EXCEL Deep Dive: Repeat Revascularization, Medical Therapy, and Anemia All Impact Patient Prognosis

SAN DIEGO, CA—A deep dive into the EXCEL trial at TCT 2018 provided some insights into the impact of various clinical and patient characteristics, including postprocedural medical therapy, baseline anemia, and the need for repeat procedures, on clinical outcomes following coronary revascularization with PCI or CABG for the treatment of left main coronary artery disease.

In one analysis, which was led by R. Jay Widmer, MD (Baylor Scott & White Health, Temple, TX), the use of guideline-recommended medical therapy was associated with significantly better prognosis 3 years after either surgery or PCI for left main coronary artery disease. Overall, patients treated with statins, aspirin, beta-blockers, and a P2Y12 inhibitor had a 32% lower risk of all-cause mortality, MI, or stroke compared with those who weren’t treated with such medical therapy. The benefit of optimal treatment was consistent in the PCI- and CABG-treated patients, say researchers.

“In SYNTAX, which looked at multivessel revascularization with PCI versus CABG, there was a substudy that showed people treated with optimal medical therapy did much better up to 5 years,” Widmer told TCTMD. In terms of risk reduction, there was a 36% decrease in mortality and a 27% decrease in the risk of death, MI, or stroke at 5 years in SYNTAX, a benefit that was above and beyond what was observed with revascularization.

“The idea behind this analysis was whether patients got the same bump—the same reduction in cardiovascular events—on guideline-directed medical therapy in the EXCEL trial,” said Widmer. “We wanted to see if it held true in multivessel coronary artery diseases versus left main coronary artery disease.”

In their analysis, which was presented today during a session dedicated to EXCEL substudies, investigators report that guideline-directed medical therapy was initially prescribed in 59.8% of patients who underwent PCI and 44.6% of patients who were treated surgically. Overall, individuals who received optimal medical therapy at discharge had a significant 34% lower risk of all-cause mortality, which was similar to the reduction in SYNTAX, and the benefit was consistent in the PCI and CABG study arms. “At 5 years, though, the event rates were so much higher in SYNTAX,” said Widmer. “It’s a little bit of a different scale. In terms of the primary endpoint, which was death, MI, or stroke, we didn’t see that benefit with guideline-directed medical therapy unless we dropped the ACE inhibitor.”

To TCTMD, Widmer said that patients in the EXCEL trial were quite healthy, noting that relatively few had left ventricular dysfunction, diabetes, or renal disease, all of which are indications for an ACE inhibitor or angiotensin receptor blocker (ARB). For example, one-third of patients had diabetes at baseline and approximately 15% had renal insufficiency. “The need to have an ACE inhibitor wasn’t there,” said Widmer. “So we had a mixed population—people who might have needed an ACE inhibitor and those that didn’t—and that probably clouded the analysis a little bit.”

Speaking during the session, Sorin Brener, MD (NewYork-Presbyterian Brooklyn Methodist Hospital), said that clinical data support the use of ACE inhibitors/ARBs in this patient population, “but there is less and less enthusiasm for using beta-blockers.” To TCTMD, Widmer agreed that data supporting the use of beta-blockers after PCI or CABG is a “little bit softer.” Beta-blockers were defined as part of “optimal medical therapy” if the patient had a prior MI, heart failure, or left ventricular ejection fraction ≤ 40% (or a history of heart failure).   

Patrick Serruys, MD, PhD (Imperial College London, England), said the prognosis of patients after PCI or CABG for left main coronary artery disease is likely “quite spectacular” if they quit smoking in addition to being treated with optimal medical therapy. For his part, Widmer agreed, adding that losing weight also would likely improve clinical outcomes.

EXCEL Presented 2 Years Ago: PCI Noninferior to CABG

In the EXCEL trial, which was led by Gregg Stone, MD (NewYork-Presbyterian Hospital/Columbia University Irving Medical Center, New York, NY), and presented 2 years ago at this same meeting, investigators randomized 948 patients with left main coronary artery disease of low to intermediate complexity to PCI with Xience (Abbott Vascular) and 957 patients to CABG.

