Effect of Glucagon-like Peptide-1 Stimulation on Coronary Microvascular Dysfunction in Women With Angina Pectoris and no Obstructive Stenosis of Major Coronary Vessels
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 33
- 试验地点
- 1
- 主要终点
- Change from baseline in Angina Symptoms
研究概览
简要总结
The aim of the present study is to evaluate the effect of treatment with Liraglutide on the coronary microvasculature and angina symptoms, in overweight patients with microvascular dysfunction and angina pectoris but no coronary artery stenosis.
详细描述
Background:
Patients with symptoms and signs of ischemia are referred to coronary angiography (CAG) or CT angiography (CT-CAG). A significant proportion of these patients and especially women appear to have no obstructive coronary stenosis. Patients with angina-like symptoms and no macrovascular coronary stenosis have previously been considered without increased risk of major cardiovascular events, but novel data indicate that this assumption may not be true.
Abnormal coronary flow and metabolic response to stress have been reported, which is consistent with a possible microvascular ethology for the symptoms. Both endothelium- and non-endothelium dependent impaired coronary reactivity may contribute. The endothelium dependent component has been linked to risk factors and pro-inflammatory processes promoting atherosclerosis. The non-endothelium dependent mechanisms may involve vascular smooth muscle cells, undergoing alterations in phenotype in response to physiological and pathophysiological stimuli like hypertension and diabetes.
Both invasive and non-invasive diagnostic methods are available for the assessment of coronary microvascular dysfunction. In the absence of a flow limiting stenosis upstream, indirect measurement is possible by using transthoracic Doppler stress echocardiography (TTDSE). TTDSE provides assessment of coronary blood flow velocity in one of the major coronary vessels that can be used to determine coronary flow velocity reserve (CFR) after hyperemia. This method does primarily assess the non-endothelium dependent component of coronary microvascular dysfunction.
Despite reassurance that no stenosis on major coronary vessels is found, many patients continue to have chest pain resulting in emergency visits, hospitalizations and repeat cardiac catheterizations with adverse effect on quality of life, employment and health care costs.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 40 Years 至 75 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Women aged 40-75 with angina-like symptoms assessed by the Seattle Angina Questionnaire (SAQ).
- •Women aged 40-75 with angina-like symptoms assessed by the Seattle Angina Questionnaire (SAQ).
- •Referred for ischemic heart disease (IHD) assessment with no significant coronary stenosis (>50%) at coronary angiography or CT-angiography
- •Impaired CFR assessed by echo Doppler flow (defined ratio≤2,5).
- •BMI≥25kg/m2
排除标准
- •Allergy to dipyridamole, theophyllamine or liraglutide
- •Previous myocardial infarction or revascularization
- •No episodes of chest pain within 6 months before inclusion
- •Diabetes (reported, noted in journal or patient on antidiabetic medication)
- •Other causes of chest discomfort deemed highly likely
- •Left ventricular ejection fraction <45
- •Significant valvular disease
- •Congenital heart disease
- •severe co-morbidity with limited life-expectancy< 1 year
- •Severe asthma
- •Severe chronic obstructive pulmonary disease
- •Pregnancy (pregnancy test will be done at inclusion)
- •No use of contraception although in child-bearing age. A woman is regarded fertile, following menarche and until becoming post-menopausal unless permanently sterile. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. The birth control methods considered safe and effective includes combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device (IUD) and intrauterine hormone-releasing system ( IUS). Women in child-bearing age will have to use one of the above mentioned contraceptive methods from inclusion in the study until the end of study participation.
- •physical or mental disability
- •active cancer
- •significant renal (eGRF<30) or hepatic co-morbidity
- •chronic alcohol abuse
- •atrial fibrillation
- •Atrio-ventricular block>1st degree
- •chronic or previous acute pancreatitis
- •inflammatory bowel disease
- •history of thyroid carcinoma
- •participation in other clinical trial if relevant for the present study.
- •Language- or other barrier to giving informed consent
- •No signed informed consent
研究组 & 干预措施
Liraglutide
Liraglutide up to 3.0 mg daily injected subcutaneously (minimum 1.2 mg daily) for 12 weeks followed by 2 weeks of weight maintenance diet. Before initiating treatment participants will serve as their own controls for 4 weeks.
干预措施: Liraglutide (Drug)
结局指标
主要结局
Change from baseline in Angina Symptoms
时间窗: Assessed at baseline, week 4 and week 18
Assessed by the Seattle Angina Questionnaire
Change from baseline in Coronary Flow Reserve
时间窗: Assessed at baseline, week 4 and week 18
Assessed by transthoracic doppler stress echocardiography
次要结局
- Change in endothelial function(Assessed at baseline, week 4 and week 18)
- Change in body composition(Assessed before and after treatment (week 4 and week 18))
- Change in cardiac function(Assessed at baseline, week 4 and week 18)
- Change in body weight(Assessed at baseline, week 4 and week 18)
研究者
Eva Prescott
MD, DMSc
Bispebjerg Hospital