乌鸦传媒

MUNICH -- Abbreviated dual antiplatelet therapy (DAPT) with ticagrelor (Brilinta) was no better for preventing death or non-fatal MI after stenting than a standard drug regimen in the reported here.

In the study, 15,968 patients who got percutaneous coronary intervention (PCI) with a biodegradable-polymer stent were randomized to short DAPT (ticagrelor plus aspirin for 1 month after PCI, then ticagrelor alone for 23 months) or a more conventional regimen: 1 year of DAPT with clopidogrel (Plavix) or ticagrelor plus aspirin for the first 12 months, followed by aspirin monotherapy for another 12 months.

The short DAPT group had similar rates of all-cause mortality or non-fatal MI over 2 years (3.81% versus 4.37%, RR 0.87, 95% CI 0.75-1.01), whether or not patients had presented with an acute coronary syndrome (ACS) or stable coronary artery disease (CAD), reported Patrick Serruys, MD, PhD, of of Erasmus Medical Center in the Netherlands, at the European Society of Cardiology meeting.

Serruys and his GLOBAL LEADERS collaborators also published the results online in .

"We hypothesised that the use of ticagrelor without concomitant aspirin could preserve ischaemic protection while potentially avoiding bleeding complications," the authors noted.

To that end, investigator-reported rates of Bleeding Academic Research Consortium (BARC) grade 3 or 5 bleeding were indeed comparable between the short- and standard-DAPT groups (2.04% versus 2.12%, RR 0.97, 95% CI 0.78-1.20).

Additionally, definite stent thrombosis occurred in 0.80% in both arms at 2 years (RR 1.00, 95% CI 0.71-1.42).

Overall, the "experimental regimen had no clear benefits and no clear harms either," said Deepak Bhatt, MD, of Brigham and Women's Hospital in Boston, in an .

"However, in view of the higher rates of discontinuation, the increased frequency of dyspnea, and the higher cost associated with the experimental regimen than with the control group, as well as the necessity of twice daily dosing with ticagrelor, aspirin should remain the preferred antiplatelet therapy for secondary prevention," he urged.

The trial shouldn't lead to any change in practice, though aspirin monotherapy can still be improved upon, according to Bhatt.

Sunil Rao, MD, of Duke University Medical Center in Durham, N.C., also came away concluding that standard DAPT should stay the way it is.

What was "impressive" to Rao was the "incredibly low rate of stent thrombosis in both arms," he told 乌鸦传媒.

GLOBAL LEADERS was conducted in 18 countries and ended up with a study population that averaged 64.5 years of age and was 23.3% women.

PCI was performed with a biolimus A9-eluting stent from the BioMatrix family of biodegradable-polymer stents from Biosensors.

"The data on biodegradable polymers is mixed. Whether these data apply to all stents is not clear, but my gut tells me that they probably do. Drug-eluting stents have evolved to the point where they are very safe," Rao said.

A blinded core lab provided adjudication of new Q-wave MIs.

The exact DAPT regimens that patients got were either 75-100 mg aspirin daily plus 90 mg ticagrelor twice daily for 1 month, then 23 months of ticagrelor alone; or standard DAPT (12 months of with aspirin plus 75 mg clopidogrel daily in the case of stable CAD or 90 mg ticagrelor twice daily for ACS) followed by aspirin monotherapy for 12 months.

GLOBAL LEADERS is the largest trial yet in the interventional space to examine a strategy to simplify DAPT post-PCI, commented Roxana Mehran, MD, of Mount Sinai Hospital in New York City, who was not involved in the trial.

"Overall, I actually think that despite missing the primary endpoint, the study is a huge milestone in our quest to improve safety and efficacy of DAPT post-PCI, and in finding ways to simplify the regimen without harming patients," she told 乌鸦传媒 in an email.

Nevertheless, the study suffered from an open-label design that had implications for patient compliance, she said, "and this is really the biggest issue."

Over the 2 years of the study, adherence to assigned treatment had dipped to 77.6% and 93.1% in the experimental and reference ticagrelor arms, respectively.

Another limitation was the non-adjudicated endpoints of bleeding and stent thrombosis, Mehran said. "While the hard endpoint of death (all cause) is important, and actually trends in favor of the experimental arm, I am concerned that we miss the importance of bleeding benefit by only evaluating investigator-reported events, which can be biased."

Finally, she called the control arm "a mixed bag of different therapies" that makes it difficult to understand how each contributes to a particular issue.

The next trial to watch out for is TWILIGHT, a trial evaluating ticagrelor monotherapy after a 3-month course of DAPT. The trial is slated to be presented later this year.

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