Clinical trial NCT01311323: Revascularization Strategies in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome (NSTE-ACS) and Severe Coronary Artery Disease
Official title: 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)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Multivessel Coronary Artery Disease
Acute Coronary Syndrome
Keywords: Multivessel Coronary Artery Disease
Left Main Narrowing
Percutaneous Coronary Intervention
Coronary Artery Bypass Grafting
Drug-Eluting Stent
Fractional Flow Reserve
Instant wave-free ratio
virtual Fractional Flow Reserve
Lead sponsor: American Heart of Poland
Sponsor class: OTHER
Collaborators: name: Andrzej Frycz Modrzewski Kraków University, Kraków, Poland
name: Upper Silesian Heart Center of Medical University of Silesia, Katowice, Poland
name: Silesian Centre for Heart Diseases
name: Clinical University Hospital, Białystok, Poland
First posted: 2011-03-09
Enrollment: 1000
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: Within last decade, aging of the population and coexistence of multiple comorbidities influenced a risk of patients presenting with acute coronary syndrome (ACS) 10,11. Furthermore, a steady decline in ST elevation ACS incidence and increase in non-ST elevation acute coronary syndrome (NSTE-ACS) has been observed 10,12,13, associated with poorer long term prognosis 14,15. This is related to the complexity of coronary artery disease in patients with NSTE-ACS, as nearly half of them have multivessel disease (MVD) 15. 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 16,17, 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 18. 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 7-9,19, 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 TeleDICOM 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.

Anticipated outcomes:

In the case of positive results of the study, the efficacy and safety of PCI in the studied group of patients will be confirmed. This will contribute to the creation of a new guidelines in a given area, translating into faster and easier access to rapid invasive treatment. It will also facilitate the decision-making process in centers without cardiac surgery.

Eligibility criteria: Inclusion Criteria:

* Acute Coronary Syndrome without ST elevation (NSTE-ACS): Unstable Angina (Braunwald's class IB,IC,IIB,IIC,IIIB,IIIC) or Non ST Elevation Myocardial Infarction (NSTEMI) requiring prompt revascularization (within 72 hours)
* Two vessel disease with proximal LAD stenosis or three vessel disease
* Unprotected Left Main Coronary Artery (ULMCA) de novo disease with or without concomitant single or multivessel coronary artery disease
* Syntax Score =\<33
* Patient eligible both for CABG and PCI, confirmed by interventional cardiologist and surgeon offering similar extension of revascularisation
* Signed informed consent

Exclusion Criteria:

* age \<21
* ST Elevation Myocardial Infarction;
* Stable angina;
* Patients in Killip IV class;
* Patients required immediate PCI procedure (e.g. electric instability);
* Patients unable to tolerate, obtain or comply with dual antiplatelet therapy for at least 1 year
* History of haemorrhagic stroke within a year before procedure
* Ischemic stroke or TIA within past 6 weeks.
* End Stage Chronic renal insufficiency requiring dialysis
* Concomitant structural or valve disease requiring cardiac surgery
* Prior PCI of left main trunk one year prior to randomization
* Prior PCI of any other coronary artery lesion within 1 year prior to randomization
* Prior CABG at any time prior to randomization
* Need for any concomitant cardiac surgery other than CABG (e.g. valve surgery, aortic repair, etc.), or intent that if the patient will be randomized to surgery, any cardiac surgical procedure other than isolated CABG will be performed
* Patients requiring additional surgery (cardiac or non cardiac) within 1 year
* 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

