D. Morrow, B. Scirica, B. Chaitman
Apr 21, 2009
Citations
5
Influential Citations
144
Citations
Quality indicators
Journal
Circulation
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 HbA1c among 4918 patients with acute coronary syndrome randomized to ranolazine or placebo in the MERLIN-TIMI 36 trial. Ranolazine significantly reduced HbA1c at 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, HbA1c declined 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 HbA1c and recurrent ischemia in patients with diabetes mellitus and reduced the incidence of increased HbA1c in those without evidence of previous hyperglycemia. The mechanism of this effect is under investigation.