Conference Coverage

VIDEO: Clopidogrel bests ticagrelor in PCI for ACS in real-world study



– Patients who underwent percutaneous coronary intervention for acute coronary syndrome using newer-generation drug-eluting stents backed by ticagrelor-based dual-antiplatelet therapy had significantly higher net adverse event rates at 1 year than did those with clopidogrel-based DAPT in the CHANGE DAPT study, Clemens von Birgelen, MD, reported at the annual congress of the European Society of Cardiology.

Based upon the CHANGE DAPT findings and those from other recent studies, it would be appropriate to revise ESC and American College of Cardiology/American Heart Association guidelines, which now give the newer, more potent platelet inhibitors ticagrelor (Brilinta) or prasugrel (Effient) preferential status as the P2Y12 inhibitor of choice over clopidogrel, added Dr. von Birgelen, professor of cardiology at the University of Twente in Enschede, the Netherlands, and codirector of the department of cardiology at Thoraxcentrum Twente.

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The current ESC guidelines giving ticagrelor preferential status over clopidogrel, as well as similar ACC/AHA guidelines, were based on the results of the randomized, double-blind PLATO trial, in which the use of ticagrelor resulted in significantly fewer ischemic events during follow-up than did clopidogrel-based DAPT (N Engl J Med. Sep 2009;361:1045-57). But PLATO, conducted nearly a decade ago, used bare-metal stents or first-generation drug-eluting stents (DES), which caused more ischemic complications than did the newer-generation, ultra-thin DES which were used exclusively in CHANGE DAPT.

“With the newer drug-eluting stents we see lower ischemic event rates, so the DAPT side effects due to bleeding become more important at this time. It could be that patients with ACS who are undergoing PCI may no longer need the most potent DAPT. Perhaps less potent DAPT with clopidogrel may be sufficient when using these more modern devices,” Dr. von Birgelen said in an interview.

CHANGE DAPT was a prospective, observational registry study that compared 1-year clinical outcomes in 2,062 consecutive ACS patients treated by PCI at Thoraxcentrum Twente, a high-volume PCI center. Half of the patients were treated before the primary DAPT regimen in the region changed from clopidogrel-based to ticagrelor-based DAPT on May 1, 2014, while the other half underwent PCI after the switch. This unique registry study design avoids selection bias, whereby cardiologists might preferentially use clopidogrel – the less potent P2Y12 inhibitor – in frailer patients.

The primary endpoint was the 1-year composite of all-cause mortality, any MI, stroke, or major bleeding. The rate was 7.8% in the ticagrelor period and significantly lower at 5.1% in the clopidogrel period. This difference was driven by the significantly lower major bleeding rate in the clopidogrel group: 1.2% versus 2.7% with ticagrelor-based DAPT.

The increased risk of bleeding associated with ticagrelor wasn’t offset by any advantage in term of ischemic events; indeed, the rate of such events was actually numerically lower with clopidogrel-based DAPT, albeit not statistically significantly so. Definite or probable stent thrombosis occurred in 0.6% of the clopidogrel group and 0.8% of the ticagrelor group, while the composite of cardiac death, MI, or stroke occurred in 3.7% of patients on clopidogrel-based DAPT compared with 4.7% on ticagrelor.

The two patient groups were closely similar at baseline in most respects, although the ticagrelor group was, on average, 1 year older, reflecting the more recent increased willingness of interventional cardiologists to utilize PCI in patients of advanced age. In terms of procedural differences, the ticagrelor group was more likely to undergo a transradial rather than transfemoral approach, less likely to receive a glycoprotein IIb/IIIa inhibitor, and more likely to get a proton pump inhibitor.

“All three of those factors should have reduced the bleeding risk during that second period,” Dr. von Birgelen observed.

In a propensity score–adjusted analysis taking account of the few between-group differences, ticagrelor-based DAPT was associated with a 1.75-fold increased risk of the primary endpoint and a 2.75-fold increased risk of major bleeding.

He noted that the CHANGE DAPT results are consistent with those of TOPIC, a 646-patient, single-center randomized trial conducted in Marseille. In TOPIC, after 1 month on ticagrelor- or prasugrel-backed DAPT, half of patients were switched to vastly less expensive clopidogrel for the remaining 11 months of DAPT. The result in the switched group was a marked decrease in bleeding with no increased risk of ischemic events.

“I see our study as a piece in a mosaic of studies and real-world registries with a similar message that have recently been reported,” the cardiologist said. “I hope the ESC looks carefully at these data.”

Session cochair Laura Mauri, MD, said that while it’s important to look at real-world observational data such as CHANGE DAPT to see if the results of randomized trials are generalizable, she’s not surprised by the evidence of increased risk of bleeding with a more potent agent such as ticagrelor.

“Why there’s a lack of benefit demonstrated, I think, is the bigger question,” said Dr. Mauri, professor of medicine at Harvard Medical School, Boston. “It could be related to changes in procedures over time, with procedures being conducted in a more complex manner, or some other residual confounding. I think whenever we see an observational study that changes the nature of the benefit that we see, it needs to be investigated more deeply. I don’t think it’s time to dismiss the results of very large randomized trials that show a meaningful benefit for the potent agents in the setting of ACS.”

CHANGE DAPT was an investigator-initiated study conducted without external funding. Dr. von Birgelen reported having no financial conflicts of interest.

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