MedWire News: The anti-anginal drug ranolazine improves glycated hemoglobin (HbA1c) and recurrent ischemia in patients with diabetes mellitus, and reduces the incidence of increased HbA1c levels in those without previous evidence of hyperglycemia, according to research published in the journal Circulation.
Researchers prospectively evaluated the effect of ranolazine on HbA1c and clinical outcomes in the Metabolic Efficiency with Ranolazine for Less Ischemia in Non–ST-Elevation Acute Coronary Syndromes–Thrombolysis in Myocardial Infarction 36 (MERLIN-TIMI 36) trial, as an exploratory analysis had previously shown that the drug was associated with a significant reduction in HbA1c.
MERLIN-TIMI 36 randomly assigned 6560 patients with acute coronary syndrome to receive placebo or ranolazine initiated as an intravenous infusion and followed by oral administration at a dose of 1000 mg twice daily until the end of the study.
In this study, David Morrow (Brigham and Women’s Hospital and Harvard Medical School, Boston, MS, USA) and colleagues evaluated the 4918 patients from the MERLIN-TIMI 36 trial who had serial determinations of HbA1c at baseline and any subsequent time point.
The endpoint of worsening hyperglycemia was defined as an increase in HbA1c of at least 1%.
“Ranolazine significantly reduced HbA1c at 4 months compared with placebo (5.9% versus 6.2%),” report the researchers.
They note that this effect occurred despite the similar use of at least two antidiabetes agents in the ranolazine and placebo groups.
In patients with previously diagnosed diabetes, ranolazine-treated patients were more likely to achieve an HbA1c of 7% or less at 4 months compared with placebo (59% vs 49%) and were less likely to have an increase in HbA1c of 1% or more (14.2% vs 20.6% at 1 year).
An effect of ranolazine on HbA1c was also observed in those patients without a history of diabetes at baseline. The authors note that there was a small, but statistically significant decline in HbA1c in patients receiving ranolazine compared with a rise in HbA1c in those receiving placebo.
The study confirmed the anti-anginal effects of ranolazine without any increase in cardiovascular or other adverse events among patients with diabetes and high-risk coronary artery disease.
The authors acknowledge that additional studies specifically designed to assess the antidiabetes effects of ranolazine are needed to corroborate these findings and to determine the mechanism of action.
They conclude: “An effective anti-anginal that enhances the management of hyperglycemia, with established cardiovascular safety in a large outcomes trial, would be of particular appeal for the treatment of angina in the high-risk population with diabetes mellitus.”
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