Trials Back Shorter DAPT After Stenting

NEW ORLEANS — Some patients can safely quit aspirin after a brief period of dual antiplatelet therapy (DAPT) following drug-eluting stent (DES) implantation, according to two trials from Japan and Korea presented here.

The trials mark a “paradigm shift,” commented Claire Duvernoy, MD, of Michigan Medicine in Ann Arbor, who was not involved in the studies — from asking when the P2Y12 inhibitor can be stopped to “how soon can we stop the aspirin?”

“And that’s a big shift in what we do,” she said during a press conference at the American College of Cardiology annual meeting where the studies were reported. “Changing what we give as monotherapy does appear to be the important point here.”

STOPDAPT-2

In STOPDAPT-2, patients who had just 1 month of DAPT before switching to clopidogrel (Plavix) monotherapy had a lower risk of combined ischemic and bleeding events at 1 year (2.4% vs 3.7%, HR 0.64, 95% CI 0.42-0.98), meeting both non-inferiority and superiority against controls who stayed on 12 full months of DAPT.

“The benefit was driven by significant reduction in bleeding events without increase in ischemic events,” Hirotoshi Watanabe, MD, of Kyoto University in Japan, told attendees at a late-breaking trials session.

Indeed, looking at ischemic events (combined cardiovascular death, MI, stent thrombosis, and stroke), Watanabe’s team observed no difference between groups (2.0% vs 2.5%, HR 0.79, 95% CI 0.49-1.29), and short DAPT met standard DAPT for non-inferiority.

But for TIMI major and minor bleeding, short DAPT showed clear superiority (0.4% vs 1.5%, HR 0.26, 95% CI 0.11-0.64).

Participants in STOPDAPT-2 were 3,009 Xience DES recipients randomized to 1-month DAPT followed by aspirin continuation (mean age 68.1, 79% men) or 12 full months of DAPT (mean age 69.1, 77% men). Excluded were those who needed oral anticoagulation or had a history of intracranial hemorrhage.

Of note, 97% and 98% of 1- and 12-month DAPT groups, respectively, had intravascular ultrasound or optical coherence tomography for their stenting.

After randomization, the short DAPT group generally stayed off DAPT starting at 30 days, whereas some controls started to switch to monotherapy before the end of a full year — 11.9% had quit DAPT by day 335.

On subgroup analysis, it appeared that patients with severe chronic kidney disease did not do better on 1-month DAPT in the primary endpoint, though Watanabe cautioned that the small number of these patients meant the finding wasn’t conclusive.

Another caveat was that most patients presented with low thrombotic and bleeding risk as determined by their CREDO-Kyoto scores. Just under 40% of the group went in with acute coronary syndrome (ACS).

“What you don’t want to take away is you could shorten the duration of DAPT in ACS patients when you only have [so few] patients with ACS,” commented Roxana Mehran, MD, of The Mount Sinai Hospital in New York City, during the press conference. The trial data showed a numerical advantage for 1-month vs 12-month DAPT in the ACS-positive subgroup (2.88% vs 4.02% with a primary endpoint event) but it failed to reach statistical significance (HR 0.72, 95% CI 0.38-1.36).

SMART-CHOICE

Separately, the SMART-CHOICE trial showed that patients can go 3 months on DAPT before switching to P2Y12 inhibitor monotherapy with no increased risk of adverse events after percutaneous coronary intervention.

Non-inferiority was established for short DAPT in the composite of all-cause death, MI, or stroke at 12 months compared to standard 12-month DAPT (2.9% vs 2.5%, HR 1.19, 95% CI 0.76-1.85). Individual components of that endpoint favored neither group except there were more BARC 2-5 bleeds with longer DAPT (3.4% vs 2.0%, P=0.02), according to Joo-Yong Hahn, MD, PhD, of Samsung Medical Center in Seoul, Korea.

“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 said at the same session here. “The 3-month landmark analysis and per-protocol analysis showed consistent results.”

SMART-CHOICE included just under 3,000 patients receiving current-generation DES devices (Xience, Promus, Synergy, or Orsiro) and discharged with aspirin and a P2Y12 inhibitor (clopidogrel in about three-quarters).

Patients were randomized 1:1 to 3 or 12 months of DAPT. Participants’ age averaged about 65 and about 73% were men.

Hahn cautioned that his group had a wide noninferiority margin for the trial, which also had a lower event rate than expected. Moreover, about 16% of those randomized to stop aspirin at 3 months in fact remained on it more than 5 months. Overall, more than 20% of patients assigned to 3-month DAPT were non-adherent in some way, versus 5% of those in the 12-month DAPT group.

“In general, these [trials] will support and accelerate the trend towards shorter DAPT,” commented James Blankenship, MD, of Geisinger Medical Center in Danville, Pennsylvania. But, he added, there remains a question of “whether longer DAPT” — extending beyond 12 months — “is more efficacious in low-bleeding risk patients compared to 12 months of DAPT,” in terms of ischemic events.