Multivessel and Left Main Coronary Artery Stenting in Comparison With Surgical Revascularization in Patients With Non ST Elevation Acute Coronary Syndrome. Prospective, Clinical Randomized Trial (The MILESTONE Trial)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 1,000
- 试验地点
- 10
- 主要终点
- MACCE - Major Adverse Cardiac and Cerebral Events
研究概览
简要总结
MILESTONE STUDY is dedicated to problems connected with patients with multivessel coronary artery disease and/or with left main narrowing who present symptoms of acute ischemia. For such kind of patients according to current ACC/AHA guidelines CABG (surgical revascularization) is recommended as a treatment method. In comparison with CABG, recent studies have shown that PCI (percutaneous coronary intervention) is associated with a lower rate of periprocedural adverse events and similar long term event-free survival in patients with left main disease. Our latest non randomized registry and randomized LEMANS study, comparing LMCA (left main coronary artery) stenting with CABG confirmed above findings. LEMANS ACS (acute coronary syndrome) retrospective registry of patients with UPLMCA (unprotected LMCA) disease and non ST elevation ACS showed lower 30 day and trend toward lower one year mortality after PCI when compared with CABG. It should be stressed, that acute ischemia substantially increase the risk of CABG. In fact, there are limited data on the outcome of ULMCA stenting or CABG in patients with acute coronary syndromes (ACS).
Similarly, all randomized studies comparing PCI vs CABG in multivessel disease included mainly patients with stable angina, small cohort of patients with unstable angina and they excluded patients with non ST elevation Myocardial infarction.
In the SYNTAX study -largest PCI vs CABG trial, randomized patients were patients with low perioperative risk (logistic EUROSCORE <5) and ACS patients routinely excluded. High perioperative risk patients were included only in PCI registry.
详细描述
Within last decade, aging of the population and coexistence of multiple comorbidities influenced a risk of patients presenting with acute coronary syndrome (ACS). Furthermore, a steady decline in ST elevation ACS incidence and increase in non-ST elevation acute coronary syndrome (NSTE-ACS) has been observed, associated with poorer long term prognosis. This is related to the complexity of coronary artery disease in patients with NSTE-ACS, as nearly half of them have multivessel disease (MVD). The optimal revascularization strategy in this group of patients remains unknown. Due to clinical presentation in most of cases early or delayed invasive strategy is preferred by both American and European guidelines, however the method of revascularization is not specified. Due to high surgical risk presentation, immediate stenting of the culprit lesion and delayed complete percutaneous revascularization is becoming a common practice. On the other hand, basing on the anatomical criteria coronary artery bypass grafting (CABG) should be the standard of care . Very few reports addressed so far the problem of optimal revascularization strategy in patients presenting with MVD and NSTE-ACS. A hypothesis of a positive outcome can be derived from some previous studies comparing PCI and CABG in which most of patients enrolled presented with NSTE-ACS, including our experience.
Aim and hypothesis:
Hence, the purpose of this study will be to compare contemporary coronary angioplasty with coronary artery bypass grafting in a prospective, clinical, multicenter, randomized trial. The hypothesis of this study is the non-inferiority of PCI compared to CABG in terms of the primary composite endpoint (death, myocardial infarction, stroke).
Method:
Patients with multivessel coronary artery disease, left main and acute coronary syndrome without ST segment elevation, qualified for early invasive treatment, with a Syntax Score below 33, and in whom the invasive cardiologist and cardiac surgeon will recognize both PCI and CABG as possible to achieve complete revascularization will be enrolled to the study. In the case of centers without the Cardiac Surgery Department, "Heart Team" consultations will take place via videoconference, and records of coronarography and echocardiography will be shared via the PACS (ang. Picture Archiving and Communication System system). The main exclusion criteria will be the qualification for conservative treatment, surgery other than CABG due to structural heart defect, ST segment elevation myocardial infarction, stable coronary artery disease, immediate need for PCI. After fulfilling the inclusion criteria and lack of exclusion criteria, the patient will be randomized in a 1: 1 ratio to either PCI or CABG. The PCI procedure will be performed after assessing the hemodynamic significance of all lesions with vFFR, FFR or iFR or using the latest generation drug eluting stents, and the implantation will be optimized based on intravascular imaging. CABG procedures will be performed based on the experience of the respective center, including the OPCAB technique, and the internal mammary artery will be used in each case. The primary endpoint of the study will be all cause death, myocardial infarction, and stroke in one-year follow-up. To prove the assumed hypothesis of the study, with the test power of 80% alpha error 5% and the percentage of lost to follow-up at the level of 5%, the study should include 500 patients in each group. Secondary endpoints will be ischemia driven revascularization, left ventricular ejection fraction, major and minor bleeding incidence, new onset of atrial fibrillation, de novo heart failure, unscheduled re-hospitalization, quality of life, and cost effectiveness. After the hospitalization, patients will be subjected to strict secondary prevention principles, including cardiac and cardiac surgery rehabilitation, and will undergo four specialistic follow-up visits with cardiac echo and stress tests at selected time points.
