SYNTAX study fails to support PCI as non-inferior to CABG in patients with left main or 3-vessel coronary artery disease

September 1, 2008 By Alexandra M. Palmer [mailto:apalmer@perfuse.org]

ESC 08-Munich, Germany: The SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery (SYNTAX) study failed to show that PCI is non inferior to CABG treatment in patients with left main or 3-vessel coronary artery disease. The findings were presented by Dr. Friedrich Mohr of Germany and Dr. Patrick Serruys of the Netherlands at the European Society of Cardiology Congress 2008 in Munich.

The goal of this trial was to compare the safety and efficacy of Taxus drug-eluting stents versus coronary artery bypass surgery (CABG) for the treatment of narrowed arteries in patients with complex coronary disease (blocked or narrowed arteries in both the right and left sides of the heart). The primary endpoint was non-inferiority of major adverse cardiac and cerebral events (MACCE) between the 2 groups at 1 year. MACCE is comprised of all cause death, cerebrovascular event (CVA/stroke), documented myocardial infarction, and repeat revascularization (PCI and/or CABG).

SYNTAX was a phase III, randomized, prospective, open label, parallel assignment, multicenter, multinational, safety/efficacy study which recruited patients from 62 sites in Europe and 23 sites in North America who presented with triple-vessel disease, left main disease or LM equivalent with or without 1-, 2- or 3-vessel disease (left anterior descending (LAD), left circumflex (LCx), right coronary artery (RCA) territory), de novo lesions with ≥50% stenosis, and myocardial ischemia (stable, unstable, silent). Patients who had undergone prior PCI or CABG, presented with acute myocardial infarction (with creatinine kinase >2x upper limit of normal), or had concomitant cardiac valve disease requiring surgical therapy (reconstruction or replacement) were excluded.

Patients amenable for both treatment options (n=1800, as decided by a surgeon and cardiologist) were randomized to receive either percutaneous coronary intervention (PCI) with polymer-based paclitaxel-eluting TAXUS stents (n=903, 28.2% diabetes mellitus (DM) patients) or to coronary artery bypass surgery (CABG, n=897, 28.5% DM patients). Patients amenable for only one treatment approach (n=1275) were allocated to one of two nested registries: PCI registry for CABG ineligible patients (n=198) or CABG registry for PCI ineligible patients (n=1077). The results discussed below pertain to the group of 1800 patients who were amenable for both CABG and PCI.

The duration of follow-up was 1 year, at which time there was a significantly higher rate of revascularization in the PCI group (13.7 vs. 5.9%, p<0.0001) and a significantly higher rate of CVA in the CABG group (2.2 vs. 0.6%, p=0.003). Overall MACCE was higher in the PCI group (17.8 vs. 12.1%, p=0.0015) due to an excess of redo revascularization compared with CABG. There was however no difference in the occurrence of all cause death, myocardial infarction and CVA among patients who underwent CABG and stenting (7.7% vs. 7.6%, p=0.98).

SYNTAX was a unique trial in that all-comers were invited to participate instead of a highly selected patient population. However, the study failed to support the non inferiority of PCI. The power of the trial is limited by the fact that the follow up time was only one year. Perhaps a longer follow up time will better differentiate between the roles of PCI and CABG as revascularization strategies and help stratify patients for the appropriate revascularization option.

Cardiologists wanting to put the results of the SYNTAX trial into everyday practice should take great care in doing so, according to cardiologist Duane Pinto. "I'd be cautious in generalizing the results of this study to all patients with multi-vessel disease," Dr. Pinto says. "If you break down the MACE (Major Adverse Cardiac Events) components, there may be a reason to change what you're doing. But there may not be." Pinto says cardiologists should carefully analyze the endpoints the investigators used in the study. "Is coming back to the cath lab for another procedure the same as having a stroke?"

SYNTAX was supported by Boston Scientific Corporation.

Reviewed by C. Michael Gibson, M.S., M.D.