Revascularization in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome (NSTE-ACS) With Multivessel and/or Unprotected Left Main Coronary Disease (MILESTONE)

• Composite of MACCE [ Time Frame: peri-hospital period, one month and one year after revascularization procedure ] [ Designated as safety issue: No ]
  MACCE is defined as: all death, myocardial infarction, stroke, or unplanned revascularization
• Procedural and post procedural complication [ Time Frame: peri-hospital period, one month and one year after revascularization procedure ] [ Designated as safety issue: No ]
  Procedural and post procedural complication: length of hospital stay and frequency of prolonged hospitalization ; return to work; readmissions and cause of readmissions; angina and functional status; medications.
• Overall costs of treatment strategies. [ Time Frame: one year ofter revascularization procedure ] [ Designated as safety issue: No ]
  Hospital costs and long-term cost-effectiveness.
• Occurence of stent thrombosis or graft occlusion [ Time Frame: peri-hospital period, one month and one year after revascularization procedure ] [ Designated as safety issue: No ]
  Stent trombosis will be defined in accordance with ARC definition.
• Hemorrhagic complications. [ Time Frame: peri-hospital period, one month and one year after revascularization procedure ] [ Designated as safety issue: No ]
  Hemorrhagic complications will be clasified according to TIMI scale.
• Frequency and impact of complete revascularization [ Time Frame: one year after revascularization procedure ] [ Designated as safety issue: No ]
  Complete revascularization will be defined on an anatomic basis and by revascularization of all significant ischemic areas.

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.

• Multi Vessel Coronary Artery Disease
• Acute Coronary Syndrome

• Procedure: PCI
  Percutaneous Coronary Intervention
  Other Names:

  • •Percutaneous coronary intervention
  • •Multivessel coronary disease
  • •Left main narrowing
• Procedure: CABG
  Coronary Artery Bypass Graft
  Other Names:

  • Multivessel coronary artery disease
  • Coronary artery bypass graft
  • Left Main narrowing

• Experimental: PCI with DES implantation
  Percutaneous Coronary Intervention Implantation of Drug-Eluting Stents
  Intervention: Procedure: PCI
• Active Comparator: CABG
  Coronary Artery Bypass Grafting.On-pump or Off-pump CABG
  Intervention: Procedure: CABG

• 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.
• Buszman PP, Bochenek A, Konkolewska M, Trela B, Kiesz RS, Wilczy?ski M, Cisowski M, Krejca M, Banasiewicz-Szkróbka 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.
• Buszman PE, Buszman PP, Kiesz RS, Bochenek A, Trela B, Konkolewska M, Wallace-Bradley D, Wilczy?ski M, Banasiewicz-Szkróbka I, Peszek-Przybyla E, Krol M, Kondys M, Milewski K, Wiernek S, Debi?ski 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. Epub 2009 Aug 21.
• 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. Epub 2010 May 6.
• 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.

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)
• 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
• 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
• Ischemic stroke or TIA within past 6 weeks.
• Hematocrit <30%
• Platelet Count <100.000/mm3
• Chronic renal insufficiency with creatinine clearance<30 ml/min/1,73m2,
• Concomitant structural or valve disease requiring cardiac surgery
• Prior PCI of left main trunk at any time 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