Patient-Level Data Supports PCI for Some Patients with Unprotected Left Main Disease

PCI has more recently been considered by some to be a viable option for treating patients with unprotected left main disease, and new patient-level data confirm similar safety and better survival with the percutaneous option compared with surgery in select patients. The results will potentially open the door to changes in standard practice, the study authors suggest.

Both US and European guidelines include class I recommendations to use CABG in patients with unprotected left main disease. PCI, on the other hand, is supported by class IIa or IIb recommendations—meaning it is or may be reasonable—for low-to-intermediate-risk patients in the United States. In Europe, PCI has a class I recommendation for patients with a Syntax score ≤ 22 and a class IIa recommendation for those with intermediate risk (Syntax score 23 to 32).

Although past studies have suggested a benefit with PCI over CABG in certain lower-risk patients, none has been able to definitively substantiate choosing the percutaneous option as standard practice. But operators haven’t shied away from using PCI in many of their patients with left main disease, with one of the highest-volume centers in the world reporting similar outcomes in patients treated with PCI and CABG in a registry study.

Now, as reported in the September 6, 2016, issue of the Journal of the American College of Cardiology, Rafael Cavalcante, MD, PhD (Erasmus University Medical Center, Rotterdam, the Netherlands), and colleagues have pooled patient-level data from a subgroup of the SYNTAX trial and the PRECOMBAT trial, obtaining results consistent with past findings.

‘A Safer Alternative’

Of the 1,305 patients with unprotected left main disease studied, the incidence of MACCE at 5 years was higher in those who received PCI instead of CABG (28.3% vs 23.0%; HR 1.23; 95% CI 1.01-1.55), but this difference was mainly driven by a higher rate of repeat revascularization with the former (HR 1.85; 95% CI 1.38-2.47). Notably, the procedures had comparable rates of all-cause death, cardiac death, and the composite safety endpoint of all-cause death, MI, or stroke (P = NS for all).

Subgroup analyses confirmed the main findings, but PCI appeared to carry a mortality benefit versus CABG in patients with isolated left main or left main plus one-vessel disease. Specifically, PCI was associated with 60% and 67% reductions in overall and cardiac mortality compared with CABG in these patients.

Additionally, compared with the original Syntax Score, the Syntax Score II demonstrated greater accuracy in predicting which patients would benefit from PCI over CABG. Those recommended for PCI using the Syntax Score II who underwent CABG had higher long-term mortality than those who received PCI (19.1% vs 5.8%; P = 0.018).

The study represents “the largest individual patient-level database in the published data so far,” which will allow for strong conclusions to be made, the authors say. Moreover, the findings “may question the class IIa guidelines recommendations for the intermediate Syntax subgroup,” they argue. “With [these] longer-term equivalent MACE rates in this much larger population, PCI may now be considered a safer alternative to CABG in this specific subset of patients.”

Calvalcante and colleagues point to the ongoing NOBLE and EXCEL randomized controlled trials “that will bring more and stronger evidence to this scenario.”

PCI ‘Preferable’ in Some, Not All

In an accompanying editorial, Stephan Windecker, MD, and Raffaele Piccolo, MD (University of Bern, Switzerland), write that the results are largely consistent with what has already been shown, but because “this pooled analysis entails approximately 80% of the entire patient population . . . it informs the long-term safety, efficacy, and durability of the two procedures.”

Moreover, “the equipoise between PCI and CABG for the safety composite endpoint is clinically meaningful and reassuring, as both myocardial infarction and stroke are associated with impaired prognosis, whereas repeat revascularization procedures mainly affect quality of life,” they add.

The comparison of the Syntax scores led to “another main finding” of the study, according to Windecker and Piccolo. As the Syntax Score II adds anatomic factors to the clinical prognostic variables used alone in the original score, it “allows for a more nuanced and individualized approach in treatment selection,” they say.

Ultimately, “this study suggests that avoiding the known risks of open heart surgery in favor of the less invasive percutaneous approach may be preferable in selected patients with [left main disease] and less advanced coronary artery disease,” the editorialists write. But “CABG will remain the treatment of choice among patients with advanced [left main disease] owing to the protection against proximal atherosclerosis progression, the remarkable decrease in the need for repeat revascularization . . ., and the more complete revascularization.”

Objectiveness Needed

The study is “a pretty big deal, not a really big deal,” Sandeep Nathan, MD (University of Chicago, IL), commented to TCTMD. “I wouldn’t escalate it to practice-changing status immediately . . . because these are adjusted—albeit patient-level—analyses of two very important trials. But these are historical trials in that so much has changed in the practice of interventional cardiology that it’s tough to say that we do any of those things anymore as they did in PRECOMBAT and SYNTAX.”

Still, Nathan said this analysis gives “a couple of important pearls.” First, in appropriately selected patients with straightforward left main disease, “the very least you can say is that there’s parity with bypass surgery, and perhaps there’s actually a mortality benefit.” While it would be expected that outcomes with second-generation DES would be better than what is seen here, “until EXCEL and NOBLE are done, we’re not going to know that definitively,” he added.

Also, the study gives a “a patient-level data point to navigate by, in addition to the Syntax II score, when we’re discussing revascularization options with patients,” Nathan said. “At the very least, you could say this is not level-one data, but this is pretty close to that and as close as we’re going to get in the foreseeable future.”

More and more, left main disease gets “unfairly lumped together. There’s left main disease and then there’s left main disease,” he commented. “This paper nicely parcels out the importance between delineating straightforward versus complex left main disease. . . . Once you’ve ascertained that there actually is left main disease, it would be very reasonable based on these data to preferentially go toward PCI.”

Nathan said all patients at his center are discussed by the Heart Team and a “significant proportion of these patients” end up receiving PCI. “It’s been like that for a while because once you build up some confidence from an institutional and from the technical perspective, we’re able to take care of those patients and see them through,” he said, adding that operators really need to do their due diligence with angiography, FFR, and even IVUS to decide on the appropriate strategy.

Acknowledgement of these data will likely be different “on either side of the Atlantic,” Nathan observed. “The Europeans have been well ahead of the Americans in terms of how aggressive their catheter-based revascularizations have been historically, and this is further validation of what they’ve been doing for a number of years. I think that the adoption based on this perhaps will be a little bit more tempered in the United States.”

But the most important takeaway from this study is that it “at the very least should motivate everybody to look at left main disease patients in a very objective fashion,” he concluded.

 

Related Stories:

• PCI Continues to Carve Out a Share of Unprotected Left Main Disease in the Absence of Definitive Evidence
• Outcomes at 5 Years Reinforce Durability of Stenting for Unprotected Left Main Disease
• Korean Registry Shows PCI Increasingly Used for Left Main Disease, With Improving Outcomes