Ivabradine and Post-revascularisation Microcirculatory Dysfunction

We will be recruiting patients with stable angina referred for percutaneous intervention (PCI) due to flow limiting coronary artery disease. All patients will be on an existing beta blocker prescription (standard first line angina therapy). Our hypothesis is that Ivabradine will attenuate microvascular dysfunction post PCI when compared to standard beta-blocker pre-treatment. We intend to test this in a randomised, open-label parallel arm study with a direct comparison between Ivabradine and beta-blockers (standard therapy). Patients will be randomised to receive either Ivabradine (and stop beta blockers) or continue beta blockers for 6 weeks prior to the PCI procedure. The primary endpoint will be IMR (index of microvascular resistance) post PCI, as a marker of microvascular dysfunction and procedural related myocardial injury. IMR is a potent marker of adverse outcome in STEMI patients and in ACS after PCI. Although this has yet to be assessed in the elective setting, a reduction in IMR with Ivabradine may indicate a potential to improve outcomes and lessen iatrogenic microvascular dysfunction post PCI. IMR is assessed using thermodilution catheters placed distal to the coronary stenosis and by producing hyperaemia. To assess the medium term effects on the microcirculation post PCI all patients will have a stress perfusion cardiac MRI 12 weeks post procedure. The secondary endpoint will be proportion of patients with coronary flow reserve (CFR) <2.0 in PCI territory (regional myocardial blood flow at hyperaemia by intravenous adenosine infusion compared to rest). We will also be assessing CFI (collateral flow index), as promotion of the collateral system is one method by which Ivabradine may lessen procedural related myocardial injury, and ΔIMR as the difference between IMR pre and post-PCI.

The measurement of cardiac troponins and use of cardiac MRI will facilitate the identification of peri-procedural myocardial injury and procedural related myocardial infarction as further secondary end points. The Seattle Angina Questionnaire will be used at 3 intervals to assess symptoms throughout the study. The total study length for each patient will be 18 weeks.