Can Ivabradine Attenuate Post-revascularisation Microcirculatory Dysfunction in Flow Limiting Coronary Artery Disease?
试验速览
- 阶段
- 4 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- IMR (Index of Microvascular Resistance)
研究概览
简要总结
The aim of the study is to test whether, in patients with angina and flow limiting epicardial coronary artery disease, pre-treatment with Ivabradine, as opposed to beta blockers, will reduce post percutaneous coronary intervention induced microvascular dysfunction.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Symptoms of Angina Pectoris
- •Angiographic evidence of epicardial coronary artery stenosis referred for PCI
- •Flow limiting lesion (Fractional Flow Reserve ≤0.80) in one of following locations (as defined in SYNTAX trial89):
- •Proximal or mid left anterior descending artery (LAD)
- •Proximal or mid dominant right coronary artery (RCA)
- •Proximal left circumflex artery (LCx) or 1ST Obtuse marginal Vessel
- •Existing beta blocker prescription
- •Echocardiogram performed within preceding 12 months
- •Patient consent
排除标准
- •Previous myocardial infarction (MI) in target vessel myocardial territory or any MI in preceding 12 months (defined by patient history, ECG changes and evidence of regional wall motion abnormalities on echocardiography)
- •FFR>0.80 in target vessel at time of procedure
- •Requirement for Multi-vessel intervention in a single procedure
- •Any chronic total occlusion (100% epicardial occlusion) on angiography
- •Distal coronary artery stenosis or that affecting non-dominant RCA
- •Heart Rate <60 bpm at inclusion (assessed by 12 lead ECG after minimum 10 minutes rest period)
- •Any rhythm other than sinus rhythm
- •Sick sinus syndrome or high grade atrio-ventricular block
- •Permanent Pacemaker in situ
- •Congenital QT Syndrome
- •Intolerance or allergy to beta-blockers
- •Intolerance to Ivabradine
- •Additional (other than angina pectoris) indication for beta-blocker treatment e.g. ventricular tachycardia
- •Concurrent required use of rate-limiting drugs other than beta-blockers
- •The necessity of combination therapy with Ivabradine and bisoprolol to achieve heart rate control
- •Contraindication to Magnetic Resonance Imaging or IV adenosine
- •Severe impairment of renal function (eGFR<30ml/min)
- •Severe Liver Disease (Any worse than Grade A by Child-Pugh Classification)
研究组 & 干预措施
Intervention
Patients randomised to stop beta blockers and start Ivabradine. Initial dose of 5mg BD, titrated to 7.5mg BD if possible.
干预措施: Ivabradine (Drug)
结局指标
主要结局
IMR (Index of Microvascular Resistance)
时间窗: Immediately after PCI
Invasive marker of microvascular dysfunction
次要结局
- Peri-procedural Troponin Release(3 hours after PCI)
- CFI pre-revascularisation(Immediately prior to PCI)
- Symptomatic Improvement (Seattle Angina Questionnaire)(18 weeks)
- Coronary Flow Reserve(12 weeks)