It is a truth universally acknowledged that a trial comparing interventional strategies for left-main coronary artery (LMCA) disease launched more than a decade ago may not be entirely relevant to contemporary practice.
But in a field short on data from patients followed for such a long time after undergoing coronary stenting or coronary artery bypass surgery (CABG) for LMCA disease, lately a contentious issue, the new 10-year follow-up report of the PRECOMBAT trial holds some pertinent insights.
That seemed to be the consensus when the trial that had randomized 600 such patients in 2005 was presented online March 30 during the American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology (WCC) virtual conference.
PRECOMBAT, which had a prospectively planned follow-up of only 5 years, did not show significant differences in risk between LMCA percutaneous coronary intervention (PCI) or CABG for a complex composite primary endpoint or several secondary endpoints, including death from any cause, after at least 10 years. The actual follow-up time averaged 11.3 years.
By then, 29.8% of those who had been assigned to PCI and 24.7% of the CABG group had experienced the primary endpoint of major adverse cardiac or cerebrovascular events (MACCE) — consisting of death, myocardial infarction (MI), stroke, or ischemia-driven target-vessel revascularization (TVR). The adjusted hazard ratio for the difference didn’t reach significance.
The only component of the primary endpoint to show a significant 10-year difference between the groups, ischemia-driven TVR, had occurred in 16.1% of PCI patients and 8.0% of those who had been assigned to CABG, for a significant twofold adjusted risk in the PCI group.
However, by 10 years the study was greatly underpowered for all the endpoints, so the current analysis can be seen only as hypothesis-generating, emphasized Duk-Woo Park, MD, of Asan Medical Center, Seoul, South Korea, during his online presentation.
Park is also lead author on the 10-year PRECOMBAT analysis published the same day in Circulation.
Because PCI in the trial was performed with now-outmoded first-generation sirolimus-eluting stents, “our findings should be confirmed or refuted through 10-year or longer follow-up of the recent EXCEL and NOBLE trials involving contemporary drug-eluting stents,” Park said in discussion following his presentation of PRECOMBAT.
“I think what it definitely shows is that if we have a patient who is not a good candidate for coronary revascularization surgically, that we can expect an acceptable result with PCI of some high-risk patients. And was actually a pretty low-risk group in that the SYNTAX scores were pretty low,” Marc R. Moon, MD, a surgeon at Washington University School of Medicine, St. Louis, Missouri, said as an invited discussant after Park’s presentation.
However, “Almost every study of coronary surgical revascularization versus PCI shows a much higher revascularization rate with PCI,” Moon further pointed out. “So that’s just one of the things we have to accept for its capabilities, to be able to do PCI. That’s a risk we balance in each patient, and the patient needs to understand it, and the treating physician needs to understand it.”
One nagging concern in the LMCA trials comparing PCI and CABG has been the durability of saphenous vein grafts, which don’t have the longevity of arterial grafts. So the 10-year outcomes from PRECOMBAT are especially welcome for whatever insights it might have on that issue, said Glenn N. Levine, MD, an interventionalist at Baylor College of Medicine, Houston, Texas, also an invited discussant for the presentation.
“I’m struck by the target-vessel revascularization rate of only 8%” in the CABG group. Perhaps, Levine said, it’s explained by the trial’s liberal use of arterial grafts for CABG, a mean of two per case, and more sparing use of vein grafts at an average 0.7 per case, he proposed.
About 75% of patients in the PCI group and 71% in the CABG group had revascularization of the LMCA and two- or three-vessel disease; it was 41% for LMCA plus 3-vessel disease.
Complete revascularization in PRECOMBAT was achieved in 68% of PCI cases and 70% of patients assigned to CABG; the internal thoracic artery was used for revascularizations of the left-anterior descending coronary artery in 94% of that group.
“That’s very impressive,” said trial observer Frederick Welt, MD, University of Utah, Salt Lake City, about the high prevalence of arterial grafts in PRECOMBAT. “And not the norm here in the United States,” he noted at a briefing on the trial for journalists.
Welt also pointed out the very extensive use of intravascular ultrasound to guide the deployment of stents in the trial, 91% of cases, which in the United States and Europe is seldom done outside of research centers. “Perhaps that accounts for some of the lower event rates.”
Also uncharacteristic of contemporary practice was that the protocol specified that PCI patients — but not those assigned to CABG — undergo surveillance coronary angiography, which occurred 8 to 10 months after the procedure, noted an editorial accompanying the PRECOMBAT publication, from Fernando Alfonso MD, PhD, Hospital Universitario de La Princesa, Madrid, Spain, and Adnan Kastrati MD, PhD, Deutsches Herzzentrum München, Germany.
Such surveillance angiography, they write, “is no longer recommended and is potentially relevant because TVR (the main difference between the two strategies), is significantly affected by this practice. A close look to the TVR actuarial survival curves reveals that they start to diverge precisely at this time.”
The current results of PRECOMBAT “further expand our knowledge, providing compelling evidence that clinical equipoise, defined as uncertainty regarding the relative benefits of competing revascularization modalities, persists for patients with LMCAD and low-to-intermediate anatomic complexity,” Alfonso and Kastrati contend.
“However, the occurrence of revascularization failure at this critical site remains of concern considering its prognostic implications. The higher need for TVR in the PCI arm consistently seen in all LMCAD studies overshadows the long-term results of this strategy.”
In PRECOMBAT, 600 patients with unprotected LMCA disease were randomly and evenly assigned to one of the two revascularization strategies at 13 centers in South Korea from 2004 to 2009. The PCI and CABG groups fared about the same for the primary endpoint at both 1 year and 5 years.
At 10 years, respective rates were:
Primary endpoint: 29.8% for PCI, 24.7% for CABG (hazard ratio [HR], 1.25 [95% CI, 0.93 – 1.69])
Composite of death, MI, or stroke: 18.2 for PCI, 17.5% for CABG (HR, 1.00 [95% CI, 0.70 – 1.44])
Death from any cause: 14.5% for PCI, 13.8% for CABG (HR, 1.13 [95% CI, 0.75 – 1.70])
Ischemia-driven TVR: 16.1% for PCI, 8.0% for CABG (HR, 1.98 [95% CI, 1.21 – 3.21])
The only observed significant subgroup interaction for the primary endpoint at 10 years was for the extent of coronary disease (P = .048). In patients who underwent revascularization of LMCA plus 3-vessel disease, the rate was 40% for PCI patients and 25.6% for CABG patients (HR, 1.82 [95% CI, 1.16 – 2.86]).
It remains to be fully clarified how PRECOMBAT relates to other randomized trials that have informed the controversial question of best revascularization strategy in LMCA disease. Besides NOBLE and EXCEL, other studies trials to explore the issue include the ASAN-MAIN and MAINCOMPARE registries and the randomized trial SYNTAX-Left Main.
PRECOMBAT was funded by the CardioVascular Research Foundation of Seoul, South Korea. Park disclosed receiving grants from Daiichi-Sankyo, ChongKunDang Pharm, and Daewoong Pharm; personal fees from Edwards Scientific and Medtronic; and grants and personal fees from Abbott Vascular. Disclosures for the other authors are in the report. Moon disclosed receiving consultant fees and/or honoraria from Medtronic. Levine, Alfonso, and Kastrati have disclosed no relevant financial relationships.
American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology (WCC): Abstract 410-14. Presented March 30, 2020.