TRYTON Published: Noninferiority Not Shown for Dedicated Bifurcation Stent

Provisional stenting remains the optimal strategy for treating true bifurcation lesions not involving the left main, according to results of the TRYTON trial, which did not show noninferiority for a dedicated bifurcation stent. The findings were published in the February 17, 2015, issue of the Journal of the American College of Cardiology.

Findings from the TRYTON trial also were previously presented at EuroPCR in 2014 and the Transcatheter Cardiovascular Therapeutics symposium in 2013.

Martin B. Leon, MD, of Columbia University Medical Center (New York, NY), and colleagues randomized 704 patients with true bifurcation coronary lesions at 58 international centers to treatment with DES in the main branch and either provisional stenting (n = 349) or the Tryton bifurcation BMS in the side branch (n = 355; Tryton Medical; Durham, NC) between December 2010 and November 2012. Baseline characteristics were well balanced, although those in the provisional stenting group were more likely to have had a prior MI.

All patients were followed for at least 9 months. Median follow-up was 366 days (range 4 to 840 days).

True bifurcation lesions—defined as at least 50% diameter stenosis in both the side branch and either distal or proximal main branch—were confirmed on angiography in 88.1% of the entire cohort, with similar proportions observed in the 2 groups. There were no between-group differences in the type of bifurcation or the characteristics of main branch lesions, but side branch lesions in the study arm were slightly more severe (diameter stenosis 58.0% vs 54.0%; P < .001) and longer (4.8 vs 4.4 mm; P < .001) than in controls.

Increase in Target Vessel Failure Due to Periprocedural MI

Within the bifurcation stent group, 96.1% of patients received the study stent. Side branch bailout stents were more frequently needed in the provisional vs bifurcation sent group (8.0% vs 2.8%; P = .02), but there was no difference in final kissing balloon inflation. Also, bifurcation stenting required longer procedures and more contrast on average compared with provisional stenting (P < .001 for both), but the former strategy was associated with higher lesion, procedure, and device success.

No patients in either arm died within 30 days of the procedure.

At 9 months, the incidence of target vessel failure (TVF; cardiac death, target-vessel MI, and clinically driven TVR in the main or side branch; primary endpoint) was similar between Tryton patients and controls (17.4% vs 12.8%; P = .11). However, the difference of 4.6% did not fall within the prespecified margin for noninferiority of 5.5% (P = .42 for noninferiority).

The higher rate of TVF for Tryton was driven by a numerically higher rate of periprocedural MI after bifurcation vs provisional stenting (13.6% vs 10.1%; P = .19). Stent thrombosis and mortality rates were low and similar in both groups. However, side branch in-segment diameter stenosis was lower with bifurcation stenting (31.6% vs 38.6%; P = .002 for superiority). There was no difference in in-segment binary restenosis for either the main (P = .85) or side branches (P = .44).

In post hoc analysis, an interaction was observed between treatment strategies and side branch size (baseline diameter < vs ≥ 2.25 mm by QCA) for the primary endpoint (P = .006) and target-vessel MI (P = .02; table 1).

According to the paper, these results show a “lack of benefit of the bifurcation 2-stent strategy in smaller [side branch lesions] and potential benefit in larger [ones]."

Side Branch Size Matters

“Small periprocedural CK-MB elevations… occurred more frequently with a 2-stent strategy and dominated the primary clinical endpoint,” they say, noting that the finding is consistent with 2 recent meta-analyses showing similar rates of death, revascularization, and stent thrombosis regardless of stenting strategy. The authors attribute the disparity in periprocedural MI to “more aggressive lesion preparation, increased coronary instrumentation, especially in smaller [side branch lesions], and longer procedural times.”

Dr. Leon and colleagues observe that there is a “well-known discrepancy between angiography (diameter stenosis severity) and biologic (CK-MB and troponin elevation) surrogate endpoints compared with hard clinical endpoints in coronary angioplasty clinical trials, if a certain threshold level of the surrogates is not reached.”

Coauthor Philippe Généreux, MD, also of Columbia University Medical Center, said that despite the negative results, the findings are “reassuring” and signal that dedicated bifurcation stenting may hold promise in patients with large side branches.

The key message, he told TCTMD in a telephone interview, is: “Don't waste time on small side branches, because… you're not going to reduce revascularization or death. You're only going to increase the risk of periprocedural MI without benefit.”

The TRYTON IDE XA registry is currently only enrolling patients with large side branches to test if the BMS is truly beneficial in this subgroup, Dr. Généreux reported. If that proves to be true, he said, the manufacturer might consider developing a DES version to improve outcomes further.

Limitations to Overcome

The biggest limitation of their study, the authors write, is that only 41% of enrolled patients met the entry criteria for side branch diameter size. “Although providing meaningful insights into the clinical relevance of treating [side branch lesions] with a dedicated [side branch] stent, the inclusion of ~60% of patients not meeting the inclusion criteria… reduced our capacity to demonstrate the value of a dedicated bifurcation stent strategy in true bifurcations with [side branches] of significant size,” they observe.

Additionally, they note, the newness of the device means that “learning curve issues must be considered.”

Future studies should “compare dedicated bifurcation devices with other novel stent technologies (eg, bioresorbable scaffolds)… [and] will better define optimum approaches to management of patients with bifurcation lesions undergoing percutaneous revascularization,” they say.

Provisional Prevails for Now

While the treatment of most bifurcation lesions is straightforward, the difficulty lies in predicting which bifurcations might be problematic, John A. Bittl, MD, of the Munroe Regional Medical Center (Ocala, FL), notes in an accompanying editorial. “Patients with diffuse disease in the [side branch] present a greater challenge than those with focal disease and have commonly been excluded from randomized controlled trials,” he explains.

Saving the side branch is “paramount” in every case, Dr. Bittl says, so the “search for dedicated bifurcation stent systems will continue.” He cites the “flower petal” technique and the Axxess (Biosensors; Singapore) and Multi-Link Frontier (Guidant; Santa Clara, CA) devices as potentially being able to maintain guidewire access to the side branch.

Dr. Bittl predicted that provisional stenting will “likely predominate in current practice over an approach using dedicated bifurcation stents or previous approaches using culotte, crush, or reverse-crush with multiple stents.”

Note: Dr. Leon and several coauthors are either faculty or staff members of the Cardiovascular Research Foundation, which owns and operates TCTMD.

Sources:
1. Généreux P, Kumsars I, Lesiak M, et al. A randomized trial of a dedicated bifurcation stent versus provisional stenting in the treatment of coronary bifurcation lesions. J Am Coll Cardiol. 2015;65:533-543.
2. Bittl JA. Treatment of bifurcation lesions: less is more [editorial]. J Am Coll Cardiol. 2015;65:544-545.

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