Effect of Ranolazine on A1C and Glucose Levels in Hyperglycemic Patients With Non-ST Elevation Acute Coronary Syndrome
- Jeffrey W. Chisholm, PHD1,
- Allison B. Goldfine, MD2,
- Arvinder K. Dhalla, PHD1,
- Eugene Braunwald, MD3,
- David A. Morrow, MD, MPH3,
- Ewa Karwatowska-Prokopczuk, MD1 and
- Luiz Belardinelli, MD4
- 1Division of Cardiovascular Therapeutics, Gilead Sciences, Palo Alto, California;
- 2Joslin Diabetes Center, Boston, Massachusetts;
- 3TIMI Study Group, Brigham and Women's Hospital and Department of Medicine, Boston, Massachusetts;
- 4Division of Cardiovascular Therapeutics, Gilead Sciences, Foster City, California.
- Corresponding author: Jeffrey W. Chisholm, jeff.chisholm{at}gilead.com.
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J.W.C. and A.B.G. contributed equally to this work.
Abstract
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.
Footnotes
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Clinical trial reg. no. NCT00099788, clinicaltrials.gov.
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
- Received December 21, 2009.
- Accepted March 9, 2010.
- © 2010 by the American Diabetes Association.
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
