Complex PCI Favors Long-term Ticagrelor Monotherapy: GLOBAL LEADERS

Patrice Wendling

May 28, 2019

PARIS — Long-term ticagrelor monotherapy after 1-month dual antiplatelet therapy (DAPT) may be a better option for patients undergoing complex percutaneous coronary intervention (PCI), suggests a new post hoc analysis of the GLOBAL LEADERS trial.

As previously reported, the main analysis showed ticagrelor 90 mg twice daily for 2 years with only 1 month of aspirin was not superior to standard 1-year DAPT followed by 1 year of aspirin alone for the composite primary end point of all-cause mortality or new Q-wave myocardial infarction (MI) at 2 years. Patients had undergone stenting for acute coronary syndrome or stable coronary disease.

In the new analysis of complex PCI, however, the strategy of ticagrelor monotherapy shows a significant 36% lower relative risk for the primary composite end point death (P = .015 for interaction).

The two components of the primary end point, all-cause mortality and new Q-wave MI, also show a 33% and 47% risk reduction, respectively, with ticagrelor monotherapy vs standard DAPT but failed to achieve significance for interaction.

Importantly, the benefit of long-term ticagrelor monotherapy was greater as the number of high-risk features increased in the complex PCI patients, Patrick Serruys, MD, PhD, Erasmus Medical Center, Rotterdam, the Netherlands, said here at the Congress of the European Association of Percutaneous Cardiovascular Intervention 2019.

Complex PCI was defined as diffuse multivessel disease, at least three stents implanted, at least three lesions treated, a bifurcation with at least two stents implanted, or a total stent length of more than 60 mm — all high-risk features identified in the 2018 European Society of Cardiology/European Association for Cardio-Thoracic Surgery guidelines for myocardial revascularization. In all, 4570 patients were in the complex PCI group and 11,880 in the noncomplex PCI group.

At 2 years, there was a 20% relative risk reduction in patient-oriented composite events (POCE) — defined as all-cause mortality, all stroke, all MI, and all revascularization — in the complex PCI group treated with ticagrelor monotherapy but not in the noncomplex PCI group (P = .017 for interaction).

The risk for BARC type 3 or 5 bleeding was similar between the two strategies, whereas net adverse clinical events — defined as POCE plus BARC 3 or 5 bleeding — favored ticagrelor monotherapy in patients with complex PCI but not in those with noncomplex PCI (P = .011 for interaction).

"Why is this important? The patients who undergo complex PCI have a higher risk of ischemic and bleeding events at 2 years, compared with the noncomplex PCI group," Serruys said. "I didn't have the time to show you these data but they are very clear."

He noted that the primary end point was significant at 1 year in the main analysis and likely just missed statistical significance at 2 years because adherence fell to just 78% among patients receiving ticagrelor monotherapy vs 93% among those given standard DAPT.

Discussant Peter Jüni, MD, a GLOBAL LEADERS investigator and director of the Applied Health Research Centre at the University of Toronto, said the new post hoc results are biologically and clinically plausible but that the analysis was not prespecified and based on an essentially negative trial.

"Personally I believe, yes, there are very strong arguments that this could be correct, but as Patrick actually pointed out very carefully, this is all hypothesis-generating," he said. "We need to have more data in terms of replicating the findings here."

Speaking to theheart.org | Medscape Cardiology, Serruys said: "I felt justified in looking at what the European Society considered as dangerous situations and to do a post hoc on the GLOBAL LEADERS. And then, we had the surprise to see that in the post hoc hypothesis-generating analysis — call it as you want — the results were extremely encouraging and positive, even for the primary end point, which was extremely robust."

In addition, complex PCI patients comprise a quarter of the participants in the all-comers trial and, thus, are a common clinical scenario for physicians, he noted.

Serruys observed that additional research is needed before clinical practice can change, but also suggested aspirin may follow a similar fate as the early antiplatelet agent dipyridamole (Persantine).

"If you make a survey of your colleagues, whenever they deal with a very complex situation from the PCI point of view — a lot of metal and bifurcation, etc. — many of them spontaneously give a more selective P2Y12 [inhibitor], so ticagrelor or prasugrel," he said.

Serruys noted that results are expected to be reported later this year from the Acetyl Salicylic Elimination Trial (ASET) examining the safety of antiplatelet monotherapy with prasugrel in select patients who have undergone successful PCI after a loading dose of DAPT.

Also later this year, the TWILIGHT trial is expected to report on the impact of ticagrelor alone vs DAPT with aspirin plus ticagrelor for 12 months on reducing clinically relevant bleeding (efficacy) and major ischemic adverse events (safety) in up to 9000 high-risk patients who have undergone successful PCI and completed a 3-month course of aspirin plus ticagrelor.

Earlier this year, a prespecified substudy of GLOBAL LEADERS, known as GLASSY, in nearly half its patients with adjudicated ischemic and bleeding events, showed that ticagrelor monotherapy was noninferior to standard DAPT for the composite ischemic end point of death, MI, stroke, and urgent target vessel revascularization at 2 years. Bleeding rates were identical in the two groups.

Serruys reports receiving grant/research support and/or consulting fees/honoraria from Abbott, Biosensors, Medtronic, Philips/Volcano, Sinomedical Sciences Technology, SMT, and Xeltis.

Congress of the European Association of Percutaneous Cardiovascular Intervention (EuroPCR) 2019. Presented May 21, 2019.

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