Ffr-gUidance for compLete Non-cuLprit REVASCularization - a Registry-based Randomized Clinical Trial
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 1,542
- 试验地点
- 2
- 主要终点
- Combined endpoint of all-cause mortality, or myocardial infarction, or unplanned revascularization.
研究概览
简要总结
Background: The best strategy for ST-elevation myocardial infarction (STEMI) patients with multi-vessel disease, who undergo primary percutaneous coronary intervention (PCI) of the infarct-related artery (IRA) in the acute phase with remaining multivessel disease, is still not well established. Current guidelines recommend PCI of only the infarct related artery (IRA). However, recent small scale randomised controlled trials indicate that full revascularization of these non-infarct related arteries during the index procedure is superior to initial conservative treatment. Fractional flow reserve (FFR), a method used to determine ischemia-inducing lesions, has been shown to be superior to angiography-guided PCI in stable angina.
Objective and methods: To test the hypothesis that a strategy of systematic complete revascularization with FFR-guided PCI following STEMI/very high risk NSTEMI leads to improved clinical outcomes compared to initial conservative management of non-culprit lesions. The trial is a prospective international multicentre registry-based randomized controlled trial with combined primary endpoint of all-cause mortality, or non-fatal MI, or unplanned revascularization at a minimum follow-up of 2-3 years. The first key secondary endpoint is the combined endpoint of all-cause mortality or myocardial infarction. The second key secondary endpoint is unplanned revascularization. 1542 patients with acute STEMI/very high risk NSTEMI with multi-vessel disease in Sweden, Denmark, Serbia, Finland, Latvia, Australia and New Zealand will be randomized into 2 arms:
- FFR-guided PCI of non-culprit lesions during index hospital admission or
- Initial conservative management following acute PCI of the culprit lesion(s) or
Randomization and data collection in the registries - the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) and corresponding registries in other countries (or electronic data capture) - will ensure low bias, high inclusion rate and excellent follow-up of events at a low cost. Adjudication of clinical events and collection of data from other registries including death cause registries is also planned.
Significance: If this study shows that FFR-guided PCI of non-culprit lesions in STEMI/very high risk NSTEMI improves clinical outcome compared to conventional management this will change practise in how we should best manage these patients. Therefore a study of this size will definitely be of great importance in determining future guidelines for this large patient group to reduce both morbidity and mortality.
详细描述
Background Information: Early epicardial coronary reperfusion is a prerequisite for the effective salvage of ischemic myocardium and reduces morbidity and mortality in patients with ST elevation myocardial infarction (STEMI). The recent ESC guidelines currently recommend percutaneous coronary intervention (PCI) of only the infarct related artery (IRA) in the setting of acute ST-elevation myocardial infarction (STEMI). Subsequent management of residual disease is initially conservative with a low threshold for non-invasive investigation for residual ischemia. There is a recent meta-analysis of 34279 patients with 1819 cardiovascular deaths registered during follow-up showing that PCI of the culprit lesion only is associated with reduced mortality as compared to full revascularization at the time of STEMI in multivessel disease. Also in non ST-segment elevation myocardial infarction (NSTEMI), the strategy of multivessel PCI for suitable significant stenoses-rather than PCI limited to the culprit lesion-has not been evaluated in an appropriate, randomized fashion according to the European Society of Cardiology guidelines on myocardial revascularization. In NSTEMI there is growing evidence to suggest a benefit of an invasive strategy within 2 h in patients with a very high risk profile according to the ESC NSTEMI guidelines. Accordingly, also patients with a very high risk NSTEMI requiring urgent revascularization may be included in the current study.
Recent small scale randomised controlled trials (RCT) have however produced results which suggest that in cases where there is anatomically significant non-culprit multi-vessel disease full revascularization of these non-infarct related arteries during the index procedure or at least during the same hospitalization is superior to initial conservative treatment. Since these studies were so small and also go against earlier observational studies and current guidelines it is therefore difficult to draw any conclusions on how to treat this patient group in the optimal way to reduce mortality.
By way of paradox, in recent years it has been shown that fractional flow reserve (FFR) used to determine ischemia-inducing lesions is superior to angiography guided PCI in both stable angina and in NSTEMI. Whether performing full revascularization of physiologically significant non-culprit lesions for patients with STEMI improves outcome compared to an initial conservative approach is not known. The primary PCI in multivessel disease study(PRIMULTI) was a small study (650 patients) that investigated this question with a combined primary endpoint of all cause death, myocardial infarction or revascularization at one year. In PRIMULTI conservative treatment was safe; there was no difference at all regarding death and myocardial infarction, only revascularization. One critique of these studies is that they are including revascularization in the primary endpoint and it is expected that you will increase revascularization if you leave significant stenoses untreated. The key question is if complete revascularization prevents death or MI.
