Dropping Aspirin: Two Trials Explore P2Y12 Monotherapy After Short-term DAPT Post-PCI
The findings may change the paradigm of post-PCI antiplatelet therapy in noncomplex patients, hint STOPDAPT-2 and SMART-CHOICE.
NEW ORLEANS, LA—Two new trials indicate that short-term dual antiplatelet therapy (DAPT) followed by P2Y12-inhibitor monotherapy may provide more of a benefit than 12 months of DAPT among certain PCI patients receiving current-generation DES.
“[These two studies] are really going to change what we do in terms of changing the paradigm from ‘How soon can you stop the P2Y12 inhibitor?’ to ‘How soon can you stop the aspirin?’” said Claire Duvernoy, MD (University of Michigan, Ann Arbor), discussing the two studies in a media briefing here today at the American College of Cardiology (ACC) 2019 Scientific Session. “That's a big shift in what we do.”
Additionally, she added, both the STOPDAPT-2 and SMART-CHOICE trials demonstrate that “second-generation stents are awesome and that they are so much more forgiving than the first-generation stents, where we had these rates of subacute stent thrombosis that were not insignificant and that scared all of us into continuing dual antiplatelet therapy for extended periods of time. That doesn't seem to be necessary, but changing what we give as monotherapy does seem to be the important point here.”
For the STOPDAPT-2 trial, Hirotoshi Watanabe, MD, PhD (Kyoto University Hospital, Japan), who presented the findings, and colleagues enrolled 3,045 patients who received PCI with a cobalt-chromium everolimus-eluting stent (EES; Xience; Abbott) at 90 Japanese centers between December 2015 and December 2017. All patients received DAPT for 1 month (clopidogrel or prasugrel and aspirin), at which point they were randomized to continue on either clopidogrel monotherapy or DAPT with clopidogrel and aspirin through 1 year. Notably, more than 97% of all patients received IVUS- or OCT-guided PCI.
Clopidogrel monotherapy was superior to 12 months of DAPT with regard to the primary endpoint of net adverse cardiovascular events (NACE; composite of cardiovascular death, MI, definite stent thrombosis, stroke, or TIMI major/minor bleeding; 2.4% vs 3.7%; P for superiority = 0.04) and the secondary endpoint of TIMI major/minor bleeding (0.04% vs 1.5%; P for superiority = 0.004). Additionally, clopidogrel monotherapy was noninferior to extended DAPT in terms of the major secondary ischemic endpoint (composite of cardiovascular death, MI, definite stent thrombosis, or stroke; 2.0% vs 2.5%; P for noninferiority = 0.005).
Adverse event rates at 1 year were similar between the study arms, with very low definite and probable stent thrombosis rates overall.
Subgroup analyses showed similar outcomes, with the exception of patients with severe CKD who fared better with 12 months of DAPT.
“One-month DAPT followed by clopidogrel monotherapy provided a net clinical benefit for ischemic and bleeding events over 12-month DAPT with aspirin and clopidogrel after cobalt chromium EES implantation,” Watanabe said. “The benefit was driven by a significant reduction in bleeding events without an increase in ischemic events.”
Session panelist Sunil Rao, MD (Duke Clinical Research Institute, Durham, NC), congratulated the authors “on this very important study” and commented that the results “speak to the evolution of PCI and the safety of DES. It's an interesting design where you power the trial for noninferiority for the MACE endpoint. Traditional approaches would have been to power for noninferiority on the ischemic endpoint and superiority on the bleeding endpoint because we know that shorter durations of DAPT is associated with less bleeding.”
Also, session co-moderator Martin Leon, MD (NewYork-Presbyterian/Columbia University Irving Medical Center, New York, NY), said, “It’s important to note that intravascular imaging was almost uniform in this study, near 100%, which is extraordinary, which is the standard in Japan now. So the very low event rates may be in part related to the intravascular imaging, which could mask a protective pharmacotherapy effect that we're not seeing. It's interesting in terms of generalizability globally.”
In the SMART-CHOICE study, which was presented in the same late-breaking trials session by Joo-Yong Hahn, MD, PhD (Samsung Medical Center, Seoul, Korea), 2,993 patients receiving PCI with current-generation DES (Xience, Promus, Synergy, and Orsiro) at 33 Korean centers were randomized to keep or drop the aspirin after 3 months of DAPT and followed through 1 year.
There was no difference between the short- and long-term DAPT patients regarding the primary endpoint of MACCE (all-cause death, MI, or stroke; 2.9% vs 2.5%; HR 1.19; 95% CI 0.76-1.85), and this was confirmed in a landmark analysis at 90 days.
Clinical outcomes at 12 months were similar between the study groups, with the exception of a greater degree of BARC 2-5 bleeding observed 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 landmark analysis at 90 days (HR 0.59; 95% CI 0.34-1.01; P = 0.053).
All prespecified subgroups seemed to consistently benefit from either DAPT regimens, although patients who received prasugrel or ticagrelor as their P2Y12 inhibitor compared with clopidogrel tended to do better with 12 months of DAPT.
“Our trial suggests that P2Y12 inhibitor monotherapy after short duration of DAPT is a novel antiplatelet strategy balancing ischemic and bleeding risk in patients undergoing PCI,” Hahn concluded. One of the acknowledged limitations of the study was that roughly 16% of patients randomized to monotherapy actually did continue taking aspirin beyond 3 months.
The Issue of Clopidogrel Nonresponders
Roxana Mehran, MD (Icahn School of Medicine at Mount Sinai, New York, NY), who moderated the media briefing, commented on the fact that the population in both of these studies was mixed, with a relatively “simple patient population,” Just over half of the patients in SMART CHOICE had ACS, and just 38% in STOPDAPT-2. “We cannot say one-size-fits-all for everyone,” she said, making the additional point that the way PCI is performed in Japan and Korea is not necessarily the way it is done elsewhere.
She would have concerns moving ahead with clopidogrel monotherapy in complex patients, she added. “One of the reasons why we’d be nervous about doing that is the high variance of the CYP2C19 carrier gene that could [lead some patients to be] nonresponsive, and you're basically sending a patient home on nothing,” Mehran said.
Watanabe H. One-month dual antiplatelet therapy followed by clopidogrel monotherapy versus standard 12-month dual antiplatelet therapy with clopidogrel after drug-eluting stent implantation: STOPDAPT-2 trial. Presented at: ACC 2019. March 18, 2019. New Orleans, LA.
Hahn J-Y. P2Y12 inhibitor monotherapy versus dual antiplatelet therapy in patients undergoing percutaneous coronary intervention: the SMART-CHOICE randomized, open-label, noninferiority trial. Presented at: ACC 2019. March 18, 2019. New Orleans, LA.
- SMART-CHOICE was sponsored by the Korean Society of Interventional Cardiology, Abbott Vascular, Biotronik, and Boston Scientific.
- Watanabe reports no relevant conflicts of interest.
- Hahn reports receiving consulting fees/honoraria from AstraZeneca, Daiichi Sankyo, and Sanofi-Aventis; and research grants from Abbott Korea, Biotronik, Boston Scientific Korea, and Medtronic Korea.