The Consideration of Antiplatelet Therapy in Patients Undergoing DES Implantation from the STOPDAPT-2 ACS Study

We asked Dr. Hirotoshi Watanabe of Kyoto University, who conducted the study, about the optimal DAPT period for ACS patients based on these results and the clinical significance of this study.

Please share with us your honest assessment of these results. Are they different to what you expected?

This study employed a hierarchical test, and we had originally hoped to achieve non-inferiority of the primary endpoint, followed by non-inferiority of the combined cardiovascular endpoint, superiority of the bleeding endpoint, and superiority of the primary endpoint. The results ended up different from our expectations because the first non-inferiority test wasn’t met.

There was a trend of increased cardiovascular events in the 1-month DAPT group. What are your thoughts on this point?

Out of all the studies that examined P2Y12 inhibitors after short-term DAPT, the TICO study that enrolled only ACS patients used ticagrelor monotherapy after 3 months of DAPT. It’s possible that the difference between ticagrelor and clopidogrel, or between 1-month DAPT and 3-month DAPT, may have been what affected the results of the STOPDAPT-2 ACS study.

However, in the GLOBAL LEADERS study that examined ticagrelor monotherapy after 1 month of DAPT, the ACS subanalysis did not show any trend toward increased cardiovascular events, suggesting that differences in P2Y12 inhibitors may be a factor rather than DAPT duration.

If we look at it in terms of the breakdown of cardiovascular events, the rate of myocardial infarction was particularly high in the 1-month DAPT group, but some of these only consisted of cases of troponin elevation. The rate of major infarction with a peak CKMB of 10 times or over the upper limit of normal was not significantly different between the two groups.

How long do you think is the appropriate duration of DAPT after ACS?

From the results of this study, one month is too short a duration for general ACS patients. If the patient is able to take the medication for 12 months, then it should be continued. However, in the ACS subgroup of GLOBAL LEADERS there was no obvious sign of increase in ischemic events after switching to ticagrelor monotherapy after one month. But it must be noted that the GLOBAL LEADERS study did not include a category for ACS patients only.

To reiterate, this answer applies to ACS patients in general and I think it would be different in patients with a high bleeding risk (HBR). The MASTERDAPT presented at ESC 2021 was a study that collected HBR patients, 50% of which were also ACS patients. However, the antiplatelet drug monotherapy after 1-month DAPT did not increase ischemic events, and more than half of those monotherapy consisted of clopidogrel.

I was asked by one of the audience members how to comprehend STOPDAPT-2 ACS, and I think the difference lies in patient background. The subgroup analysis of MASTER DAPT did not show any adverse effects in ACS patients, and clopidogrel monotherapy after 1-month DAPT is considered acceptable for ACS patients on HBR.

Can the results of the study vary depending on the type of DES used? For example, biodegradable polymer vs. durable polymer?

Although the MASTER DAPT is a biodegradable polymer stent and the STOPDAPT-2 ACS is a durable polymer stent with limited use, we do not believe that the differences in polymer are what produced the differences in the results.

Please tell us the clinical significance of this study and what message would you like to convey.

Although the results of this study were different from what we expected, I think it highlights the fact that the risk of ischemic events in ACS patients cannot be ignored in the trend toward shorter DAPT periods. Nevertheless, the data has shown that if it’s between an ischemic risk and a hemorrhagic risk, the hemorrhagic risk takes precedence, and I do not believe that short-term DAPT has been completely ruled out. The optimal regimen for ACS patients who are not at high risk of bleeding in general is a subject for further study.