Abstract 14751: Effectiveness of Ranolazine in Patients With Type 2 Diabetes Mellitus and Chronic Stable Angina According to Baseline Hemoglobin A1c
Background: In the TERISA trial, ranolazine reduced the frequency of angina and the use of sublingual nitroglycerin (SL NTG) in patients with type 2 diabetes (T2DM) and stable angina. Because pre-clinical data suggest that late sodium current (INaL) is greater in cardiomyocytes exposed to high glucose, we sought to investigate whether ranolazine (an inhibitor of INaL) has greater therapeutic effectiveness among TERISA patients with poor glycemic control.
Methods: TERISA was a multinational, randomized, double-blind trial of ranolazine vs placebo in patients with T2DM, CAD, and stable angina. Anginal episodes and SL NTG use were recorded daily in an electronic diary. Health status was evaluated at baseline and 8 weeks post-randomization using the Seattle Angina Questionnaire (SAQ). The interaction between baseline HbA1c and treatment effect was tested across endpoints using ANCOVA models, with HbA1c as a continuous variable with restricted cubic splines. For endpoints with significant interaction terms, the effectiveness of ranolazine vs placebo was plotted against HbA1c.
Results: Overall, 949 patients with mean HbA1c of 7.3% were randomized. The interaction of HbA1c and treatment was significant for the primary endpoint of angina frequency (p=0.027), the key secondary endpoint of SL NTG use (p=0.031), SAQ angina frequency (p=0.001), and SAQ treatment satisfaction (p=0.025). For these endpoints, there was a continuous relationship between greater therapeutic effectiveness of ranolazine and higher HbA1c values, with the benefit of the drug more pronounced when HbA1c levels were above ~6.5% (Figure).
Conclusion: Among patients with T2DM, CAD, and stable angina, the therapeutic benefits of ranolazine in terms of angina frequency, SL NTG use and health status were greater in those with higher HbA1c values. These data suggest that ranolazine should be particularly beneficial to patients with suboptimal glycemic control.
- © 2013 by American Heart Association, Inc.