TY - JOUR
T1 - Evaluation of the Glycometabolic Effects of Ranolazine in Patients With and Without Diabetes Mellitus in the MERLIN-TIMI 36 Randomized Controlled Trial
AU - Morrow, David A.
AU - Scirica, Benjamin M.
AU - Chaitman, Bernard R.
AU - McGuire, Darren K
AU - Murphy, Sabina A.
AU - Prokopczuk, Ewa Karwatowska
AU - McCabe, Carolyn H.
AU - Braunwald, Eugene
PY - 2009/4/21
Y1 - 2009/4/21
N2 - 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.)
AB - 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.)
KW - Angina
KW - Coronary disease
KW - Diabetes mellitus
KW - Hemoglobin A1c
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U2 - 10.1161/CIRCULATIONAHA.107.763912
DO - 10.1161/CIRCULATIONAHA.107.763912
M3 - Article
C2 - 19349325
AN - SCOPUS:65449149816
SN - 0009-7322
VL - 119
SP - 2032
EP - 2039
JO - Circulation
JF - Circulation
IS - 15
ER -