A Developmental Clinical Study of Management Guided by Coronary Angiography Combined With Fractional Flow Reserve (FFR) Measurement Versus Management Guided by Coronary Angiography Alone(Standard Care) in Patients With Non-ST Elevation MI.
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 350
- 试验地点
- 12
- 主要终点
- The between-group difference in the proportion of patients allocated to medical management compared to revascularization.
研究概览
简要总结
Background: In patients with acute non-ST elevation myocardial infarction (NSTEMI) coronary arteriography is usually recommended however visual interpretation of the coronary angiogram is subjective. A complementary diagnostic approach involves measuring the pressure drop across a coronary stenosis (fractional flow reserve, FFR) with a pressure-sensitive guidewire.
Hypothesis: Routine FFR measurement is feasible in NSTEMI patients and has additive diagnostic, clinical and health economic utility, as compared to angiography-guided standard care.
Design: A prospective multi-center randomized controlled trial in 350 NSTEMI patients with ≥1 coronary stenosis ≥30% severity (threshold for FFR measurement). Patients will be randomized immediately after coronary angiography to the FFR-guided group or angiography-guided group (FFR measured, not disclosed). All patients will then undergo FFR measurement in all vessels with a coronary stenosis ≥30% severity. FFR will be measured in culprit and non-culprit lesions in all patients. FFR will be disclosed to guide treatment in the FFR guided-group but not disclosed in the 'angiography-guided' group. In the FFR-guided group, an FFR>0.80 will be an indication for medical therapy whereas an FFR≤0.80 will be an indication for revascularization by percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG), as appropriate. The primary endpoint is the between-group difference in the proportion of patients allocated to medical management compared to revascularization. A key secondary composite outcome is the occurrence of cardiac death or hospitalization for myocardial infarction or heart failure. Other secondary outcomes include quality of life, hospitalization for unstable angina, coronary revascularization or stroke, and healthcare costs. Exploratory analyses will also assess the relationships between FFR and angiographic lesion characteristics (severity, culprit status). The minimum and average follow-up periods for the primary analysis are 6 and 18 months respectively. A secondary analysis with longer term follow-up (minimum 3 years) is planned. Screen failures who gave informed consent will be entered into a registry.
Importance: Our developmental clinical trial will address the feasibility of FFR measurement in NSTEMI and the influence of FFR disclosure on treatment decisions and health and economic outcomes.
详细描述
Background
Acute non-ST elevation myocardial infarction (NSTEMI) is the commonest form of acute coronary syndrome (ACS) and a leading global cause of premature morbidity and mortality. A coronary angiogram is recommended in intermediate-high risk NSTEMI patients to detect obstructive coronary artery disease (CAD) and so identify patients who may benefit from coronary revascularization. In ACS patients, stress testing before invasive management is not recommended and so functional information on ischemia is usually not available. Therefore, usual care is based on visual interpretation of coronary disease severity revealed by the angiogram and treatment decisions include medical therapy, percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG). Since visual assessment of the angiogram may be inaccurate, judgements made by cardiologists in every day practice are subjective, potentially leading to misdiagnosis and incorrect treatment decisions.
Recent studies (DEFER, FAME, FAME II) in patients with stable coronary artery disease (CAD) have presented a new approach to the diagnostic management of CAD. Fractional flow reserve (FFR) is an index of the physiological significance of a coronary stenosis and is defined as the ratio of maximal blood flow in a stenotic artery to normal maximal flow. An FFR ≤0.80 is an evidence-based physiological threshold that correlates with the presence of inducible ischemia on non-invasive testing. Alternatively, an FFR >0.80 indicates that patients can be managed safely with medical therapy. DEFER and FAME highlighted the benefits of FFR measurement in stable CAD to more accurately identify flow-limiting stenoses and guide PCI leading to improved outcomes and reduced costs compared to angiography alone. In FAME 2, compared to optimal medical therapy alone, PCI combined with optimal medical therapy reduced the likelihood of urgent revascularization in patients with stable symptoms and functionally significant coronary disease. Overall, FFR measurement can identify and exclude obstructive coronary artery disease with high diagnostic accuracy, including in patients with prior MI.
FFR measurement in unstable coronary artery disease
There is some uncertainty over the validity of FFR when measured in patients with recent MI. FFR measurement requires maximal coronary hyperemia which theoretically may be less readily achieved in patients with recent MI, potentially, because of microvascular injury.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Blinding of FFR result
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
- •NSTEMI with an elevated troponin (> upper limit of normal for local reference range) with at least one CAD risk factor (e.g. diabetes, age > 65 years, prior CAD, prior peripheral vascular disease, hypertension, hyperlipidaemia, family history of CAD).
- •At least one coronary lesion ≥ 30% stenosis severity.
- •Invasive management scheduled within 10 days of admission and ideally performed within 72 h of admission or a history of recurrent ischemic symptoms within 5 days.
排除标准
- •On-going ischemic symptoms (i.e. chest pain) not controlled by medical therapy.
- •Cardiogenic shock or hemodynamic instability.
- •Angiographic exclusion: highly tortuous or calcified arteries, left main stenosis >80% angiographically (i.e. consistent with severe left main disease).
- •Life expectancy of < 1 year.
- •MI with persistent ST elevation.
- •Intolerance to anti-platelet drugs.
- •Unsuitable for either PCI or CABG on clinical or angiographic grounds.
- •Coronary artery disease < 30% reference vessel diameter.
- •Absence of a non-flow limiting coronary stenosis ≥30%.
- •Non-coronary cardiac surgery (e.g. concomitant valve repair or replacement).
- •Inability to give informed consent.
- •Age < 18 years (no upper age limit).
结局指标
主要结局
The between-group difference in the proportion of patients allocated to medical management compared to revascularization.
时间窗: Baseline: the treatment decision will be made by the clinical team in the cardiac catheter laboratory during the index procedure or shortly afterwards during the index hospitalization when a multidisciplinary heart team review is indicated.
The between-group difference in the proportion of patients allocated to medical management compared to coronary revascularization by percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG).
次要结局
- The safety and feasibility of routine FFR measurement in patients with recent NSTEMI.(Post randomization index procedure at baseline.)
- Major adverse cardiac events are defined as cardiac death or hospitalization for myocardial infarction (MI) or heart failure.(Post-randomization (any time including the index procedure through follow-up), expected average follow-up of 18 months (minimum follow-up 6 months).)
- The % rate of discordance between an FFR <= or >0.80 and coronary stenosis severity (stenosis > or <70% of reference vessel diameter (50% for left main) assessed visually).(Baseline: Visual assessment of the angiogram before randomization, index procedure)
- Health economics(Post-randomization (including the index procedure through longer term mean follow-up of 18 months (minimum follow-up 6 months).)
- Quality of life(Baseline through longer term follow-up (average follow-up 18 months, minimum follow-up 6 months))
研究者
Colin Berry
Professor Colin Berry
NHS National Waiting Times Centre Board