Effects of ranolazine on exercise tolerance and angina frequency in patients with severe chronic angina receiving maximally-tolerated background therapy: analysis from the Combination Assessment of Ranolazine In Stable Angina (CARISA) randomized trial

Background: Ranolazine has been previously shown to improve exercise capacity and symptoms in patients with severe chronic angina treated with standard doses of beta-blockers and calcium-channel blockers, without a significant effect on heart rate or blood pressure. Objective: The purpose of this study was to assess whether the benefit of ranolazine extends to the subgroup of angina patients treated with maximally-tolerated doses of beta-blockers or calcium blockers. Methods and results: In this post-hoc analysis, 258 patients from the Combination Assessment of Ranolazine In Stable Angina (CARISA) trial were considered as treated with maximally-tolerated doses of beta-blockers or calcium-channel blockers (systolic blood pressure (SBP) <= 100 mm Hg, and/or a resting heart rate <= 60 beats per minute, and/or an ECG PR interval >= 200 msec). Change from baseline in total exercise duration after 12 weeks compared to placebo were 34.5 (95% CI 0.8; 68.1) sec (p = 0.045) with ranolazine (750/1000 mg bid) at trough drug levels and 46.3 (13.5; 79.1) (p = 0.006) at peak drug levels. The number of angina attacks per week compared to baseline were reduced compared to placebo (-2.3 +/- 0.3 vs -0.9 +/- 0.6 (p < 0.001)). The effects of ranolazine 750 mg bid and 1000 mg bid were similar and the beneficial effects of ranolazine in this subgroup of maximally-treated patients were consistent with those not on maximally-tolerated doses of the background therapy. Conclusion: Ranolazine is effective for the symptomatic treatment of patients with stable angina on background therapy with maximally-tolerated doses of first line anti-anginal therapies.