JAMA reanalysis goes against 5-year Abbott stent study findings, upping odds of death

Dive Brief:

A Bayesian reanalysis of five-year clinical trial data found coronary artery bypass surgery, also referred to as CABG, yields better results in left main coronary artery disease patients than Abbott’s Xience stent, going against the controversial conclusion of the original analysis. Findings from the reanalysis were published in JAMA Internal Medicine on Monday,.
With the reanalysis putting the probability of more deaths in the Xience arm at 99%, a Cedars-Sinai Medical Center cardiologist used the study to call for revascularization guidelines to stop recommending PCI for low-complexity left main patients.
Abbott, which funded the original study, did not have an immediate comment regarding the reanalysis of the Evaluation of Xience versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) trial data.

Dive Insight:

Release of five-year data from the Abbott-funded EXCEL clinical trial in the New England Journal of Medicine last November could have been the moment that a long-running debate about the merits of PCI and CABG was put to rest. Instead, the presentation further fanned the flames, most explosively when the former chairman of the study’s surgical committee argued its conclusions were at “complete odds” with the data. The surgeon, David Taggart, withdrew his name from the paper over the dispute.

The controversy centered on the claim that Xience was noninferior to CABG in terms of the risk of death and major cardiovascular events. As Taggart saw it, the data showed “a strong benefit” in favor of CABG over PCI that the conclusions of the study failed to reflect.

In response to the controversy, James Brophy of McGill University Health Center reanalyzed the data. Brophy’s conclusions are more in line with Taggart’s position than the findings of the original paper.

The reanalysis found a 99% probability that EXCEL total mortality was increased with PCI. Additionally, the probability that PCI is associated with an increased mortality risk of 1% or more is 94%. The chances of PCI increasing the risk of major adverse cardiac and cerebrovascular events are higher still. Taking a slightly different analytical approach brought some of the figures down, but not by enough to lead Cedars-Sinai Medical Center’s Sanjay Kaul to change his position.

“The pooled mortality benefit of CABG remains, although moderated. Thus, the overall mortality results of the reanalysis by Brophy clearly favor CABG with additional reductions, compared with the use of PCI, in nonprocedural [myocardial infarction] and repeat revascularization procedures, and no increase in stroke,” Kaul, a cardiologist, wrote in a commentary published alongside the reanalysis.

Kaul said the reanalysis is compelling enough to change practices. Specifically, Kaul calls for European revascularization guidelines to drop a recommendation that PCI is used to treat left main patients with low anatomical complexity, reflecting a belief that Abbott’s data played a big part in the decision to support stenting. He accused the original paper of spin, pointing to a recent analysis of the rate of misleading conclusions in industry-funded presentations to highlight the extent of the problem.

In comments to Cardiovascular Research Foundation publication TCTMD, EXCEL principal investigator Gregg Stone called out shortcomings of the reanalysis, saying it "combined apples with oranges."

Other studies, such as a 10-year comparison of PCI and CABG, have found results achieved by the two approaches are similar. After seeing the 10-year data, Deepak Bhatt, the executive director of Interventional Cardiovascular Programs at Brigham and Women's Hospital, said “either approach is fine in terms of hard outcomes” but that he still favored CABG in patients with few comorbidities and low stroke risk.

The EXCEL study assessed Abbott’s Xience everolimus-eluting stents but the findings of the reanalysis could have implications for other devices used in PCI. Boston Scientific’s Synergy products are also used in the stenting of left main patients.