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ESC: Ticagrelor Fails to Improve on Clopidogrel After Switch

— Single-center study contradicts PLATO in ACS patients

MedpageToday

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BARCELONA -- Switching from clopidogrel (Plavix) to ticagrelor (Brilinta) for dual antiplatelet therapy (DAPT) had no benefit in patients stented for an acute coronary syndrome (ACS), a Dutch center reported here, in contrast to results from the PLATO trial 8 years ago.

Rates of a composite of all-cause death, MI, stroke, and major bleeding within 1 year actually rose at Thoraxcentrum Twente in the Netherlands after the center adopted ticagrelor in place of clopidogrel (as recommended in guidelines) in May 2014, Clemens von Birgelen, MD, PhD, told attendees at the conference. (EuroIntervention also published the data .)

With clopidogrel, the composite's 1-year rate was 5.1%, which increased to 7.8% after the switch to ticagrelor (propensity-adjusted HR 1.75, 95% CI 1.20-2.55), he said.

No surprise: adverse events were driven by major bleeding with the more potent platelet inhibitor (2.7% for ticagrelor versus 1.2% for clopidogrel; adjusted HR 2.75, 95% CI 1.34-5.61). "This increase in major bleeding was observed despite more transradial procedures, less glycoprotein IIb/IIIa inhibitor use, and more proton pump inhibitor prescriptions during the ticagrelor period – three factors that are known to decrease bleeding risk," according to von Birgelen.

What his group also observed in the CHANGE DAPT study was that ticagrelor offered no reduction in ischemic events. This went against the findings of PLATO, a trial that reported fewer deaths and MIs associated with the drug in 2009 relative to clopidogrel. PLATO eventually led to guideline recommendations that ACS be treated with DAPT consisting of aspirin and ticagrelor in lieu of clopidogrel).

Von Birgelen's new data may reflect current practice and use of newer-generation drug-eluting stents. The prospective, observational study of 2,062 consecutive patients -- all of whom underwent percutaneous coronary intervention (PCI) -- was designed to test whether outcomes in the ticagrelor period (2014-2015) at his center were non-inferior to the clopidogrel era's (2012-2014).

He warned that CHANGE DAPT's findings are not applicable to ACS patients not receiving PCI.

It is possible that propensity-matching left some confounding in a population that had more peripheral artery disease in the clopidogrel era and was on average 1 year older after the transition. The study also lacked data on pre-PCI medications and angiographic and procedural variables, and may have been marred by a "non-trivial" 15% crossover rate by 1 year, among other limitations, commented Davide Capodanno, MD, PhD, of Italy's Ferrarotto Hospital, in a EuroIntervention .

Nonetheless, CHANGE DAPT is "a piece in a mosaic of studies" that find no advantage with ticagrelor for ACS, von Birgelen said at a press conference. These include the TOPIC study, which showed that clopidogrel can be switched in for ticagrelor after just 1 month without sacrificing safety.

"This strategy is sometimes embraced in clinical practice, being perceived as safer than the standard one-year term of prasugrel or ticagrelor recommended by guidelines, particularly in categories of patients at high risk of bleeding," Capodanno said.

"The rationale for this approach rests in the belief that prasugrel and ticagrelor will exert their maximal benefit over clopidogrel in the early phase, which is actually not true when looking at landmark analyses of pivotal trials suggesting that the benefit continues in the long term," he continued.

Guidelines being guidelines, von Birgelen told ľֱ that his center won't just switch back to clopidogrel anytime soon.

Another study is needed, he said. "But clopidogrel's cheap, so it's not an interest of industry to perform such a study. Maybe public health should take the initiative."

  • author['full_name']

    Nicole Lou is a reporter for ľֱ, where she covers cardiology news and other developments in medicine.

Disclosures

Von Birgelen disclosed institutional research grants from AstraZeneca, Biotronik, Boston Scientific, and Medtronic.

Primary Source

EuroIntervention

Zocca P, et al "CHANGE DAPT: clopidogrel or ticagrelor in acute coronary syndrome patients treated with newer-generation drug-eluting stents" EuroIntervention 2017.

Additional Source

EuroIntervention

Capodanno D, et al "Dual antiplatelet therapy after acute coronary syndromes: no time for a CHANGE" EuroIntervention 2017;