By Jeffrey Zimmet, MD, PhD
Associate Professor of Medicine, University of California, San Francisco; Director, Cardiac Catheterization Laboratory, San Francisco VA Medical Center
SYNOPSIS: In this analysis of the SYNTAX Extended Survival study, the presence of one or more bifurcation lesions resulted in a higher risk for all-cause death among patients who were treated with percutaneous coronary intervention.
SOURCE: Ninomiya K, Serruys PW, Garg S, et al. Predicted and observed mortality at 10-years in patients with bifurcation lesions in the SYNTAX trial. JACC Cardiovasc Interv 2022; May 10:S1936-8798(22)00847-0. doi: 10.1016/j.jcin.2022.04.025. [Online ahead of print].
The choice of revascularization tactics for patients with left main and multivessel coronary disease has been an area of active clinical investigation. The authors of the SYNTAX trial compared coronary artery bypass grafting (CABG) with percutaneous coronary intervention (PCI) in such patients and developed an angiographic score (the SYNTAX score) that is designed to assess total burden of coronary disease and lesion complexity. These scores tend to be involved enough that they can be difficult to use in clinical practice. What if individual, easily parsed lesion characteristics could be used to help make clinical decisions?
Bifurcation lesions are found in a significant proportion of patients with multivessel disease and have been associated with higher rates of both short- and intermediate-term adverse events after PCI. The SYNTAX Extended Survival study (SYNTAXES) was a 10-year follow-up of the SYNTAX trial, a multicenter trial in which 1,800 patients with left main or multivessel coronary disease were randomized to either CABG or PCI with the Taxus paclitaxel-eluting stent. A prespecified subgroup analysis of SYNTAXES sought to describe the effects of bifurcation lesions on long-term outcomes after PCI and CABG, and to compare predicted and observed mortality in these patients.
Of the original 1,800 patients in the SYNTAX trial, 1,787 were included in this study. Of these, 1,300 had at least one bifurcation lesion, while 487 patients did not. Patients with bifurcation lesions were older, exhibited a greater number of total lesions, and recorded higher SYNTAX scores compared with those without.
At five years, the presence of a bifurcation lesion led to a higher risk of subsequent revascularization among patients treated with PCI (26.7% vs. 19.4%; HR, 1.50; 95% CI, 1.08-2.08; P = 0.016), but not for those treated with CABG. Patients with at least one bifurcation lesion had numerically higher rates of death, stroke, and myocardial infarction at five years, but this did not reach statistical significance. At 10 years, all-cause mortality was significantly higher among PCI patients with one or more bifurcation lesions (30.1% vs. 19.8%; HR, 1.55; 95% CI, 1.12-2.14; P = 0.007) compared to those without. In contrast, patients treated with CABG recorded similar rates of all-cause death, regardless of bifurcation status (23.3% vs. 23%; P = 0.207). Notably, the lowest mortality at 10 years was among those patients without bifurcation lesions who were treated by PCI (19.8%).
Among 512 patients with bifurcations who were treated with PCI, 70% were treated with a one-stent technique, while 30% were treated with at least one two-stent technique. Patients who underwent a two-stent technique showed a significant increase in repeat revascularization at five years, but no change in mortality. However, at 10 years, the use of a two-stent technique was an independent predictor of all-cause death.
The authors concluded the presence of at least one bifurcation lesion was associated with an increased hazard for repeat revascularization at five years and for all-cause mortality at 10 years among patients treated with PCI, but not among those treated by CABG.
COMMENTARY
This study started with a simple, easy-to-understand hypothesis — bifurcation coronary disease adds significant complexity to PCI, which treats the lesion itself, but not to CABG, which relies only on a patent distal target. Longer-term follow up for cardiology studies is lacking in many areas, so data like these are valuable despite their shortcomings. The major strength of this study (i.e., long-term mortality data) also can be seen as a weakness, in that older technology and older techniques are in play. In this case, even older first-generation drug-eluting stents compared favorably with CABG in patients without bifurcations. Also, bifurcations are quite common among patients with multivessel coronary disease. Nearly three-quarters of patients in this trial had bifurcation disease, so the discriminatory value of this single variable may not be that high.
This trial provides valuable data suggesting worse long-term outcomes among patients with bifurcation disease undergoing PCI for multivessel disease. The conclusion that bifurcation disease leads to higher all-cause mortality at 10 years among patients treated by PCI should be considered by heart teams as they weigh revascularization options.
In this analysis of the SYNTAX Extended Survival study, the presence of one or more bifurcation lesions resulted in a higher risk for all-cause death among patients who were treated with percutaneous coronary intervention.
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