Abstract 1799: Ranolazine Reduces Ischemia as Detected on Continuous ECG (Holter) in Patients with non-ST-Elevation ACS in the MERLIN - TIMI 36 Trial
Background: Recurrent ischemia after admission for non-STE ACS is common and associated with poor outcomes. In patients with chronic CAD, ranolazine, a novel antianginal agent, improves symptoms and delays the time until ST depression during stress tests without any effect on HR or BP. Continuous ECG (CECG) monitoring is a sensitive marker of recurrent ischemia.
Methods: 6560 pts admitted with NSTEACS were randomized to ranolazine or placebo in the MERLIN-TIMI 36 trial. At randomization, 6355 pts (99%) had 3-lead CECG monitoring initiated (median duration 6.9 days). The primary CECG endpoint was the rate of ST dep ≥1mm from baseline lasting ≥ 1 min with heart rate at onset <100 bpm. Exploratory analyses using ST dep ≥ 0.5mm were also performed.
Results: Ranolazine did not reduce the rate of the primary CECG endpoint compared to placebo (19.2 v. 20.5%, RR 0.93, p=0.18) through the entire 7 day recording period though it did reduce events >72hrs after randomization (11.6 v. 13.6%, RR 0.86, p=0.02). When using the lower ischemic threshold of 0.5 mm, however, ranolazine did reduce ischemic episodes (22.9 v. 25.1, RR 0.91, p=0.039). This effect was consistent regardless of HR at the onset of ischemia, but the reduction appeared more prominent with elevated HR (Figure⇓).
Conclusion: Ranolazine, a novel antianginal agent, appears to reduce the rate of ischemia as detected by CECG in pts with NSTEACS using a more sensitive ECG cutpoint for ischemia, in particular several days after randomization and episodes that start with an increased HR. This suggests that the greatest antianginal effect of ranolazine may be to diminish “demand-related” ischemia