Abstract 14196: A Pilot Randomized Trial of Intravenous Ivabradine vs Placebo on Top of Usual Care Following Percutaneous Coronary Intervention for ST-Segment-Elevation Myocardial Infarction
Background: heart rate (HR) is a major determinant of myocardial ischemia. Reducing HR in STEMI could limit infarct size and preserve left ventricular (LV) function. Ivabradine (IVA) is a pure HR reducing agent without effect on blood pressure or contractility. The safety and tolerability of IVA, particularly in intravenous form, in the context of STEMI is unknown. Aims and methods: this trial aimed to study the impact on HR of intravenous IVA (5 mg bolus, followed by 5 mg infusion over 8 hours, total dose 10 mg) in patients aged 40 to 80 years, diagnosed with STEMI ≤ 9 hours before study drug administration and treated with PCI < 6 h after symptom onset, in sinus rhythm with a baseline HR >80 bpm and systolic blood pressure >90 mm Hg. Other aims were to study the tolerability of IVA and its impact on LV function (by echocardiography with evaluation of the change from baseline in a subset of 18 patients) and infarct size (measured by CK and troponins and by MRI both prior to discharge and at 4 months in a subset of patients).
Results: 121 patients were randomized (81 IVA and 40 placebo (PLC)) and 40 enrolled in the MRI substudy. IVA produced a gradual and sustained HR reduction from 88.5 ± 9.5 bpm to 66.3 ± 10.2 bpm after 8 hours, compared to a change from 87.2 ± 8.1 bpm to 78.3 ± 14.6 in the PLC arm (p < 0.001). This was associated with a reduction in EDV and ESV (−19.6 ml and −15.5 ml, respectively) in the IVA arm compared to essentially no change in the PLC arm. Cardiac marker (CK-MB, Troponin I, Troponin T) release values were numerically lower with IVA compared to PLC. On MRI, the % of LV mass showing delayed hyperenhancement (DHE) before discharge was numerically smaller in the IVA arm vs PLC (12.9 ±10 vs 17.5 ± 11, NS). This trend was no longer present at 4 months. Bradycardia, leading to discontinuation of the treatment, was reported in 3 IVA treated patients.
Conclusions: Intravenous IVA produces a rapid and sustained HR reduction when used after PCI for STEMI. It is associated with trends towards lower levels of biochemical markers release, lower LV volumes at echocardiography and a smaller area of DHE on MRI. It was well tolerated and safe in this context. This suggests that intravenous ivabradine may be of potential value in STEMI and should be tested for its ability to improve outcomes.
- © 2010 by American Heart Association, Inc.