Therefore, the aim of this study is to investigate whether in patients with STEMI/rescue PCI/risk evaluation following successful thrombolysis/very high risk NSTEMI FFR-guided PCI of non-culprit lesions during the index hospital admission will improve cardiovascular outcomes compared to an initially conservative approach of non-culprit lesions. The study aim is powered statistically for the combined primary endpoint of total mortality and myocardial infarction (MI) at a minimum follow-up of 1 year (all events when the last patient has been for 1 year).
Assessments and Procedures:
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
- •The following specific criteria must be fulfilled:
- •Symptoms indicating acute myocardial ischemia with a duration >30 min and occurring ≤ 24 h prior to randomization or presentation.
- •One of the following:
- •STEMI: ST elevation above the J-point of ≥0.1 millivolt in ≥ two contiguous leads or left bundle branch block
- •Risk evaluation following successful thrombolysis
- •Very high risk NSTEMI: dynamic ECG changes or ongoing chest pain or acute heart failure or hemodynamic instability independent of ECG changes or life-threatening ventricular arrhythmias.
- •PCI performed of infarct-related artery.
- •One or more non-culprit lesions at least 2.5 mm on angiogram (visually assessed as 50-99%) amenable for PCI.
- •Age >18 years.
- •Ability to provide informed consent.
排除标准
- •Previous CABG.
- •Left main disease of >50% stenosis requiring intervention.
- •Cardiogenic shock necessitating therapy in addition to revascularization. (LV support device or vasopressors).
研究组 & 干预措施
FFR Treatment Arm
Following PCI of the infarct related artery it is up to the PCI operator to perform FFR-guided PCI of non-infarct related lesion(s) during the index procedure or later during the index hospital admission. For stenosis grade 90-99% FFR is not mandatory (but recommended). An FFR value of ≤0.80 is to be considered significant for ischemia with a recommendation that non-culprit PCI is performed. It is up to the operator to decide whether to use intra-venous or intracoronary adenosine during FFR. An FFR of >0.80 is to be considered non-significant for ischemia with a recommendation that medical management is pursued.
Pressure wires: Only Fractional Flow Reserve pressure wires from St Jude Medical or Boston Scientific can be used in this study.
干预措施: FFR Treatment Arm (Procedure)
Conservative Treatment Arm
Only the infarct-related artery will be treated with PCI in this treatment arm during the index hospital admission. Medical therapy for angina pectoris is at the investigators discretion. Clinical follow-up of symptoms is recommended, but it is also acceptable to make a plan at hospital discharge for a later outpatient non-invasive stress-test. It is not acceptable to plan for an elective PCI in this treatment arm without signs of ischemia or symptoms.
干预措施: Conservative Treatment Arm (Other)
结局指标
主要结局
Combined endpoint of all-cause mortality, or myocardial infarction, or unplanned revascularization.
时间窗: Minimum 2-3 years
Combined endpoint of all-cause mortality, or myocardial infarction, or unplanned revascularization during a minimum follow-up of 2-3 years.
次要结局
- Combined end point of all-cause mortality, MI, and unplanned revascularization (PCI/CABG) at a minimum follow-up of 2-3 years in pre-specified subgroups(Minimum 2-3 years.)
- Cardiovascular mortality(Minimum 2-3 years.)
- Number of patients with unplanned revascularization (PCI/CABG) of the coronary arteries(Minimum 2-3 years.)
- Any revascularization (PCI/CABG)(Minimum 2-3 years.)
- Rehospitalization due to heart failure(Minimum 2-3 years.)
- Health Economic evaluation of direct and indirect costs during follow-up(Minimum 2-3 years.)
- All-cause mortality(Minimum 2-3 years.)
- Length of index hospital stay(1 month)
- Quality of life according to the questionnaire EQ-5D at nurse visit at two months and/or one year for those patients that are registered in SEPHIA (Sweden only).(Minimum 2-3 years.)
- Combined endpoint of all-cause mortality, or myocardial infarction.(Minimum 2-3 years.)
- Myocardial infarction (fatal and non-fatal)(Minimum 2-3 years.)
- Stent thrombosis (all treated vessels including nonculprit vessels)(Minimum 2-3 years.)
- Instent restenosis (all treated vessels including nonculprit vessels)(Minimum 2-3 years.)
- Target vessel revascularization (all treated vessels including nonculprit vessels)(Minimum 2-3 years.)
- Angina pectoris according the Seattle Angina Questionnaire-7 (SAQ-7)(Minimum 2-3 years.)
研究者
Felix Bohm
MD, PhD, Interventional Cardiologist
Karolinska University Hospital