Primary outcomes:
measure: MACCE - Major Adverse Cardiac and Cerebral Events
timeFrame: One year after revascularization procedure
Secondary outcomes:
measure: SAE - Serious Adverse Events
timeFrame: peri-hospital period, one month and one year and two years after revascularization procedure
measure: Procedural and post procedural complication
timeFrame: peri-hospital period, one month and one year after revascularization procedure
measure: Overall costs of treatment strategies.
timeFrame: one year ofter revascularization procedure
measure: Occurence of stent thrombosis or graft occlusion
timeFrame: peri-hospital period, one month and one year after revascularization procedure
measure: Hemorrhagic complications.
timeFrame: peri-hospital period, one month and one year after revascularization procedure
measure: Frequency and impact of complete revascularization
timeFrame: one year after revascularization procedure
measure: LVEF
timeFrame: 6 and 12 months
Other outcomes:
Locations:
city: Chrzanow
country: Poland
facility: American Heart of Poland, Malopolska Centre for Heart and Vascular Disease
state: Malopolska
city: Bielsko-Biala
country: Poland
facility: American Heart of Poland, 2-nd Department of Cardiology
state: Silesia
city: Dabrowa Gornicza
country: Poland
facility: American Heart of Poland,3-rd Depatment of Invasive Cardiology, Angiology and Electrophysiology
state: Silesia
city: Ustron
country: Poland
facility: American Heart of Poland 1-st Department of Cardiology and Angiology
state: Silesia
city: Zabrze
country: Poland
facility: Silesian Centre for Heart Disease, Department of Cardiosurgery and Transplantation
state: Silesia
city: Białystok
country: Poland
facility: Clinical University Hospital
city: Katowice
country: Poland
facility: Upper Silesian Heart Center of Medical Univeristy of Silesia
Study officials:
affiliation: American Heart of Poland
name: Piotr P Buszman, MD,PhD, Assoc. Prof
role: PRINCIPAL_INVESTIGATOR
affiliation: American Heart of Poland
name: Andrzej Bochenek, Prof, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Buszman PE, Kiesz SR, Bochenek A, Peszek-Przybyla E, Szkrobka I, Debinski M, Bialkowska B, Dudek D, Gruszka A, Zurakowski A, Milewski K, Wilczynski M, Rzeszutko L, Buszman P, Szymszal J, Martin JL, Tendera M. Acute and late outcomes of unprotected left main stenting in comparison with surgical revascularization. J Am Coll Cardiol. 2008 Feb 5;51(5):538-45. doi: 10.1016/j.jacc.2007.09.054.
citation: Buszman PP, Bochenek A, Konkolewska M, Trela B, Kiesz RS, Wilczynski M, Cisowski M, Krejca M, Banasiewicz-Szkrobka I, Krol M, Kondys M, Wiernek S, Orlik B, Martin JL, Tendera M, Buszman PE. Early and long-term outcomes after surgical and percutaneous myocardial revascularization in patients with non-ST-elevation acute coronary syndromes and unprotected left main disease. J Invasive Cardiol. 2009 Nov;21(11):564-9.
citation: Buszman PE, Buszman PP, Kiesz RS, Bochenek A, Trela B, Konkolewska M, Wallace-Bradley D, Wilczynski M, Banasiewicz-Szkrobka I, Peszek-Przybyla E, Krol M, Kondys M, Milewski K, Wiernek S, Debinski M, Zurakowski A, Martin JL, Tendera M. Early and long-term results of unprotected left main coronary artery stenting: the LE MANS (Left Main Coronary Artery Stenting) registry. J Am Coll Cardiol. 2009 Oct 13;54(16):1500-11. doi: 10.1016/j.jacc.2009.07.007. Epub 2009 Aug 21.
citation: Park DW, Seung KB, Kim YH, Lee JY, Kim WJ, Kang SJ, Lee SW, Lee CW, Park SW, Yun SC, Gwon HC, Jeong MH, Jang YS, Kim HS, Kim PJ, Seong IW, Park HS, Ahn T, Chae IH, Tahk SJ, Chung WS, Park SJ. Long-term safety and efficacy of stenting versus coronary artery bypass grafting for unprotected left main coronary artery disease: 5-year results from the MAIN-COMPARE (Revascularization for Unprotected Left Main Coronary Artery Stenosis: Comparison of Percutaneous Coronary Angioplasty Versus Surgical Revascularization) registry. J Am Coll Cardiol. 2010 Jul 6;56(2):117-24. doi: 10.1016/j.jacc.2010.04.004. Epub 2010 May 6.
citation: Park DW, Kim YH, Yun SC, Lee JY, Kim WJ, Kang SJ, Lee SW, Lee CW, Kim JJ, Choo SJ, Chung CH, Lee JW, Park SW, Park SJ. Long-term outcomes after stenting versus coronary artery bypass grafting for unprotected left main coronary artery disease: 10-year results of bare-metal stents and 5-year results of drug-eluting stents from the ASAN-MAIN (ASAN Medical Center-Left MAIN Revascularization) Registry. J Am Coll Cardiol. 2010 Oct 19;56(17):1366-75. doi: 10.1016/j.jacc.2010.03.097.