PCI vs. CABG in Patients With Three-Vessel or LM CAD: Who Finally Won the Battle of the Titans?

The SYNTAXES study (Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery Extended Survival) is the 10-year follow-up of the original SYNTAX trial. It is the study with the longest follow-up comparing coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) with drug-eluting stents (DES) in the treatment of three-vessel or left main (LM) coronary artery disease (CAD).

The SYNTAX trial was initially published in 2009,1 and it remains the landmark study for decision-making and risk stratification of complex CAD. Both the initial trial with 1-year follow-up and the numerous sub-studies within the 5-year follow-up have been published with a primary outcome of a composite of major adverse cardiac and cerebrovascular events.2-4 In all of these studies, CABG demonstrated fewer major adverse cardiac and cerebrovascular events compared with PCI. Arguably most importantly, the SYNTAX study introduced the heart team concept and the SYNTAX score to allow assimilation and grading of the patients' coronary disease burden.

In 2018, 5-year data from the SYNTAX trial and other similar randomised studies (11 randomised trials involving 11,518 patients) comparing PCI with CABG for complex CAD were assembled and meta-analyzed.5 All-cause mortality was significantly higher with PCI compared with CABG. Due to the large number of individual data, subgroup analysis was feasible. It showed that in non-diabetic patients with multivessel disease and low (≤22) SYNTAX score, PCI was as safe and effective as CABG. Similarly, patients with non-complex LM disease had similar survival with PCI and CABG. In diabetic patients, a trend for better outcome with CABG compared with PCI was observed as the SYNTAX score increased. Conclusions from this meta-analysis were adopted from the European Society of Cardiology Revascularization Guidelines, and recommendations were made accordingly.6

These changes in recommendations led to a debate between cardiologists and cardiac surgeons7-9 that was highlighted in the accompanying editorial of the SYNTAXES trial.10 The main reason for debate was the lack of long-term follow-up in comparative PCI/CABG trials. Publication of the SYNTAXES trial attempts to fill this gap, providing long-term follow-up data on mortality of patients in the SYNTAX trial with a median follow-up duration of 11.2 years.

The primary outcome of SYNTAXES was all-cause death at 10 years in patients previously assigned to PCI with DES versus CABG. The secondary outcome was all-cause death at maximum available follow-up. According to the authors, the primary outcome in SYNTAXES occurred in 27% of the PCI patients and in 24% of the CABG patients (hazard ratio [HR] 1.17; 95% confidence interval [CI], 0.97-1.41; p = 0.092), concluding that there is no significant difference between the 2 treatments.11 Furthermore, these results were consistent across the 2 different lustrums (0-5 and 5-10 years). However, superiority of CABG compared with PCI was observed for the secondary endpoint, with PCI increasing the risk of death by 18% compared with CABG.

A more detailed investigation showed that patients with three-vessel disease had a survival advantage with CABG versus PCI at 10 years (21% vs. 28% died, respectively; HR 1.41; 95% CI, 1.10-1.80; p = 0.006). In three-vessel disease, high SYNTAX score (>33) was the principal differentiator. Contrary to previous reports in SYNTAX or similar studies in diabetics,12 diabetes was not a differentiator of prognosis. No difference between the 2 groups was evident in patients with LM disease (26% vs. 28%, respectively; HR 0.90; 95% CI, 0.68-1.20; p = 0.47).

SYNTAXES is the longest study to date to follow patients treated with first-generation DES and compare outcomes with CABG. Moreover, despite the long duration of follow-up, 94% of the patients had a complete follow-up. However, the results of the study have to be considered and applied to practice. Disappointingly, the primary endpoint of major adverse cardiac and cerebrovascular events used in previous SYNTAX trial reports was not available due to the design of this study. Thus, any speculation on the exact cause of the deaths reported within SYNTAXES is not possible.13 Indeed, due to the formal end of the original SYNTAX trial, any data after the 5 years of follow-up on contemporary medical treatment, invasive treatment, or possible cross-over are lacking. Additionally, these data do not reflect contemporary practice, including use of first-generation DES that are known to have higher repeat revascularisation and stent thrombosis rates,14 incomplete revascularisation in many patients, no intracoronary imaging, and a lack of physiological guidance for strategy (Figure 1). Many of these limitations have been addressed in the SYNTAX II trial.15 In this study, patients were selected using an evolution of the SYNTAX score—the SYNTAX II score—that combined the angiographic score with some clinical characteristics. Revascularisation was based on pressure wire assessment, a third-generation stent was used, and the result was analysed and optimized using intravascular ultrasound. Better complete revascularisation rates were achieved using contemporary techniques for chronic occlusions, and, finally, improved, more potent antithrombotic agents were available. These newer dual antiplatelet therapy (DAPT) regimes have been shown to improve results after PCI in extensive CAD.16 Encouragingly, initial data from SYNTAX II shows significantly better results than the PCI arm in SYNTAX and data comparable to the surgical arm at 2-year follow-up.17

