As percutaneous coronary intervention (PCI) continues to evolve, its ability to treat complex coronary artery disease (CAD) continues to improve.The SYNTAX (Synergy between PCI with Taxus and Cardiac Surgery) trial was designed to assess whether modern percutaneous techniques have assumed parity with coronary artery bypass surgery (CABG) for the treatment of complex (3 vessel or left main coronary disease) CAD.
This noninferiority, prospective, clinical trial enrolled 1800 patients over a two year period (March 2005-April 2007) from 85 sites in Europe and the United States. A ‘heart team’ consisting of an interventional cardiologist and a cardiac surgeon reviewed each subject’s data including coronary angiography after which a decision was reached on which procedure should be offered to a patient. Patients were treated with the aim of achieving complete revascularization of all vessels at least 1.5mm in diameter with stenosis of ≥50% as identified by the ‘heart team’. In patients who underwent PCI, antiplatelet medication was prescribed on the basis of directions of use for the TAXUS Express stent and local clinical practice. In most centres thienopyridines were continued after 6 months with 71.1% of patients receiving them at 1 year; aspirin was prescribed indefinitely for all patients. The primary clinical endpoint was a composite of major adverse cardiac and cerebrovascular events (MACCE): death from any cause, stroke, myocardial infarction or repeat revascularization throughout the 12 month period after randomization. The 12 month rates of MACCE were analyzed on the basis of the SYNTAX score.
Rates of MACCE at 12 months were significantly higher in the PCI group (17.8% vs 12.4% for CABG p = 0.002), predominantly driven by an increased rate of repeat revascularization with PCI (13.5% vs 5.9%, p < 0.001) and as a result the criterion for noninferiority was not met; but at 12 months the rates of the ‘hard’ endpoints – death and myocardial infarction – were similar between the two groups. Furthermore, stroke was significantly higher with CABG (2.2% vs 0.6% p = 0.003), although an imbalance in the subsequent medical management following the procedure meant that patients in the CABG arm had a lower rate of optimal medical therapy and this may have contributed to their higher risk of stroke.
There has been concern recently about the risk of late stent thrombosis with DES. In the SYNTAX trial the majority of cases of stent thrombosis occurred within 30 days of the procedure and the 12-month rate of stent thrombosis was similar to that of symptomatic graft occlusion in the CABG arm. However it should be noted that stent thrombosis usually has more severe consequences for patients (rate of death 30%, rate of MI >60%) than graft occlusion which usually manifests as angina leading to revascularization.
Some shortcomings need to be noted. The majority (78%) of the patients in the study were men and it is therefore unknown whether the findings are also applicable to women. The definition of MI used in the trial was based on a surgical definition (new Q waves on ECG in association with an increase in CKMB >5X the upper limit of the normal range) and may have resulted in less severe cases of MI being underreported.
For now patients with left main or 3 vessel disease should have their data reviewed by both a cardiologist and a cardiac surgeon to determine the likelihood of safe and effective revascularization by either method. If revascularization is feasible by both modalities then the SYNTAX score may help to identify the treatment with the optimal outcome. Irrespective of modality of revascularization, the importance of optimal medical therapy including antiplatelets, statins and ACE inhibitors must not be forgotten. Further trials, including the NHLBI sponsored FREEDOM trial and the UK based CARDia trial (comparing PCI and CABG in patients with diabetes), will add to the evidence base.
- Serruys PW, Morice MC, Kappetein P et al. Percutaneous Coronary Intervention versus Coronary Artery Bypass Grafting for Severe Coronary Artery Disease. N Engl J Med 2009; 360:961-72
- Lange RA and Hillis LD (ed). Coronary Revascularization in Context. N Engl J Med 2009;360:1024-5