Chinese Registry Supports Prolonged DAPT Following PCI for ACS

Long-term dual antiplatelet therapy (DAPT) reduces ischemic events without a trade-off in bleeding compared with shorter durations among ACS patients who undergo PCI, according to new registry data from China.

The findings, released at the virtual Society for Cardiovascular Angiography and Interventions (SCAI) 2021 meeting, are slightly out of step with the TWILIGHT ACS substudy, which indicated a shorter duration of DAPT followed by ticagrelor monotherapy lowers bleeding risk in these patients without increasing ischemic events. In the Chinese registry, DAPT primarily consisted of clopidogrel and aspirin.

“To the best of our knowledge, this is the first report investigating the feasibility and safety of long-term DAPT for high-risk ‘TWILIGHT-like’ patients with ACS treated with DES,” Hao-Yu Wang, MD (Fuwai Hospital, Beijing, China), said in his presentation. “These results suggested that prolonged DAPT in ACS patients who present with a particularly higher risk for thrombotic complications without excessive risk of bleeding could remain the standard of care.”

Here, Longer Is Better

The study showed that among a population of 4,875 high-risk patients from the prospective Fuwai PCI registry—similar to those enrolled in the TWILIGHT trial, according to trial inclusion criteria—the 68.4% who stayed on DAPT for at least 12 months (mean duration 663 days) saw a lower risk of the composite endpoint of all-cause death, MI, or stroke at 30 months by 63% (1.5% vs 3.8%; adjusted HR 0.37; 95% CI 0.26-0.55) compared with those who stopped DAPT sooner than 12 months. The researchers also found no difference in the combined rates of BARC 2, 3, or 5 bleeding between the study groups (0.9% vs 1.3%; adjusted HR 0.67; 95% CI 0.38-1.18).

Among the 1,540 patients in the short DAPT group (mean duration 350 days), 91.4% stopped clopidogrel before 12 months while 3% stopped aspirin early and 5.6% stopped both drugs. Notably, only 0.2% of the total population was treated with ticagrelor, according to Wang.

In propensity analyses, the individual endpoint of cardiovascular death favored prolonged DAPT (HR 0.05; 95% CI 0.01-0.36), while there were no differences in MI (HR 0.45; 95% CI 0.15-1.32) and definite/probable stent thrombosis (HR 0.30; 95% CI 0.08-1.10). Also, the effect of long-term DAPT was consistent among patients with one to three, four to five, and six to nine risk factors (P < 0.05 for interaction).

Wang said the differences between their results and those of TWILIGHT likely stem from both differences in the patients themselves as well as the fact that most Chinese patients are treated with clopidogrel as the P2Y12 agent of choice for DAPT.

The investigators, in a paper published in Catheterization and Cardiovascular Interventions timed to coincide with SCAI, note that the registry “findings may appear somewhat discordant to the TWILIGHT-ACS substudy.”

But, they write, the MACE risk observed in TWILIGHT-ACS for placebo versus aspirin was not negligible, “particularly in those with more risk factors. Also, TWILIGHT-ACS excluded STEMI patients and generally included lower-risk patients than their registry. “In addition, the findings of TWILIGHT-ACS substudy cannot generalize to patients treated with clopidogrel given that all patients with NSTE-ACS received ticagrelor as P2Y12 inhibitor,” the researchers say.

David Cox, MD (Brookwood Baptist Health, Birmingham AL), in a media briefing ahead of the SCAI session, called the new results “controversial.” However, he said, “it just shows you as science marches on you get these contradictory studies, and you’ve got to balance it all. I still can’t figure out if aspirin is good for our patients or not, and I think we sort of individualize it more and more.”

Clinical Judgement and Risk Stratification

Commenting on the study following its presentation, J. Dawn Abbott, MD (Brown University, Providence, RI), said it is “reminiscent of the randomized prospective DAPT trial because you're taking a population of patients who are event free of bleeding and ischemia at 12 months and then looking at their outcomes.” But instead of being randomized, in the registry the choice to continue DAPT or switch to monotherapy was made on the basis of clinical judgement, she continued. “I suspect it would be very important to look at the interaction with the DAPT Score, because certainly we can identify patients that benefit from that prolonged DAPT.”

Additionally, she called for a standard bleeding risk score—like PRECISE-DAPT or ARC-HBR—to be used in all trials looking at DAPT duration, “because we go from ‘shorter is better’ to ‘longer is better.’ . . . We have to be able to speak the same language,” Abbott said. “Using TWILIGHT criteria is very complicated because the clinical and angiographic criteria are pretty specific to that individual trial. So, I would just advocate looking at some more-standard definitions.”

Session panelist Ron Waksman, MD (MedStar Washington Hospital Center, Washington, DC), said it is important for clinicians “to recognize that not all ACS are the same. It's a very wide spectrum of patients and classification of scoring, so I don't know if this was taken into account.”

Another take-home message would be to “emphasize that clinical judgement in risk-stratifying these patients—both in terms of their ischemic risk up front as well as their bleeding risk up front—really allows us to tailor therapy to the individual patient,” said Bonnie Weiner, MD (Saint Vincent Hospital, Worcester, MA). “I think these data really confirm that patients who are at low bleeding risk actually do well on longer-term antiplatelet therapy and [that] we, for the most part, can identify those folks up front. Purely the drive to shorten dual antiplatelet therapy in and of itself may not be the right answer in all patients.”