The primary endpoint—a composite that included all-cause mortality, stroke, or MI at 3 years—occurred in 15.4% of patients treated with PCI and 14.7% of patients treated with CABG (P = 0.02 for noninferiority). In addition, the secondary endpoint, which included the risk of death, stroke, or MI at 30 days, was significantly increased among the surgical patients, with investigators reporting a particularly increased risk of periprocedural MIs in the CABG arm.

In another subanalysis presented today, which was led by Gennaro Giustino, MD (Icahn School of Medicine at Sinai, New York, NY), investigators assessed the prognostic relevance of repeat revascularization after PCI and CABG in the EXCEL trial. To TCTMD, Giustino also highlighted the SYNTAX trial, noting that repeat revascularization after PCI in SYNTAX was more common than after surgery and was associated with an increased risk of adverse events, particularly MI, over 5 years. But among those who underwent repeat revascularization, an increased risk of adverse events was observed in the PCI group but not in the surgical patients.    

“We know PCI is associated with a higher risk of revascularization compared with CABG,” Giustino told TCTMD. “Often repeat revascularization is criticized as an endpoint because it’s not as bad as having an MI or stroke. So the actual effect of repeat revascularization on prognosis is somewhat uncertain.”

In EXCEL, the need for repeat revascularization during 3-year follow-up was higher among patients treated with PCI compared with surgery (12.9% vs 7.6%; HR 1.73; 95% CI 1.28-2.33), but any revascularization after the index procedure was associated with worse outcomes irrespective of the initial revascularization strategy.

“If you needed a repeat revascularization, whether you had PCI or CABG as the index procedure, you had a worse prognosis in terms of an increased risk of all-cause and cardiovascular mortality,” said Giustino.

Repeat revascularization of the nontarget vessel—mainly the right coronary artery—was not associated with an increased risk of mortality, but repeat revascularization of the target vessel was associated with an increased risk of death (HR 2.29: 95% CI 1.26-4.17). Repeat revascularization of the left main coronary artery was associated with a sixfold increased risk of death at 3 years compared with not undergoing revascularization.

Overall, there was no evidence of an interaction between the index PCI and CABG for most of the subtypes of repeat revascularization, except for repeat revascularization of the left main coronary artery. Repeat revascularization of the left main artery among patients initially treated with PCI was associated with nearly a fivefold higher risk of death. There was a trend toward a higher risk of mortality patients undergoing surgical revascularization of the left main, but the risk was not statistically significant.

Effect of Anemia on Outcomes

In the third analysis, Prakriti Gaba, MD (Columbia University Irving Medical Center, New York, NY), reported that baseline anemia, which was documented in 24.8% of patients in the EXCEL trial, was strongly associated with an increased risk mortality, as well as cardiac death, bleeding, and the need for blood transfusions, compared with those without anemia (HR 1.88; 95% CI 1.24-2.84).  

“Baseline anemia has been shown to lead to higher rates of death, major adverse clinical events, mortality, and the need for transfusion, among other things, in patients with coronary artery disease undergoing revascularization procedures,” said Gaba. “However, very few studies, and no clinical trials, have actually explored the effect of this preprocedural characteristic on patients with left main coronary disease.”

In EXCEL, PCI in anemic patients was associated with a lower risk of bleeding at 30 days, as well as a lower risk of transfusion at 30 days, compared with anemic patients treated with CABG surgery, observed investigators. In her presentation, Gaba reported there was a significant interaction between baseline anemia and revascularization strategy for blood transfusions at 30 days and 3 years, but no interaction between PCI and CABG on the risk of death, MI, or stroke at 3 years or TIMI major/minor bleeding. 

In the final presentation, Ioanna Kosmidou, MD (NewYork-Presbyterian/Columbia University Irving Medical Center, New York, NY), reported that women had similar rates of definite cardiovascular hospitalization as men following the procedure but were more frequently hospitalized for a possible cardiovascular cause following PCI. Importantly, cardiovascular hospitalization was not an independent predictor of subsequent mortality.