PRECOMBAT: PCI Noninferior to CABG for Left Main Disease

April 04, 2011

April 5, 2011  (New Orleans, Louisiana) — PCI with a sirolimus-eluting stent or coronary artery bypass graft (CABG) surgery are appropriate options for the treatment of patients with unprotected left main coronary artery stenosis, according to the results of a study presented today at the American College of Cardiology (ACC) 2011 Scientific Sessions [1].

Presenting data from the Premier of Randomized Comparison of Bypass Surgery versus Angioplasty Using Sirolimus-Eluting Stent in Patients with Left Main Coronary Artery Disease (PRECOMBAT) trial, investigators report that the primary end point at one year--a composite of major adverse cardiac or cerebrovascular events (MACCE), including death from any cause, MI, stroke, and ischemia-driven target vessel revascularization--occurred in 26 patients assigned to PCI and 20 patients assigned to surgery, a cumulative event rate of 8.7% and 6.7%, respectively.

In a press conference announcing the results, Dr Seung-Jung Park (Asan Medical Center, Seoul, Korea) said the one-year MACCE rate met the statistical criteria for noninferiority (p=0.01), suggesting that PCI is a viable option in the treatment of unprotected left main coronary disease. However, as the group points out in the New England Journal of Medicine, published April 4, 2011 to coincide with the late-breaking clinical-trial presentation, the study was underpowered as a result of unexpectedly low event rates. The group had predicted a one-year event rate of 13% after CABG but instead observed much lower rates following CABG and PCI, event rates that were also lower than those observed in other randomized and nonrandomized trials.

Speaking with heartwire , Dr David Kandzari (Emory University, Atlanta, GA), who was not involved in the study, praised the PRECOMBAT investigators for addressing an important question, saying the group is ahead of the curve in tackling tough clinical issues in cardiovascular medicine, but noted that the trial was "woefully underpowered." He called the results an extension of the evidence currently available to interventionalists, but the findings, because of the limitations of the trial, are not enough to advance PCI to where it would be considered a routine alternative to bypass surgery.

"Overall, this trial is a modest advance on what we already recognize from the existing--and limited--randomized data and, more broadly, the observational data of left main PCI," said Kandzari. "That is, we have a remarkable consistency across trials of equipoise with regard to the so-called hard end points--death, myocardial infarction, and stroke--and at the same time we have seemingly consistent data showing that with existing drug-eluting stents, at least first-generation drug-eluting stents, repeat revascularization is still higher when compared with bypass surgery."

Recently, guidelines from the European Society of Cardiology (ESC) and a "focused guidelines update" from the American Heart Association (AHA)/American College of Cardiology were changed to state that PCI in the left main should be considered an alternative to surgery in patients at low risk for procedural complications. As reported by heartwire , the AHA/ACC guidelines for the management of patients with STEMI and guidelines on PCI gave stenting in unprotected left main coronary artery disease a class IIb, level of evidence B, recommendation. In Europe, as part of the newest ESC guidelines, coronary stenting of left main disease is a class IIa, level of evidence B, recommendation.

The PRECOMBAT Trial

In PRECOMBAT, investigators randomized 300 patients with unprotected left main coronary artery stenosis to PCI with a sirolimus-eluting stent or to CABG surgery. Patients were diagnosed with stable angina, unstable angina, silent ischemia, or non-ST-segment elevation MI and had an unprotected stenosis >50% of the diameter of the left main coronary artery. All patients were candidates for PCI or surgery.

At one year, PCI was noninferior to CABG in terms of the primary MACCE end point. Extended out to two years, the rate of MACCE was 12.2% among individuals who received PCI and 8.1% among surgical patients, a statistically nonsignificant difference. Regarding secondary end points, the composite of death, MI, or stroke occurred in 3.3% of PCI patients at one year and 4.0% of CABG patients. There was no statistical difference in this composite end point at two years.

Investigators did observe a statistically significant difference in the rate of ischemia-driven target vessel revascularization at two years. Among PCI patients, the rate of revascularization was 9.0% compared with 4.2% among patients treated with surgery (hazard ratio 2.18; 95% CI 1.10–4.32). At two years, definite or probable stent thrombosis occurred in two patients treated with PCI, while symptomatic graft occlusion occurred in four patients treated with surgery.

PCI vs Bypass Surgery in Different Subgroups

In subgroup analyses, higher MACCE rates were observed in patients with more coronary artery disease, with treatment trending toward benefit among patients with only left main disease treated with PCI, whereas there was a statistically significant threefold higher rate of MACCE in patients with left main and triple-vessel disease. In contrast, there was no statistically significant difference in MACCE rates based on SYNTAX scores.

To heartwire , Kandzari said that one of the major takeaway messages from the SYNTAX trial, another surgery vs PCI head-to-head comparison that included a large left main cohort, is that surgery should be considered in patients with the highest angiographic lesion complexity. "As patient complexity increases, whether it's measured by the SYNTAX score or patients have more multivessel disease, there is at least a benefit, or a point estimate, that seems to lean toward favoring bypass surgery," he said.

That appeared to be the message that panel members, gathered to discuss the PRECOMBAT trial following the late-breaking presentation, took from the study as well. Dr James McClurken (Temple University, Philadelphia, PA) said that while "it's clear that unprotected left main coronary artery disease can be treated interventionally, what we're learning is that there are subgroups that clearly are at greater risk for MACCE down the line, and I do think it's important to include target vessel revascularization as MACCE." While less complex lesions seem to have equal outcomes with surgery and PCI, at least out to two years in PRECOMBAT and three years in SYNTAX, there are some patients, including diabetics, "who have greater difficulty down the line."

Panel member Dr Bernard Gersh (Mayo Clinic, Rochester, MN) told the audience that his decision--surgery or PCI for a patient with left main disease--would be swayed by the extent of non–left main disease. If the patient had very diffuse disease or were diabetic, he would elect for surgery. He noted, however, that more data are coming.

One of the next major trials in left main disease is still many years away. Dr Gregg Stone (Columbia University, New York) noted that investigators are finishing up the planning stages of the EXCEL trial, a 3100-patient study comparing patients with left main disease randomized to bypass surgery or PCI with the everolimus-eluting Xience stent. The primary end point of the trial is death, MI, or stroke, with repeat revascularization as a key secondary end point. Despite PRECOMBAT being underpowered and questions remaining about exactly which subgroups benefit the most from PCI and surgery, Kandzari said this latest trial provides supportive evidence that clinicians can use when discussing the relative merits of PCI vs surgery to patients.

"When we think about statistics, relative-risk reductions, p values, and statistical power, none of that is relevant in the context of a bedside discussion with a patient and their family," Kandzari told heartwire . "What you can take away from trials like PRECOMBAT are measurements of estimates of risk and benefit. You can turn it into a story of the number needed to treat. So from PRECOMBAT, we can say to a patient your risk of death, myocardial infarction, or stroke is very similar, but we would need to treat 20 patients with bypass surgery to avoid one additional revascularization. Or you could say, for every 100 patients treated with PCI, five patients would have to come back for the treatment of a blockage. Taking these data, you can get something that is meaningful in a conversation with a patient.

The PRECOMBAT trial was funded by the Cardiovascular Research Foundation (Seoul, Korea), Cordis, and a grant from the Korean Ministry of Health.

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