Ranolazine, a sodium channel blocker, significantly improved angina in patients with diabetes and coronary artery disease (CAD), a randomised, double-blind trial has found.

A total of 949 diabetes patients with CAD were randomised to treatment with ranolazine or placebo, in the TERISA trial. All had a high burden of angina with six or seven episodes per week and were receiving one or two antianginal drugs (beta blockers, calcium channel blockers and long-acting nitrates).

The mean age of the participants was 64 years, 61% were men, mean diabetes duration was 7.5 years, and mean baseline HbA1c 7.3%. Patients were recruited across 104 centres in 14 countries.

After a single-blind, four-week placebo run-in, patients were randomised to eight weeks of ranolazine, target dose 1,000 mg bid or placebo. Episodes of angina and sublingual GTN use were recorded daily in an electronic diary.

The primary outcome was the average weekly number of episodes of angina over the last six weeks of the study.

Frequency of angina was significantly lower with ranolazine compared with placebo, 3.8 episodes per week (95% CI: 3.6-4.1) and 4.3 episodes per week (95% CI:4.0-4.5, P = 0.008) respectively.

GTN use was also significantly reduced in the ranolazine group, 1.7 doses per week (95% CI:1.6-1.9) compared with 2.1 doses per week in the placebo group (95% CI:1.9-2.3, P = 0.003). There was no difference in the incidence of serious adverse events between groups.

There have been some new additions to the antianginal drug formulary over the past few years and the sodium channel blocker ranolazine has been one such drug.

Quite often the more novel and expensive newer drugs are relegated down the pick list behind well established choices such as beta blockers, long-acting nitrates and calcium antagonists.

However, this trial has identified a potential niche for ranolazine in the management of diabetes patients with stable angina. Such patients often have more extensive CAD and limited options for revascularisation compared with those without diabetes, and a high burden of angina.

The authors conclude that ranolazine is effective in treating angina in this high-risk group and is well tolerated.

Furthermore, they point to a subgroup analysis which showed a greater benefit in patients with a higher HbA_1c and suggest that further trials are required to investigate this as well as the notion that ranolazine may improve glycaemic control.

This was a small trial over a relatively short period and the absolute effects were small but it should certainly act as a prompt for more detailed investigation.

Dr Peter Savill

• Kosiborod M, Arnold SV, Spertus JA et al. Evaluation of ranolazine in patients with type 2 diabetes mellitus and chronic stable angina: Results from the TERISA randomized clinical trial. J Am Coll Cardiol 2013; doi:10.1016