Evaluation of the Glycometabolic Effects of Ranolazine in Patients With and Without Diabetes Mellitus in the MERLIN-TIMI 36 Randomized Controlled Trial

David A. Morrow, Benjamin M. Scirica, Bernard R. Chaitman, Darren K McGuire, Sabina A. Murphy, Ewa Karwatowska Prokopczuk, Carolyn H. McCabe, Eugene Braunwald

Research output: Contribution to journalArticle

122 Scopus citations

Abstract

Background-Ranolazine is a novel antianginal shown in an exploratory analysis in patients with diabetes mellitus and chronic angina to be associated with a decline in hemoglobin A1c(HbA1c). We designed a prospective evaluation of the effect of ranolazine on hyperglycemia as part of a randomized, double-blind, placebo-controlled outcomes trial.Methods and Results-We compared HbA1c(percentage) and the time to onset of a >1% increase in HbA1camong 4918 patients with acute coronary syndrome randomized to ranolazine or placebo in the MERLIN-TIMI 36 trial. Ranolazine significantly reduced HbA1cat 4 months compared with placebo (5.9% versus 6.2%; change from baseline, -0.30 versus -0.04; P<0.001). In patients with diabetes mellitus treated with ranolazine, HbA1cdeclined from 7.5 to 6.9 (change from baseline, -0.64; P<0.001). Diabetic patients were more likely to achieve an HbA1c<7% at 4 months with ranolazine compared with placebo (59% versus 49%; P<0.001) and were less likely to have a >1% increase in HbA1c(14.2% versus 20.6% at 1 year; hazard ratio, 0.63; 95% confidence interval, 0.51 to 0.77; P<0.001). Moreover, ranolazine reduced recurrent ischemia in diabetic patients (hazard ratio, 0.75; 95% confidence interval, 0.61 to 0.93; P=0.008). Notably, in patients without diabetes mellitus at baseline, the incidence of new fasting glucose >110 mg/dL or HbA1c>6% was reduced by ranolazine (31.8% versus 41.2%; hazard ratio, 0.68; 95% confidence interval, 0.53 to 0.88; P=0.003). Reported hypoglycemia did not increase with ranolazine (P=NS).Conclusions-Ranolazine significantly improved HbA1cand recurrent ischemia in patients with diabetes mellitus and reduced the incidence of increased HbA1cin those without evidence of previous hyperglycemia. The mechanism of this effect is under investigation. (Circulation. 2009;119:2032-2039.)

Original languageEnglish (US)
Pages (from-to)2032-2039
Number of pages8
JournalCirculation
Volume119
Issue number15
DOIs
StatePublished - Apr 21 2009

Keywords

  • Angina
  • Coronary disease
  • Diabetes mellitus
  • Hemoglobin A1c

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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