Vincent Bargoin

May 23, 2017

PARIS, FRANCE — Switching to dual antiplatelet therapy (DAPT) with clopidogrel and aspirin 1 month after PCI for ACS, rather than continuing with DAPT consisting of ticagrelor (Brilinta/Brilique, AstraZeneca) or prasugrel (Effient/Efient; Eli Lilly/Daiichi Sankyo) with aspirin, was associated with fewer bleeding complications without raising the risk of ischemic events in the Timing of Platelet Inhibition After Acute Coronary Syndrome (TOPIC) study[1].

 "What's surprising is that in the fairly long history of post-ACS dual antiplatelet therapy [trials], no one, until now, has thought of making this switch," said Dr Thomas Cuisset (Timone Hospital, Marseille, France) when presenting the results at EuroPCR 2017. The study was also published online in the European Heart Journal at the same time.

The PLATO and TRITON studies showed that the new P2Y12 receptor antagonists ticagrelor and prasugrel provide an overall benefit compared with clopidogrel. But in those studies, according to Cuisset, the potency of the new P2Y12 antagonists compared with that of clopidogrel made a difference in ischemic events in the early post-ACS phase, with a bleeding risk emerging during the chronic phase.

This being the case, why not implement "a strategy integrating the dynamic risk," as Cuisset put it?

Two-Step Antiplatelet Strategy

The hypothesis was tested in 646 patients managed for ACS. All of them were treated for 1 month after PCI using one of the newer P2Y12 antagonists plus aspirin and were then randomized to continue the same DAPT or switch to clopidogrel plus aspirin for 11 more months.

At 1 month, the patients had not experienced any major bleeding events and, in particular, had not experienced any bleeding with a Bleeding Academic Research Consortium (BARC) classification of 2 or higher; BARC 2 bleeding is defined as overt bleeding requiring nonsurgical treatment, hospitalization, or medical evaluation.

The patients' mean age was 60 years. The study population was 82% men, and 40% of the cases of ACS were ST-segment-elevation MIs (STEMIs).

Angioplasty was performed via the radial approach in 96% of the patients, and the stents implanted were drug-eluting in 91% of cases. Initial dual therapy included prasugrel in 57% and ticagrelor in 43% of the cases.

Less Bleeding, No Change in Ischemic Events

At 1 year, the primary end point (death, urgent revascularization, stroke, or BARC ≥2 bleeding) had occurred in 13.4% of the patients in the clopidogrel-DAPT group compared with 26.3% in the group that remained on DAPT with the newer P2Y12 antagonists (RR 0.48; 95% CI 0.34–0.68]; P<0.01).  

The primary outcomes were driven by bleeding events. The incidence of BARC ≥2 bleeding was 4% in the group that switched to clopidogrel compared with 14.9% in the group that remained on the new P2Y12 antagonists (RR 0.30; 95% CI 0.18–0.50; P<0.01). Taking all the bleeding together, the figures are, respectively, 9.3% and 23.5% (RR 0.39; 95% CI 0.27–0.59; P<0.01).

As for ischemic events, their incidence at 1 month was not significantly different: 9.3% in the group that switched to clopidogrel compared with 11.5% in the group that remained on prasugrel or ticagrelor (RR 0.80; 95% CI 0.50–1.29; P=0.36).

"In patients with no complications at 1 month after angioplasty for ACS, two-step dual antiplatelet therapy is superior to maintaining the initial strategy for preventing bleeding without increasing ischemic events," concluded Cuisset.

Furthermore, as an added bonus, "the two-step strategy results in a significant cost reduction and confers a quality-of-life benefit."

Cuisset mentioned three limitations of the study: its single-center nature, its open-label design, and the fact that it was underpowered for infrequent events, especially mortality; the benefit was associated with a safety end point.

He also drew attention to the fact that a statistical result does not obviate the need to assess each patient's ischemic and bleeding risk profiles and that there needs to be a selection process for choosing candidates for the TOPIC strategy.

Cuisset declares consulting fees from Daiichi Sankyo and Eli Lilly, and speaker fees from Abbott Vascular, Astra Zeneca, Biotronik, Boston Scientific, Cordis, Daiichi Sankyo, Sanofi, Edwards, Eli Lilly and Medtronic. Disclosures for the coauthors are listed in the article.

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