A Multicentric Randomized Open Label Controlled Superiority Trial to Evaluate the Effectiveness of a Therapy With a Coronary Sinus Reducer as Compared to Guideline-directed Medical Therapy in Patients With Refractory Microvascular Angina
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 144
- 试验地点
- 2
- 主要终点
- Change in Canadian Cardiovascular Society angina class by two or more classes
研究概览
简要总结
Patients with refractory microvascular angina fulfilling the predefined inclusion and exclusion criteria will be enrolled in this randomized trial. The primary objective is to investigate whether the proportion of patients reporting an improvement in Canadian Cardiovascular Society (CCS) angina class (≥2 classes) is different at six months after implantation of a Coronary Sinus Reducer followed by optimal medical therapy (OMT) compared to OMT alone.
详细描述
Recent data show that 47% of the patients undergoing coronary angiography for angina have no epicardial disease. Of these, 52% have isolated microvascular angina, 17% have isolated vasospastic angina, 20% have both, and 11% have non-cardiac chest pain. These data suggest that microvascular disease is a highly prevalent condition, which might affect as many as 25% of all patients undergoing coronary angiography (without counting patients with acute coronary syndromes and those with mixed epicardial and microvascular disease). Based on an estimate of the Woman´s Ischemia Syndrome Evaluation (WISE) study, 3-4 million patients with symptoms of myocardial ischemia have non-obstructive coronary artery disease in the United States of America. These patients represent a significant burden in terms of mortality and morbidity as well as in terms of healthcare costs due to disability, hospitalization, and repeat testing.
Patients with microvascular angina require frequent hospitalizations, undergo repeat invasive procedures, have an impaired quality of life and a poor prognosis, since patients with a high index of microvascular resistances) have a higher risk of mortality (hazard ratio (HR) 1.6[0.8-3.4], P<0.001)). An analysis of the WISE study identified an impaired coronary flow reserve in the absence of epicardial disease as the strongest predictor of 5-year adverse events (26.7% versus 12.2%, HR 1.2[1.1.-1.4], P=0.008).
Although its importance is acknowledged by the most recent guidelines, microvascular angina represents a major clinical challenge. In particular, there is a strong disagreement on its classification, on the several mechanisms behind its pathophysiology, and the therapeutic alternatives available remain unsatisfactory.
Despite these uncertainties, there is a consensus that this condition is highly frequent, as it affects up to two-thirds of patients who suffer from stable angina and either have no coronary stenoses at angiography or have combined epicardial and microvascular disease.
The limits of medical therapy Traditional anti-ischaemic drugs are the first step in medical treatment, but their effectiveness is very limited in the setting of microvascular disease. Short-acting nitrates can be used to treat anginal attacks, but since nitrates are only effective on large arteries, this therapy is only indicated for the therapy of patients whose symptoms are caused by spasm of epicardial coronaries, and not for true microvascular angina. Beta-blockers limit myocardial oxygen consumption but do not affect the mechanisms of microvascular disease. Calcium antagonists, have shown variable results in clinical trials, but the limitation of this approach is that a significant heterogeneity exists in the types of calcium channels in the vasculature.
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
盲法说明
Given the nature of the intervention, there is not possibility to use a blinded design
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 and ≤85 years
- •Chronic coronary syndrome (including patients with anginal equivalents) refractory angina CCS class III-IV despite guideline-directed medical therapy
- •Evidence of reversible ischemia on non-invasive testing
- •Evidence of microvascular disease as diagnosed invasively by at least one of the following:
- •index of microvascular resistances (IMR) >25 and/or
- •coronary flow reserve (CFR) <2.0) with fractional flow reserve (FFR)>0.
- •Willingness to participate and ability to understand, read and sign the informed consent document before enrollment in the trial.
排除标准
- •Subjects presenting at least one of the following criteria will not be enrolled in the trial
- •Recent (within 3 months) acute coronary syndrome
- •Recent (within 6 months) revascularization by percutaneous coronary intervention (PCI, stent) or coronary artery by-pass surgery (CABG)
- •Recent (within 30 days) unsuccessful PCI
- •Decompensated congestive heart failure (CHF) or hospitalization due to CHF during the last 3 months
- •Left ventricular ejection fraction of <30%
- •Mean right atrial pressure >15mmHg
- •Anomalous or abnormal CS anatomy (e.g., tortuosity, aberrant branch, persistent left superior vena cava [SVC]) as demonstrated by angiogram
- •CS diameter at the site of planned Reducer implantation greater than 13mm or less than 9.5mm as measured by angiogram
- •Severe chronic obstructive pulmonary disease (COPD) indicated by a forced expiratory volume in one second that is less than 55 percent of the predicted value
- •Severe valvular heart disease
- •A pacemaker electrode in the coronary sinus
- •Tricuspid valve replacement or repair
- •Chronic renal failure (serum creatinine >2mg/dL), and/or on chronic hemodialysis
- •Moribund, or with comorbidities limiting life expectancy to less than one year
- •Known severe reaction to required procedural medications
- •Known allergy to stainless steel or nickel
- •Need for Magnetic Resonance Imaging (MRI) within 8 weeks after reducer implantation
- •Contraindication to dual antiplatelet therapy
- •Female of childbearing potential (last menstruation within the last 12 months or who did not undergo tubal ligation, ovariectomy or hysterectomy)
结局指标
主要结局
Change in Canadian Cardiovascular Society angina class by two or more classes
时间窗: 6 months
Proportion of patients improving ≥2 CCS angina classes at six months after the implantation followed byoptimal medical therapy (OMT) compared to OMT alone.
次要结局
- Change in angina severity according to the Seattle Angina Questionnaire(Six months)
- Procedural success(Implantation day)
- Number of unplanned hospitalizations for cardiac ischemia, angina or anginal equivalent, heart failure(6 months, 1 year, 5 years)
- Number of participants with technical success(Implantation day)
- Change in 5-level EQ-5D version (EQ-5D-5L)(6 months)
- Beck depression inventory(6 months)
- Frequency of use of sublingual nitrates (times per week)(6 months, 1 year, 5 years)
- Parameters of angina and quality of life(at 6 months)
- Number of documented Emergency Department (ED) visits due to angina episodes(6 and 12 months)
- Canadian Cardiovascular Society angina class(6 months, 1 year, 5 years)
- Incidence of adverse events(5 years)
研究者
Tommaso Gori
Clinical Professor
Johannes Gutenberg University Mainz