TWILIGHT Outcomes Hold Regardless of Stent Platform

Patrice Wendling

May 15, 2020

A new TWILIGHT analysis shows similar efficacy among high-risk patients treated with bioabsorbable polymer and durable-polymer stents and a consistent benefit of ticagrelor (Brilinta, Brilique; AstraZeneca) monotherapy.

At 1 year, the primary endpoint of target lesion failure (TLF) — a composite of cardiac death, target vessel myocardial infarction (MI), clinically indicated target lesion revascularization (TLR), or definite/probable stent thrombosis — occurred in 6.4% of patients treated with the everolimus-eluting Synergy BP-DES (Boston Scientific) and in 6.1% in patients treated with a conventional durable-polymer drug-eluting stent (DES) (adjusted hazard ratio [HR], 0.93; 95% CI, 0.64 - 1.35; P = .72).

The benefit was consistent across subgroups including diabetes, presence of multivessel disease, and stent length.

Rates of definite/probable stent thrombosis were also similar (0.8% vs 0.9%; adjusted HR, 0.70; 95% CI, 0.25 - 1.94), Usman Baber, MD, University of Oklahoma Medical Center in Oklahoma City, reported during the Society for Cardiovascular Angiography and Interventions (SCAI) 2020 virtual meeting.

"We all had great hopes for bioabsorbable polymers and we thought they would specifically be more prone to have less stent thrombosis after the polymer went away at 3 months, but it doesn't sound like — in this current generation, where some of the polymers are actually antithrombotic — that you saw much difference," panelist and SCAI 2020-2021 President Cindy Grines, MD, Northside Hospital Cardiovascular Institute, Atlanta, Georgia, said. "Is that your read on the study?"

Baber replied: "We don't see a significant difference and certainly one interpretation could be that the differences may be in the platform, in terms of say, strut thickness; 80 μm may not be large enough. Maybe once you get down to 60 μm or so, you start seeing those benefits."

He added, "With respect to the polymer, the safety advantage may be attenuated when you're comparing polymers that are truly biocompatible and arguably antithrombotic."

Follow-up also may not have been long enough, given that neoatherosclerosis and neointimal hyperplasia are later events.

In the parent TWILIGHT trial, discontinuing aspirin after 3 months on a background of ticagrelor monotherapy was superior to taking both agents for 1 year for the primary endpoint of BARC 2, 3, or 5 bleeding and was noninferior for the composite ischemic endpoint of all-cause death, MI, or stroke.

The benefit of ticagrelor monotherapy has held firm in subanalyses of patients with acute coronary syndrome or diabetes and in the recent TICO trial.

Prior randomized comparisons involving the Synergy BP-DES, however, have generally excluded high-risk patients and lesions, an important distinction as procedural complexity is a strong correlate of thrombotic risk after percutaneous coronary intervention, Baber pointed out.

The present prespecified analysis, TWILIGHT-SYNERGY, involved 5481 patients randomly assigned to receive either the Synergy BP-DES (n = 491), which consists of very thin (74 μm) struts, or a cobalt chromium durable-polymer stent (n = 4990). DES choice was at the physician's discretion.

Because enrollment was not stratified by stent type, there were some baseline imbalances, Baber noted. Those receiving the Synergy stent were more likely to be white, have a higher body mass index, and be enrolled in North America but were less likely to have a history of previous MI.

After adjustment, the Synergy and durable-polymer DES groups had similar outcomes for these secondary endpoints:

  • CV death or MI: 3.5% vs 5.0% (adjusted HR, 0.64; 95% CI, 0.40 - 1.04)

  • All-cause death: 0.9% vs 1.6% (adjusted HR, 0.54; 95% CI, 0.22 - 1.33)

  • TLR: 5.3% vs 4.4% (adjusted HR, 1.01; 95% CI, 0.67 - 1.53)

  • Target vessel MI: 1.6% vs 2.2% (adjusted HR, 0.73; 95% CI, 0.35 - 1.50)

Patients randomly assigned to ticagrelor monotherapy vs ticagrelor plus aspirin had numerically less BARC 2, 3, or 5 bleeding irrespective of whether they received the Synergy BP-DES (5.1% vs 8.2%; adjusted HR, 0.66; 95% CI, 0.32 - 1.37) or a durable-polymer DES (4.1% vs 6.7%; adjusted HR, 0.60; 95% CI, 0.47 - 0.77; P for interaction = .99).

Importantly, rates of death, MI, or stroke were similar between treatment groups among recipients of the Synergy BP-DES (3.4% vs 3.3%; adjusted HR, 1.27; 95% CI, 0.47 - 3.44) and conventional DES (3.9% for both; adjusted HR, 0.99; 95% CI, 0.74 - 1.31; P for interaction = .096).

Panel member Steven R. Bailey, MD, Louisiana State University Health Sciences Center in New Orleans, asked: "Since you had a relatively high bleeding risk rate, would there have been importance perhaps of backing this up to only giving 1 month of [dual antiplatelet] therapy, now that you've seen how safe it is, and would that have potentially shown differences in bleeding rates between the groups?"

"That question highlights how quickly this space is moving," Baber replied. "We got TWILIGHT started in 2015 and, at that time, we had to do a lot of convincing for a lot of investigators and regulatory bodies that this experiment was actually ethical. And now, the question you're proposing is exactly the right question, that actually we should be going shorter duration."

During a media briefing, Baber said the analysis should obviate some of the concerns that DES type may affect the risk-benefit calculus for ticagrelor monotherapy after PCI.

However, "the point estimates for the primary outcome were somewhat imprecise, indicating limited power, therefore we can't exclude the potential for a type II error," he said. "Therefore, our null results with respect to TLF should really be considered hypothesis-generating rather than conclusive inference."

Also, the results may not be generalizable to patients with ST-segment elevation MI or those without high clinical or angiographic features, who were excluded from the trial.

TWILIGHT was supported by a grant from AstraZeneca. Boston Scientific provided financial support for this prespecified analysis but had no role in the design, collection, analysis, or interpretation of the data. Baber reported advisory board/personal fees from Amgen, AstraZeneca, and Boston Scientific; and institutional research funding from AstraZeneca.

Society for Cardiovascular Angiography and Interventions (SCAI) 2020: Abstract 11754. Presented May 14, 2020.

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