150–400 mg/dl at randomization, ranolazine (n = 131) compared with placebo (n = 147) reduced FPG by 25.7 mg/dl (95% CI −43.3 to −8.1, P = 0.001). When changes in either A1C or FPG were correlated to A1C or FPG at randomization, the slopes were significantly steeper for ranolazine than placebo (A1C, P = 0.046; FPG, P < 0.001), indicating that lowering of A1C and FPG by ranolazine is related to hyperglycemia at randomization. Ranolazine, compared with placebo, was not associated with serious hypoglycemic events, associated with significant changes in concurrent antidiabetic therapy, or dependent on a history of angina. CONCLUSIONS Ranolazine, when added to concurrent antidiabetes treatment, lowers FPG and A1C in patients with cardiovascular disease and poorly controlled diabetes.

[1]  E. Braunwald,et al.  Evaluation of the Glycometabolic Effects of Ranolazine in Patients With and Without Diabetes Mellitus in the MERLIN-TIMI 36 Randomized Controlled Trial , 2009, Circulation.

[2]  D. Nathan Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy: A Consensus Statement of the American Diabetes Association and the European Association for the Study of Diabetes , 2009, Diabetes Care.

[3]  Antonio Zaza,et al.  Pathophysiology and pharmacology of the cardiac "late sodium current.". , 2008, Pharmacology & therapeutics.

[4]  R. Kloner,et al.  Late sodium current inhibition as a new cardioprotective approach. , 2008, Journal of molecular and cellular cardiology.

[5]  D. Mozaffarian,et al.  Incidence of new-onset diabetes and impaired fasting glucose in patients with recent myocardial infarction and the effect of clinical and lifestyle risk factors , 2007, The Lancet.

[6]  D. Morrow,et al.  Ranolazine in patients with angina and coronary artery disease , 2007, Current cardiology reports.

[7]  A. Skene,et al.  Effects of ranolazine on recurrent cardiovascular events in patients with non-ST-elevation acute coronary syndromes: the MERLIN-TIMI 36 randomized trial. , 2007, JAMA.

[8]  C. Viscoli,et al.  Lower Baseline Glycemia Reduces Apparent Oral Agent Glucose-Lowering Efficacy , 2006, Diabetes Care.

[9]  J. Shryock,et al.  Inhibition of the late sodium current as a potential cardioprotective principle: effects of the late sodium current inhibitor ranolazine , 2006, Heart.

[10]  Peter Lindgren,et al.  Guidelines on diabetes, pre-diabetes, and cardiovascular diseases: executive summary , 2007 .

[11]  A. Skene,et al.  Evaluation of a novel anti-ischemic agent in acute coronary syndromes: design and rationale for the Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST-elevation acute coronary syndromes (MERLIN)-TIMI 36 trial. , 2006, American heart journal.

[12]  S. Raj,et al.  The Second Prevention of Syncope Trial (POST II)--a randomized clinical trial of fludrocortisone for the prevention of neurally mediated syncope: rationale and study design. , 2006, American heart journal.

[13]  J. Coresh,et al.  Glycemic control, atherosclerosis, and risk factors for cardiovascular disease in individuals with diabetes: the atherosclerosis risk in communities study. , 2005, Diabetes care.

[14]  H. Yagi,et al.  Glucose intolerance is common in Japanese patients with acute coronary syndrome who were not previously diagnosed with diabetes. , 2005, Diabetes care.

[15]  Neil R. Powe,et al.  Meta-Analysis: Glycosylated Hemoglobin and Cardiovascular Disease in Diabetes Mellitus , 2004, Annals of Internal Medicine.

[16]  B. Chaitman,et al.  Anti-ischemic effects and long-term survival during ranolazine monotherapy in patients with chronic severe angina. , 2004, Journal of the American College of Cardiology.

[17]  B. Chaitman,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. , 2004, JAMA.

[18]  J. Mckenney,et al.  National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) , 2002 .

[19]  A. Hamsten,et al.  Glucose metabolism in patients with acute myocardial infarction and no previous diagnosis of diabetes mellitus: a prospective study , 2002, The Lancet.

[20]  N. Unwin,et al.  Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Detection, Evaluation, and Treatment of High Blood Cholesterol Education Program (NCEP) Expert Panel on Executive Summary of the Third Report of the National , 2009 .

[21]  A. Tenenbaum,et al.  Non-insulin antidiabetic therapy in cardiac patients: current problems and future prospects. , 2008, Advances in cardiology.

[22]  A. Tenenbaum,et al.  Cardiovascular diabetology: clinical, metabolic and inflammatory facets. Preface. , 2008, Advances in cardiology.

[23]  B. Chaitman,et al.  Effects of ranolazine on exercise tolerance and HbA1c in patients with chronic angina and diabetes. , 2006, European heart journal.

[24]  S. Grundy,et al.  National Cholesterol Education Program Third Report of the National Cholesterol Education Program ( NCEP ) Expert Panel on Detection , Evaluation , and Treatment of High Blood Cholesterol in Adults ( Adult Treatment Panel III ) Final Report , 2022 .

[25]  P. Smits,et al.  Objectives Background Methods Results Conclusions , 2022 .