EXCEL Insights: CABG Outcomes for Left Main CAD Have Improved Substantially

The spotlight in recent years has been trained on improved outcomes using PCI for the treatment of left main coronary artery disease, but a new study reveals just how much surgical outcomes have also gotten better over a relatively brief period of time.

Compared with CABG-treated patients in the SYNTAX trial, which enrolled participants between 2005 and 2007, those enrolled in the EXCEL study and treated with CABG between 2010 and 2014 had a significantly lower risk of all-cause death, MI, stroke, and ischemia-driven revascularization at 3 years.

A key factor, say experts, is not the quality of the surgery per se but other aspects of care.

“One of the key messages of our study is that optimal medical therapy, or guideline-directed medical therapy, was way higher in the EXCEL patients, even when we look at 30 days of follow-up or 3 years of follow-up,” lead investigator Rodrigo Modolo, MD (Academic Medical Center, Amsterdam, the Netherlands), told TCTMD. “This might be one reason for the improvement and the major difference [between SYNTAX and EXCEL].”

Senior investigator Patrick Serruys, MD, PhD (Imperial College, London, England), also stressed the importance of guideline-directed medical therapy after revascularization of the left main coronary artery stem. “Secondary prevention is something that should be emphasized for both procedures,” Serruys told TCTMD.

The EXCEL study, which was presented at TCT 2016 and published in the New England Journal of Medicine, tested PCI against CABG surgery for the treatment of unprotected left main coronary artery disease in approximately 1,900 low-to-intermediate risk patients. Results showed PCI had comparable rates of death, stroke, or MI at 3 years as the surgical approach.

The older SYNTAX trial, on the other hand, included patients with three-vessel disease and left main coronary artery disease, and its 5-year results showed no difference in the overall MACE rate. The study hinted at a lower risk of death among patients with left main disease and low SYNTAX scores undergoing PCI, but better surgical outcomes among those with higher SYNTAX scores.

In the new analysis, published in the April 23, 2019, issue of the Journal of the American College of Cardiology, researchers wanted to determine if clinical outcomes in patients undergoing CABG for the treatment of left main disease had improved between SYNTAX and EXCEL, noting there has been some evolution in the procedure in the last decade. “When I look at SYNTAX with the Taxus stent, which was quite bulky, it was clear to me that with percutaneous interventions we had improved considerably, but I had some doubts about surgery,” said Serruys.

Improvement, but Why?

The propensity-matched analysis included 329 patients from SYNTAX and 580 patients from EXCEL undergoing CABG surgery. At 30 days, there was no significant difference in the risk of all-cause death, MI, stroke, and ischemia-driven revascularization between the study populations. However, the composite MACCE endpoint at 3 years was 20.9% in the SYNTAX patients and 14.0% in the EXCEL cohort (P = 0.008). The risk of death, stroke, or MI at 3 years was also significantly higher in the SYNTAX patients (14.0% vs 9.6%; P = 0.05). There was a trend toward lower mortality in EXCEL—8.5% at 3 years in SYNTAX versus 5.5% in EXCEL—but the reduction wasn’t statistically significant.

While the duration of bypass, cross clamping, and the surgical procedure itself were similar between groups, 29.6% of CABG surgeries in EXCEL were off-pump compared with 15.4% in SYNTAX. Use of an in situ left internal mammary artery (IMA) and the radial artery as a graft were more frequent in SYNTAX than in EXCEL, but there was no difference in the number of arterial or venous grafts or the use of bilateral IMAs. IMA grafts were used in more than 97% of patients in SYNTAX and nearly 99% of those in EXCEL (P = 0.08).   

“The interesting thing is that we can’t name names,” said Modolo. “We can’t say what’s responsible for the major improvement in outcomes of contemporary surgery. Of course, we have some differences in the surgical techniques—for example, we have nearly double the number of patients undergoing off-pump surgery [in EXCEL], although there is a longstanding debate about whether off-pump surgery is better than on-pump surgery. But what we have right now is the unknown. The data we have now don’t allow us to say off-pump is better, even though we had a lot of off-pump CABG in EXCEL.”

By contrast, the use of guideline-directed medical therapy was much better in EXCEL, including greater use of antiplatelet agents, lipid-lowering drugs, and beta-blockers. For example, at discharge more than 90% of EXCEL patients were prescribed a statin compared with just 75% of SYNTAX patients.

Benefit Not Explained by Off-Pump Surgery

Subodh Verma, MD (University of Toronto, Canada), a surgeon who was not involved in the study, said its general message—CABG-related clinical outcomes for left main disease have improved over time—is a good one for patients. “Whether it’s because of the surgery, pharmacotherapy, or systems of care, we do see over time there is an improvement in overall survival for people undergoing bypass surgery for left main, which is great news because we often just hear about this in the context of PCI,” he told TCTMD.

Verma said he doesn’t believe there’s been a massive technical advancement in CABG surgery between SYNTAX and EXCEL. While more off-pump procedures were performed, he pointed to 5-year results from the CORONARY investigators showing no significant difference in the risk of death, stroke, MI, renal failure, or revascularization between off-pump and on-pump CABG. The use of different conduits for revascularization is also unlikely to explain the difference.

Like Modolo and Serruys, Verma believes greater adherence to optimal medical pharmacotherapy explains the temporal improvement seen in EXCEL. “We know all these pharmacological therapies improve outcomes and they improve outcomes in the long term,” he said. “That’s represented in the data.” The outcomes for CABG in general are excellent, but the event rates between SYNTAX and EXCEL are quite similar at 30 days, he noted. “It argues for the fact that pharmacotherapy plays a very important role in further reducing event rates.”  

In an editorial, Patrick McCarthy, MD (Northwestern University Feinberg School of Medicine, Chicago, IL), praises both studies for the routine use of arterial grafts and stresses, like the others, that guideline-directed medical therapy should be prescribed after CABG to “slow the progressive nature of atherosclerosis, maintain graft patency, and reduce blood pressure.”

To TCTMD, Serruys noted that they are hoping to follow patients in EXCEL for at least 10 years and are working with industry to generate long-term follow-up data.