Multivessel PCI on its 40th anniversary: finally a match for CABG?

In 2017 we celebrate the 40th anniversary of percutaneous coronary intervention (PCI), first performed by Andreas Gruentzig on 16 September 1977. Recognizing the limitations of percutaneous transluminal coronary balloon angioplasty (PTCA), including high rates of acute closure and restenosis, Gruentzig initially believed his technique was best reserved for patients with single-vessel coronary artery disease (CAD). Yet a number of pioneers expanded the use of PTCA to complex CAD, forecasting its superiority to coronary artery bypass graft (CABG) surgery in multivessel disease (MVD). However, early randomized trials demonstrated suboptimal outcomes of PTCA compared with CABG, especially in diabetic patients with MVD. These differences have narrowed in the last two decades, first with the introduction of bare metal stents, then with drug-eluting stents (DES). The most renowned study to probe the boundaries of PCI is the SYNTAX trial, in which 1800 patients with three-vessel or left main (LM) CAD were randomized between 2005 and 2007 to CABG vs. PCI with first-generation paclitaxel-eluting stents (PES). Surprisingly, LM patients had relatively better outcomes with PCI than those with three-vessel disease. In the latter subgroup (n = 1095), the primary endpoint of major adverse cardiac and cerebrovascular events [MACCE; death, myocardial infarction (MI), stroke, or revascularization] at 1 year occurred in 19.2% vs. 11.5% of patients after PCI vs. CABG, respectively (P < 0.001), and in 37.5% vs. 24.2%, respectively (P < 0.001), at 5 years. Thus, CABG remained the preferred revascularization modality for most patients with complex MVD. One of the greatest legacies of the SYNTAX trial is the creation of the anatomic SYNTAX score (SS). Three-vessel disease patients with low CAD complexity (SS <_ 22) in SYNTAX had similar 5-year MACCE rates with PCI and CABG, whereas those with intermediate or high CAD complexity (SS >_ 23) had superior outcomes with surgery. Notwithstanding issues in reproducibility and training, the SS has stood the test of time and has been incorporated into EU and US guidelines. The SYNTAX score II (SSII) was subsequently developed to discriminate further the outcomes of PCI vs. CABG by adding clinical variables to the anatomic SS. As elegantly described, the SSII identifies some patients with a low SS for whom CABG might be preferred, and others with a higher SS in whom PCI might be preferred, at least as regards prediction of 4-year mortality. However, after applying the SSII in the SYNTAX trial, equipoise was still present in 59% of threevessel disease patients in whom 4-year mortality could not be projected to differ between PCI and CABG with 95% certainty. In the decade since the SYNTAX trial, PCI has substantially evolved (Figure 1). The introduction of second-generation DES has markedly improved both the safety and efficacy of PCI, especially by reducing stent thrombosis, which was responsible for a substantial proportion of adverse events after PES in SYNTAX. Randomized trials have demonstrated that physiological lesion assessment can identify non-flowlimiting lesions which do not require intervention, thereby reducing stent use and MACCE. Stent optimization with intravascular ultrasound (IVUS) imaging guidance improves event-free survival, even with DES. Specialized techniques and devices to recanalize chronic total occlusions (CTOs) allow experts to achieve 90% success rates. The potent P2Y12 platelet receptor antagonists prasugrel, ticagrelor, and cangrelor reduce MI and stent thrombosis after PCI in acute coronary syndromes. Bleeding avoidance strategies, including radial artery intervention and bivalirudin, have become increasingly utilized. A large-scale network meta-analysis has suggested that PCI in the contemporary DES era may have eliminated the incremental advantage of CABG over PCI in reducing death and MI compared with medical therapy alone in stable CAD. Finally, the fundamental importance of optimal medical therapy after revascularization has also been increasingly emphasized, and may have an even greater impact on survival than choice of revascularization modality. To quantify the impact of these PCI enhancements, the SYNTAX II investigators performed PCI in 454 patients at 22 centres with three-vessel disease in whom the SSII predicted equipoise between PCI and CABG. Outcomes were compared with 315 PCI and 334