Abandonment of aspirin: two trials explore P2Y12 monotherapy after a short-term post-PCI DAPT

NEW ORLEANS, LA – Two new trials indicate that short-term antiplatelet biotherapy followed by monotherapy with a P2Y12 inhibitor could bring more benefit than 12 months of DAPT in some patients with PKI receiving current generation SEM.

"[These two studies] We will really change the way we change the paradigm of "How long can you stop the P2Y12 inhibitor?" in "How long can you stop aspirin?" "said Claire Duvernoy, MD, University of Michigan, Ann Arbor), discussing both studies at a press conference held today at the 2019 Scientific Session of the American College of Cardiology (ACC). Is a big change in what we do. "

In addition, she added that the STOPDAPT-2 and SMART-CHOICE trials demonstrate that "the second-generation stents are impressive and are much more tolerant than the first-generation stents in which we had these subacute thrombosis. This is not trivial and it has all frightened us to continue dual antiplatelet therapy for long periods. This does not seem to be necessary, but changing what we give as monotherapy seems to be the important point here.

STOPDAPT-2

For the STOPDAPT-2 trial, Hirotoshi Watanabe, MD, Ph.D. (Kyoto University Hospital, Japan), presented the results, and his colleagues enrolled 3,045 patients on PCI with an eluting stent. cobalt chromium everolimus (EES, Xience, Abbott;) in 90 centers in Japan from December 2015 to December 2017. All patients received DAPT for 1 month (clopidogrel or prasugrel and aspirin). At this point, they were randomized to continue treatment with clopidogrel monotherapy or DAPT with clopidogrel and aspirin for one year. Notably, more than 97% of all patients received PCI guided by IVUS or OCT.

Clopidogrel monotherapy was greater than 12 months of DAPT for the primary endpoint of net adverse cardiovascular events (NACE); composite: cardiovascular death, MI, permanent thrombosis of the stent, stroke or major / minor bleeding with TIMI; 2.4% vs 3.7%; P superiority = 0.04) and secondary endpoint of major / minor TIMI bleeding (0.04% vs. 1.5%; P for superiority = 0.004). In addition, monotherapy with clopidogrel was not inferior to extended DAPT in terms of primary end-stage ischemia (composite: cardiovascular death, MI, definitive stent thrombosis, or stroke; 0% against 2.5%; P for non-inferiority = 0.005).

Rates of adverse events at 1 year were similar between arms of the study, with overall rates of thrombosis at the stent defined and likely very low.

Subgroup badyzes showed similar results, with the exception of patients with severe chronic kidney disease who were better off with 12 months of DAPT.

"One-month DAPT followed by clopidogrel monotherapy provided a clear clinical benefit for ischemic and bleeding events after 12-month DAPT treatment with aspirin and clopidogrel following Cobalt chrome SEE, "said Watanabe. "The benefit was driven by a significant reduction in hemorrhagic events without increased ischemic events."

Guest speaker Sunil Rao, MD (Duke Clinical Research Institute, Durham, North Carolina), congratulated the authors "for this very important study" and commented that the results "speak of the evolution of ICH and the security of OF. This is an interesting design in which you optimize the non-inferiority test for the MACE endpoint. The traditional approaches would have been to focus on non-inferiority on the ischemic effect criterion and superiority over the bleeding criterion, as we know that shorter durations of DAPT are badociated with less bleeding. "

In addition, co-moderator of the session, Martin Leon, MD (New York-Presbyterian Medical Center / Columbia University, New York, NY), said: "It's important to note that intravascular imaging was almost uniform in this study, almost 100%, which is extraordinary, which is the norm in Japan now. The very low event rates could therefore be partly related to intravascular imaging, which could mask a protective pharmacotherapy effect that we do not see. This is interesting in terms of generalizability on a global scale.

INTELLIGENT CHOICE

In the SMART-CHOICE study, presented at the same session last-minute trials by Joo-Yong Hahn, MD, PhD (Samsung Medical Center, Seoul, Korea), 2,993 patients receiving PCI with the current generation of DES (Xience, Promus), Synergy and Orsiro) in 33 Korean centers were randomized to maintain or discontinue aspirin after three months of DAPT treatment and followed for one year.

There was no difference between patients under DAPT in the short and long term with respect to the MACCE primary endpoint (all-cause death, MI or stroke; 2.9% vs. 2.5%, HR 1.19, 95% CI 0.76-1.85). was confirmed in a critical badysis at 90 days.

Clinical outcomes at 12 months were similar between study groups, with the exception of a higher rate of BARC 2-5 bleeding in those receiving 12 months of DAPT (2.0% vs. 3.4%, HR 0.36, 95% CI 0.36-0.92; P = 0.02). This was somewhat mediated in a 90-day critical badysis (HR 0.59, 95% CI 0.34-1.01; P = 0.053).

All prespecified subgroups appeared to consistently benefit from DAPT regimens, although patients receiving prasugrel or ticagrelor as an inhibitor of P2Y12 versus clopidogrel tended to be more successful after 12 months of DAPT.

"Our study suggests that P2Y12 inhibitor monotherapy after a short duration of DAPT is a new antiplatelet strategy balancing the ischemic and hemorrhagic risk in patients undergoing PCI," Hahn concluded. One of the recognized limitations of the study was that about 16% of patients randomized to monotherapy continued to take aspirin beyond 3 months.

The question of non-respondents to clopidogrel

Roxana Mehran, MD (Icahn School of Medicine at Mount Sinai, New York, NY), who moderated the press conference, commented that the population in these two studies was mixed, with a relatively simple population of patients, Just More than half of SMART CHOICE patients had ACS and only 38% of STOPDAPT-2. "We can not say that everyone is the same size," she said, pointing out that the way in which ICH is carried out in Japan and Korea is not necessarily the same as it is. ;elsewhere.

She was concerned about continuing clopidogrel monotherapy in complex patients, she added. "One of the reasons we do not fear this is the large variance of the CYP2C19 carrier gene that could [lead some patients to be] do not respond, and you basically send a patient home on nothing, "said Mehran.