Higher Mortality With Off-Pump CABG: EXCEL Analysis

Off-pump coronary artery bypass grafting is associated with a significantly higher rate of all-cause mortality than surgery with cardiopulmonary bypass in patients with left main disease, according to a new analysis from the EXCEL trial. This higher mortality risk was particularly pronounced in patients with extensive coronary artery disease.

A lower rate of revascularization of the left circumflex and right coronary arteries with off-pump surgery likely contributed to the worse outcomes, the investigators suggest.  

“With left main disease, you have two territories to revascularize,” lead investigator Umberto Benedetto, MD, PhD (University of Bristol, England), told TCTMD. “With distal lesions, it’s a single lesion in a single territory, but with left main disease you have the entire myocardium at risk for ischemia. What we found was that off-pump was associated with a significantly lower rate of revascularization of the lateral wall, which should be revascularized for patients with left main disease.”

In the vast majority of cases, CABG surgery should be performed with cardiopulmonary bypass, Benedetto added. “For left main disease with a relatively large area of ischemia, on-pump should really be the first line of approach unless it’s performed in a center experienced in the off-pump technique.”

For left main disease with a relatively large area of ischemia, on-pump should really be the first line of approach unless it’s performed in a center experienced in the off-pump technique. Umberto Benedetto

Surgeon Joanna Chikwe, MD (Cedars-Sinai Medical Center, Los Angeles, CA), who was not involved in the analysis, said these new data “confirm the consensus view that for most patients who need surgical revascularization for multivessel coronary disease, on-pump CABG remains the gold standard.”

Michael Mack, MD (Baylor Scott & White Heart Hospital, Plano, TX), agreed. The present study, like other trials comparing on- versus off-pump CABG surgery, shows that off-pump is associated with less complete revascularization and this translates into a higher risk of death. “The message from this [EXCEL] analysis is that if a surgeon is not preferentially doing off-pump surgery, they shouldn’t feel compelled to do it because of these results,” Mack told TCTMD. “They should stay with their results and what they’re best at. For the majority of surgeons, that’s going to be on-pump surgery.”  

EXCEL and Left Main CAD 

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 patients at low-to-intermediate risk. Results showed that PCI had comparable rates of death, stroke, or MI at 3 years as the surgical approach.

In the trial, 923 patients were randomized to the surgical revascularization arm, including 652 and 271 patients who underwent CABG with and without cardiopulmonary bypass. The decision to perform on- or off-pump surgery was at the discretion of the operator, but the baseline patient and angiographic   characteristics were largely similar between the two surgeries. Patients undergoing off-pump surgery had significantly fewer vessels bypassed and fewer grafts, however. As noted, off-pump surgery was also associated with a lower rate of revascularization of the left circumflex artery and right coronary artery.

At 3 years, there was no significant difference in the risk of all-cause mortality, MI, or stroke between the two surgical procedures. All-cause mortality, on the other hand, was significantly higher among patients who underwent CABG without cardiopulmonary bypass (8.8% vs 4.7%; P = 0.02). The increased risk of death was largely driven by a higher rate of cardiovascular mortality (5.8% vs 3.0%; P = 0.05). The treatment effect remained significant in an analysis accounting for imbalances in the pretreatment variables between surgical groups.

The message from this [EXCEL] analysis is that if a surgeon is not preferentially doing off-pump surgery, they shouldn’t feel compelled to do it because of these results. Michael Mack

The SYNTAX score was the only significant modifier for the treatment effect of off-pump versus on-pump surgery. For example, off-pump surgery was associated with a higher risk of death, MI, or stroke (HR 1.72; 95% CI 1.00-2.98) and a higher risk of all-cause mortality (HR 3.01; 95% CI 1.45-6.26) in individuals with a SYNTAX score ≥ 23 but not in those with a score < 23.

To TCTMD, Chikwe explained that while some surgeons perform off-pump surgery as the default approach, the majority perform the procedure in only selected patients, such as those with calcification of the ascending aorta, end-stage renal disease (non-dialysis dependent), and severe pulmonary disease. In EXCEL, roughly 30% of patients randomized to surgery underwent the off-pump procedure. In real-world clinical practice, however, approximately 15% to 20% of CABG surgeries are performed without cardiopulmonary bypass.

These new EXCEL results confirm previously published data by Chikwe and colleagues comparing long-term outcomes after off-pump and on-pump CABG by experienced surgeons. In that 2018 analysis, individuals who were treated off-pump received fewer grafts and less complete revascularization than those who underwent on-pump CABG surgery.

“Importantly, incomplete revascularization was one of the strongest predictors of worse mortality,” said Chikwe. “It is technically more challenging to expose the circumflex and right coronary artery territories off-pump without causing ischemia requiring emergency conversion to on-pump surgery.”

Mack noted that while there was a statistically significant difference in the number of bypass grafts between the two procedures in the EXCEL trial—2.3 grafts with off-pump CABG versus 2.7 grafts with on-pump CABG—as well fewer bypassed vessels in patients undergoing off-pump surgery, the between-group difference was “underwhelming” as an explanation for the mortality effect.

Off-Pump CABG Best Left to Experienced Surgeons

In an editorial, Faisal Bakaeen, MD, and Lars Svensson, MD, PhD (both Cleveland Clinic, OH), state it’s possible that less revascularization of arteries supplying the inferolateral wall might contribute to the higher rate of death in patients with left main coronary artery disease. “A ruptured or thrombosed left main atherosclerotic plaque is obviously more consequential than a ruptured plaque in any other coronary location in patients who are not protected by functional bypass grafts to distal targets,” they write.

In North America, use of off-pump CABG peaked at nearly 25% of procedures in 2002, but has been declining since then. Like Mack, Bakaeen and Svensson state that off-pump CABG is best left to experienced surgeons skilled in the technique or used only for select high-risk patients, such as those with advanced cirrhosis or atheromatous disease of the ascending aorta.

Within the surgical realm, Chikwe said next important steps include defining the benefits of multiple arterial grafts versus a single arterial graft, which is being tested in the ROMA trial, as well as evaluating the efficacy of a hybrid approach that combines the long-term benefits of a LIMA to LAD bypass through a minimal incision with PCI to the other territories. “These will be the definitive surgical approaches that drive real improvements for patients with coronary disease in contemporary practice,” said Chikwe.