This article is more than 5 years old. Information may no longer be current.
Ranolazine may be most effective in uncontrolled diabetes among patients with PCI, incomplete revascularization
Click Here to Manage Email Alerts
At 6 months, ranolazine decreased HbA1c and improved angina frequency in patients with uncontrolled diabetes who underwent incomplete revascularization with PCI, according to a substudy of the RIVER-PCI trial.
Of the 2,604 patients with chronic angina and incomplete revascularization after PCI who were randomly assigned to ranolazine (Ranexa, Gilead Sciences) or placebo, 961 (36.9%) had diabetes. Among these patients, 87.4% had type 2 diabetes, 3.4% had type 1 diabetes, and the rest had HbA1c levels of at least 6.5%.
Impact on glucose
Among all patients, ranolazine, compared with placebo, was associated with mean reductions in HbA1c of 0.28% at 6 months and 0.29% at 12 months. Among patients with diabetes vs. those without diabetes, mean reductions with ranolazine were also greater at 6 months (0.42% vs. 0.19%) and 12 months (0.44% vs. 0.2%; P < .001 for interaction at both time points).
Moreover, the researchers found a lower incidence of new-onset diabetes among patients treated with ranolazine vs. placebo at 6 months (OR = 0.49; 95% CI, 0.25-0.93) but not 12 months (OR = 0.59; 95% CI, 0.32-1.06). They were also less likely than those treated with placebo to have an increase in HbA1c of at least 1% at 6 months (30.2% vs. 52.9%; OR = 0.39; 95% CI, 0.33-0.47) and at 12 months (29.1% vs. 51.8%; OR = 0.38; 95% CI, 0.31-0.46). These results were comparable for patients with and without diabetes.
Regardless of assigned treatment, patients with diabetes experienced reduction in angina frequency, as measured by the Seattle Angina Questionnaire (SAQ) score. A greater proportion of patients treated with ranolazine, compared with placebo, also experienced resolution of angina (53.3% vs. 49.6%) at 6 months, and among patients with diabetes, the ranolazine group had better SAQ scores than the placebo group at 6 months (88.3 vs. 85.4; P = .033) but not at 12 months (88.2 vs. 86.6; P = .18).
In patients with an HbA1c of 7.5% or greater at baseline, ranolazine vs. placebo was associated with less angina and better SAQ score at 6 months (89.7 vs. 83.9; P = .008) but not at 12 months. Reduction in angina frequency was also numerically greater among these patients than those with HbA1c lower than 7.5% (P for interaction = .07), the researchers noted.
Among patients with diabetes, 30.6% discontinued ranolazine, and discontinuation was more common among those treated with ranolazine, compared with placebo, at 6 and 12 months. The rate of discontinuation was also higher among patients with HbA1c of at least 7.5% than among those with HbA1c lower than 7.5% (40.2% vs. 30.9%) at 12 months.
“Future studies are needed to confirm the interaction between the antianginal effects of ranolazine and glucose control and elucidate potential mechanisms,” the researchers wrote.
Certain patients benefit
In an accompanying editorial, Peter H. Stone, MD, of Brigham and Women’s Hospital and Harvard Medical School, wrote ranolazine may be particularly effective in a specific patient population.
“Ranolazine remains effective, as well as guideline-supported, for the treatment of stable angina,” Stone wrote. “However, these recurrent observations that the greatest therapeutic effect from ranolazine may occur in the context of the most severe hemodynamic and metabolic stress suggest opportunities to focus this treatment strategy on those patients who have a more compromised underlying pathophysiological substrate and who may thereby most benefit from the protective effects of blocking late Na+ influx.” – by Melissa Foster
Disclosure: Gilead Sciences sponsored the RIVER-PCI trial. Please see the full study for a list of the researchers’ relevant financial disclosures. Stone reports no relevant financial disclosures.
Click Here to Manage Email Alerts