Abstract 2453: Effect of Ranolazine on Hemoglobin A1c in the MERLIN-TIMI 36 Randomized Controlled Trial
Ranolazine is a novel anti-anginal shown to be associated with a reduction in hemoglobin A1c (HbA1c) in exploratory analyses in patients (pts) with diabetes mellitus (DM) & chronic angina. We designed a prospective evaluation of the effect of ranolazine on HbA1c as part of a randomized, double-blind, placebo-controlled trial in ACS.
METHODS: We compared HbA1c (%) and the time to onset of worsening hyperglycemia (>1% increase in HbA1c) in pts with non-ST elevation ACS randomized to ranolazine or placebo in the MERLIN-TIMI 36 Trial. HbA1c data are reported as least-square means.
RESULTS: Among 4306 pts with serial data, ranolazine significantly reduced HbA1c at 4 mo compared with placebo (5.9% vs 6.2%, Δ from baseline -0.30 vs -0.04, p=0.001). In pts with DM treated with ranolazine, HbA1c declined from 7.5 to 6.8 (Δ-0.64, p<0.001, Fig⇓). As such, pts with DM were more likely to achieve a HbA1c <7% at 4 mo when treated with ranolazine vs placebo (59% vs. 49%, p<0.001). In addition, worsening of hyperglycemia by 1 yr of follow-up was less likely in DM pts treated with ranolazine (14.2% vs 20.6%; HR 0.63; 95% CI 0.51, 0.77, p<0.001). Notably, in pts without DM at baseline (fasting glucose <100mg/dL & HbA1c<6%), the incidence of new fasting glucose <110 mg/dL or HbA1c ≥6% was also reduced by ranolazine (31.8% vs. 41.2%; HR 0.68; 95% CI 0.53, 0.88; p=0.003). Reported hypoglycemia in pts with DM was similar between treatment groups (3% vs 3%).
CONCLUSIONS: In this prospective validation, ranolazine significantly improved HbA1c in pts with DM and reduced the incidence of newly increased HbA1c in those without evidence of previous hyperglycemia. The mechanism of this effect is under investigation.