The Effects of Ranolazine on Hemoglobin A1c in a Veteran Population

Subjects were eligible for inclusion in this study if they were aged ≥ 18 years, had a diagnosis of type 2 DM, and received their first prescription of ranolazine at a VAMC from January 1, 2008 through March 31, 2015. Exclusion criteria included subjects with no baseline HbA_1c (defined as the HbA_1c result closest to the ranolazine initiation date and within 90 days before to 14 days after ranolazine initiation), no follow-up HbA_1c (defined as the first HbA_1c result within 60 to 180 days after the ranolazine initiation date), any change to their DM medication regimen during the follow-up period, or who discontinued ranolazine prior to collection of the follow-up HbA_1c.

Data were collected from the electronic health record (EHR) for each subject from 6 months prior to the ranolazine initiation date through 6 months after the ranolazine initiation date. The ranolazine initiation date was defined as the date ranolazine was picked up in person at a VAMC pharmacy or 7 days after the date filled for medications sent by mail. 

Progress notes, laboratory values, and pharmacy records were evaluated for this time frame, and the following data were collected: ranolazine dose and initiation date, ranolazine possession ratio (total numbers of days patient was in possession of ranolazine between initiation date and follow-up HbA_1c divided by total number of days between ranolazine initiation date and follow-up HbA_1c), baseline HbA_1c, follow-up HbA_1c, hypoglycemia incidence before and after the initiation of ranolazine, concomitant DM medications and interacting medications, patient age and sex, and creatinine clearance at baseline.

The primary endpoint of this study was the change in HbA_1c after ranolazine initiation. The secondary endpoint was the percentage of study subjects achieving HbA_1c < 7% and < 8% before and after the initiation of ranolazine.

To achieve 80% power to detect a change in HbA_1c of 0.4%, a sample size of 52 patients was required. For the primary endpoint, a paired t test was used to test for statistical significance. The McNemar test was used to evaluate for a significant change in subjects achieving an HbA_1c < 7% and HbA_1c < 8% with the initiation of ranolazine.

Results

A total of 523 patients were evaluated for study inclusion, of which 66 patients were included (Figure). The most common reasons for exclusion included no HbA_1c at baseline and changes to the DM medication regimen during follow-up. 

At baseline, the average age was 73.4 years, the patient population was 100% male, patients took an average of 1.3 antihyperglycemic agents at baseline, and the average HbA_1c was 6.9%. About 80% of patients were prescribed ranolazine at a dose of 500 mg twice daily (Table 1).

Ranolazine at any dose was associated with a change in HbA_1c of -0.3% (P < .001).

In addition, the percentage of veterans achieving HbA_1c < 7% was significantly higher after the initiation of ranolazine (P < .001). More veterans achieved HbA_1c < 8% after the initiation of ranolazine, although this result was not statistically significant (P = .22).

A dose of 500 mg ranolazine twice daily also was associated with a significant decrease in HbA_1c by 0.3% (P = .001). A significant increase in veterans achieving HbA_1c < 7% after ranolazine initiation was observed (42.3% before ranolazine initiation vs 73.1% after ranolazine initiation; P = .001), and a nonsignificant increase in veterans achieving HbA_1c < 8% was observed (82.7% before ranolazine initiation vs 90.4% after ranolazine initiation, P = .37).

At a dose of 1,000 mg twice daily, a 0.4% decrease in HbA_1c was observed. However, this result was not found to be statistically significant (P = .09), and the study was underpowered to detect a significant change in HbA_1c at this dose. 

A nonsignificant increase in veterans achieving HbA_1c < 7% was observed after ranolazine initiation (57.1% before ranolazine initiation vs 78.6% after ranolazine initiation, P = .25), but no difference was found in veterans achieving HbA_1c < 8%.

Hypoglycemia was not reported in a majority of study patient progress notes; thus, it was not evaluated further.

Discussion

In this study of a veteran population, ranolazine was associated with an HbA_1c decrease of 0.3%. This change is less than that observed in previous studies, which may be related to a lower baseline HbA_1c for the patients in this study. In addition, a greater percentage of veterans achieved an HbA_1c < 7% after initiation of ranolazine compared with that of the baseline.

To the authors’ knowledge, this is the first study evaluating ranolazine and HbA_1c in a veteran population. It also is the first study to demonstrate an association between HbA_1c lowering and ranolazine at a dose of 500 mg twice daily. These results suggest that in patients with chronic angina and type 2 DM, ranolazine could potentially play a dual role in therapy.