Figure 1

Figure 1
Timeline of achievements that improve or may improve outcome in PCI and CABG during the years of follow-up for the SYNTAXES trial in parallel with the incidence of death at 1, 3, 5, 10, and 12.9 years post-randomisation based on published data. ART, Arterial Revascularization Trial; BIMA, bilateral internal mammary artery; CORONARY, CABG Off or On Pump Revascularization Study; DAPT 2014, Dual Antiplatelet Therapy; DAPT, dual antiplatelet therapy; DEFINE-FLAIR, Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation; FAME, Fractional Flow Reserve Versus Angiography for Multivessel Evaluation; FFR, fractional flow reserve; iFR, instantaneous wave-free ratio; ILLUMIEN III: OPTIMIZE PCI: Optical Coherence Tomography Compared to Intravascular Ultrasound and Angiography to Guide Coronary Stent Implantation: a Multicenter Randomized Trial in Percutaneous Coronary Intervention; IVUS, intravascular ultrasound; OCT, optical coherence tomography; PLATO, Platelet Inhibition and Patient Outcomes; POL-MIDES, Prospective Randomised Pilot Study Evaluating the Safety and Efficacy of Hybrid Revascularization in Multivessel Coronary Artery Disease; RADIAL, Radial Artery Database International Alliance; SPIRIT IV, A Clinical Evaluation of the XIENCE V® Everolimus Eluting Coronary Stent System in the Treatment of Patients With de Novo Native Coronary Artery Lesions; SWEDEHEART, Swedish Web-system for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies; TRITON, Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel

In our opinion, results of the SYNTAXES trial provide useful information on outcomes after revascularization in complex CAD. CABG provided better (more complete) revascularisation then and, unsurprisingly, better long-term survival compared with PCI. In 2019, we must prioritise complete revascularisation and abolition of ischaemia, and this requires more than an angiographically based procedural algorithm. Use of comparative risk score informs the heart team decisions, and availability of contemporary guideline-directed PCI techniques will facilitate better outcomes. Notably, mortality rates are suboptimal in SYNTAXES even in the CABG patients, and improved drug therapy to modify prognosis is required, especially in patients with diabetes.


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  16. Kotsia A, Brilakis ES, Held C, et al. Extent of coronary artery disease and outcomes after ticagrelor administration in patients with an acute coronary syndrome: Insights from the PLATelet inhibition and patient Outcomes (PLATO) trial. Am Heart J 2014;168:68-75.e2.
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Clinical Topics: Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Stable Ischemic Heart Disease, Atherosclerotic Disease (CAD/PAD), Aortic Surgery, Cardiac Surgery and SIHD, Interventions and Coronary Artery Disease, Interventions and Imaging, Angiography, Echocardiography/Ultrasound, Nuclear Imaging, Chronic Angina

Keywords: Coronary Artery Disease, Drug-Eluting Stents, Percutaneous Coronary Intervention, Platelet Aggregation Inhibitors, Fibrinolytic Agents, Taxus, Prospective Studies, Tomography, Optical Coherence, Mammary Arteries, Confidence Intervals, Constriction, Pathologic, Follow-Up Studies, Fractional Flow Reserve, Myocardial, Radial Artery, Coronary Artery Bypass, Heart Diseases, Diabetes Mellitus, Angiography, Coronary Angiography, Prognosis, Thrombosis, Treatment Outcome, Algorithms, Risk Assessment, Ultrasonography, Interventional, Evidence-Based Medicine, Angina, Stable

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