New data cast new light on EXCEL controversy
More complete data from the NOBLE trial didn't change a preliminary finding that patients with left main coronary artery disease did better after coronary artery bypass grafting (CABG) than stenting at 5 years.
On intention-to-treat analysis, rates of major adverse cardiac or cerebrovascular events over a median 4.9 years of follow-up were 28% and 19% among people who had been randomized to percutaneous coronary intervention (PCI) and CABG, respectively (HR 1.58, 95% CI 1.24-2.01), according to an update published online in The Lancet.
Stenting therefore failed to meet non-inferiority against CABG with the latter even showing superiority (P=0.0002), Evald Christiansen, PhD, of Aarhus University Hospital in Denmark, and colleagues concluded.
In 2016, a preliminary 5-year report had reached similar conclusions, though the trialists had not yet achieved the predefined number of events required for analysis at the time.
Now, having reached this required number of events for adequate power, NOBLE still shows that PCI is associated with inferior clinical outcomes compared with CABG after 5 years, Christiansen's group said.
Only two components of the primary endpoint pointed to a difference between stenting and surgery:
- Non-procedural MI: 8% vs 3% (HR 2.99, 95% CI 1.66-5.39)
- Repeat revascularization: 17% vs 10% (HR 1.73, 95% CI 1.25-2.40)
The other two did not differ significantly:
- Stroke: 4% vs 2% (HR 1.75, 95% CI 0.86-3.55)
- All-cause mortality: 9% vs 9% (HR 1.08, 95% CI 0.74-1.59)
The latter finding was numerically lower than the 13% observed in EXCEL's recent 5-year report. Non-procedural MI and repeat revascularization rates were similar between trials.
"These findings indicate that the quality of PCI in NOBLE was at least similar to that of EXCEL and the difference in primary outcome is likely to relate to definitions of endpoints," Christiansen and colleagues wrote. A difference in stenting quality had been proposed as one reason why the two trials came up with contradictory conclusions, the EXCEL investigators having given PCI non-inferiority to CABG at 3 years (and again at 5 years) in left main disease.
"The differences in outcomes in the early reports were probably better explained by differences in primary and secondary endpoint definitions and the reported follow-up time than by differences in the quality of PCI," the NOBLE investigators suggested.
Michael Mack, MD, of Baylor Scott & White The Heart Hospital in Plano, Texas, who was not involved in either trial, said much the same when contacted by MedPage Today.
"I think that the importance of these outcomes from the NOBLE trial, especially when viewed in the context of the EXCEL trial, highlight the importance of trial design, inclusion and exclusion criteria, determination of composite endpoints, as well as endpoint definitions," said Mack.
"These are all major determinants in answering the question being asked. How you ask the question matters," he told MedPage Today.
EXCEL's finding of PCI's non-inferiority in the left main came under fire recently as the investigators were accused of withholding unfavorable mortality and MI data. The controversy led the European Association for Cardiothoracic Surgery to withdraw its endorsement of left main guidelines that relied heavily on the trial.
In response to critics, the beleaguered EXCEL leadership denied wrongdoing and vowed complete transparency moving forward.
NOBLE was a non-inferiority trial from Europe that enrolled 1,201 patients with left main disease requiring revascularization in 2008-2015. Median age was 66.2 years in both groups, and just over one in five among the cohort were women. Stale angina was the indication for more than 80% of cases.
Operators were not blinded and were allowed to overrule assigned treatment at their discretion.
The updated NOBLE report included 592 people in each group. The first 73 patients in the PCI arm received first-generation drug-eluting stents, the rest getting the newer-generation BioMatrix Flex umirolimus-eluting stent.
Christiansen and colleagues reported no interaction for any of the tested subgroups. However, those with SYNTAX scores under 23 were markedly worse off after PCI compared with CABG (MACE 27% vs 14%, HR 2.05, 95% CI 1.41-2.98).
For Rita Redberg, MD, of the University of California San Francisco, the choice is clear: "This report, coming close on the heels of EXCEL makes clear that we should be recommending CABG as the revascularization strategy of choice for our patients with left main disease," she said. Redberg was not involved in the studies.
Nevertheless, the generalizability of NOBLE is limited given that participating hospitals had a demonstrated interest in left main PCI and that enrolled patients may not be representative of the general population with left main disease.
"Patients who are eligible for both PCI and CABG must be well informed regarding the benefits and risks associated with each procedure," the NOBLE investigators urged.
NOBLE was funded by Biosensors.
Christiansen and colleagues disclosed grants from Biosensors and personal ties to industry.
Source Reference: Holm NR, et al "Percutaneous coronary angioplasty versus coronary artery bypass grafting in the treatment of unprotected left main stenosis: updated 5-year outcomes from the randomised, non-inferiority NOBLE trial" The Lancet 2019; DOI: 10.1016/S0140673619329721
Read the original article on Medpage Today: NOBLE Update: CABG Keeps Edge Over PCI in Left Main CAD