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
- •Subjects must meet ALL of the inclusion criteria to be considered for the trial. If ANY of the
排除标准
- •are met, the subject is excluded from the trial and cannot be randomized.
- •Age over 18 years,
- •Written patient consent,
- •Acute Coronary Syndrome without ST-segment elevation of high, intermediate and low risk, including NSTEMI and unstable angina requiring urgent (within 72 hours) invasive strategy,
- •Qualification for invasive treatment,
- •Multivessel coronary disease, defined as angiographic narrowing >50%DS on investigator's visual assessment in at least two major coronary artery territories (RCA, LAD, LCX), including involvement of the proximal segment of the left anterior descending artery or three-vessel disease with a Syntax Score <
- •Intermediate lesions (40-70%) will need to be assessed with either FFR, iFR, or VFFR). Patient may have left main coronary artery disease, defined as narrowing >50%DS (but this is not obligatory). For borderline changes, IVUS (MLA <6 mm2 or iFR=<0,90 or FFR=<0,80, with an anatomic Syntax Score <33 will be decisive,
- •Feasibility of complete revascularization on both the CABG and PCI sides,
- •Consent within the Heart Team for both CABG by the cardiothoracic surgeon and PCI by the interventional cardiologist.
- •Exclusion Criteria:
- •Age under 18 years,
- •ST-segment elevation myocardial infarction (STEMI) or new left bundle branch block (LBBB),
- •Stable coronary syndrome,
- •Single- or two-vessel coronary disease without involvement of the proximal LAD, defined as narrowing above 50%DS,
- •Qualification for conservative treatment,
- •Anticipated surgery other than CABG due to severe valvular defect or other structural defect, particularly moderate or severe mitral regurgitation,
- •Need for immediate coronary angioplasty treatment,
- •Syntax Score equal or above 33 (>=33),
- •Contraindications to short-term and long-term antiplatelet therapy,
- •Acute heart failure in class IV (cardiogenic shock),
- •Previous CABG procedure,
- •Previous PCI procedure within the last 6 months,
- •Ischemic or hemorrhagic stroke within 6 months prior to inclusion,
- •End-stage chronic kidney disease on dialysis,
- •Pregnancy or intention to become pregnant (women of child bearing age must have a recent negative pregnancy test prior to randomization),
- •Non cardiac co-morbidities with life expectancy less than 3 years,
- •Participation in other clinical trial that have not reached their primary endpoint.
研究组 & 干预措施
PCI with DES implantation
Percutaneous Coronary Intervention Implantation of Drug-Eluting Stents
干预措施: PCI (Procedure)
CABG
Coronary Artery Bypass Grafting.On-pump or Off-pump CABG
干预措施: CABG (Procedure)
结局指标
主要结局
MACCE - Major Adverse Cardiac and Cerebral Events
时间窗: One year after revascularization procedure
The primary endpoint is a composite of all cause death, spontaneous myocardial infarction, hospitalization due to heart failure or heart failure decompensation and stroke occurring within 12 months after PCI or CABG. The hypothesis test is designed to show non-inferiority of PCI to CABG for the primary endpoint
次要结局
- SAE - Serious Adverse Events(peri-hospital period, one month and one year and two years after revascularization procedure)
- Procedural and post procedural complication(peri-hospital period, one month and one year after revascularization procedure)
- Frequency and impact of complete revascularization(one year after revascularization procedure)
- Overall costs of treatment strategies.(one year ofter revascularization procedure)
- Occurence of stent thrombosis or graft occlusion(peri-hospital period, one month and one year after revascularization procedure)
- Hemorrhagic complications.(peri-hospital period, one month and one year after revascularization procedure)
- LVEF(6 and 12 months)
研究者
Piotr P Buszman, MD
M.D., PhD, Professor
American Heart of Poland