I'm Hyo-Soo Kim—HS Kim— from Seoul National University Hospital, Korea. I'd like to do a briefing regarding the result of HOST-BR (bleeding risk) RCT where we try to define the optimal duration of DAPT after PCI according to the bleeding risk.

What was the study design, patient population and endpoints?

HOST-BR RCT is the first stratified, randomised clinical trial. We enrolled about 5,000 patients and first stratified them into high bleeding stratum versus low bleeding stratum based on the ARC HBR definition. In previous several clinical trial tested one-month DAPT in patients who require short DAPT period. They are called as HPR trial, but those trials did not use ARC HBR definition in enrolment. This is the first trial to enrol 100% that is defined by ARC definition. Thus we checked three co-primary endpoints that is analysed hierarchical order.

The first component of co-primary endpoint is NACE— net adverse cardiovascular event. Second component is MACE—major adverse cardiocerebral event. The third component is BARC 235 bleeding: any actionable bleeding. Thus, we checked non-inferiority of short DAPT to long DAPT for the first component NACE then MACE. In final component, we try to confirm the superiority of short DAPT to longer DAPT. That is our design of study and co-primary endpoint.

What are the key outcomes?

There's outcomes of high bleeding risk stratum. The first component NACE was higher in one-month DAPT group than three-month DAPT group. It did not meet non-inferiority. The second component was one-year MACE; that was also a little bit higher after one month DAPT then three-month DAPT. The third component, any actionable bleeding was compatible between one-month DAPT and three-month DAPT.

The primary endpoints in low BR stratum: the first component one-year NACE was compatible between two groups. Thus, non-inferiority was met. Thus, we move on the non- inferiority test for the second component, MACE. One-year MACE was also compatible between three-month versus 12-month DAPT. Thus, non-inferiority was met.

Regarding MACCE for one year, the third component we proceed to superiority test. Three-month DAPT was superior to 12-month DAPT in terms of any actionable bleeding. Thus in conclusion, in high bleeding risk stratum three-month DAPT did not meet non-inferiority. One-month DAPT did not meet non- inferiority to three-months DAPT. One-month DAPT was actually inferior to three month in terms of NACE and MACE for one year.

While there is no significant difference in terms of actionable any bleeding, for low BR stratum, three-month DAPT was non-inferior to 12- month DAPT in terms of NACE and MACE while it was superior to 12-month DAPT in terms of any actionable bleeding.

Thus overall, three-month DAPT would be the optimal default duration of DAPT after PCI in general, regardless of bleeding risk, to meet the balance of thrombosis and bleeding.

How should these findings influence clinical decision making?

Current guidelines recommend one to three-month DAPT for high BR and three to 12 month DAPT for low BR. Somebody can say what's the difference one-month versus three- month DAPT, but I don't think it is a trivial issue because the HOST-BR RCT, the high BR stratum in this trial is really brittle, vulnerable, very severe, risky population.

When you check the bleeding instance of high BR, that was sixfold higher than low BR stratum— not only bleeding but also thrombosis is very high. MACE rate is about fourfold higher in high BR stratum than low BR stratum. In other words, high BR population is very tricky and vulnerable, very subtle, friable patients. Thus, I think one versus three- month DAPT may matter.

Luckily, we found optimal duration of DAPT for this brittle population in this trial. I think three-month DAPT would be the sweet spot to meet balance of bleeding and thrombosis. When we shorten durational DAPT toward one month we may lose the prevention of thrombotic event while we cannot get sufficient benefit by reducing major bleeding.

If we extend the duration of DAPT toward six months, we have to pay the tax of bleeding, increase of bleeding without any incremental benefit from the protection against thrombosis like MASTER DAPT trial. They compared one verse six-month DAPT. The conclusion was six-month DAPT did not protect thrombotic event anymore compared with one month DAPT and increased bleeding. Thus I think, once again, three- month DAPT would be the sweet spot of DAPT for PCI patients, not only in high BR but also in non-high BR, low BR, population.

What are the next steps for further research in this area?

The main medication used in our clinical trial is clopidogrel because this is performed in East Asian patients. Most physicians will acknowledge that a recent RCT of ACS and AMI enrolling stations demonstrate clopidogrel DAPT was superior to ticagrelor DAPT, leading to clopidogrel DAPT as a standard and most frequently used regimen. Whereas ticagrelor DAPT was recommended for ACS in the Western world by guidelines. Thus, Western world physicians cannot accept this message, but I think the optimal duration of three months of clopidogrel DAPT for East Asians may be applicable to the duration of ticagrelor DAPT in Western people.

This is very important topic for the future research. Most physicians in the Western world have to do such kind of future research to find optimal duration of ticagrelor DAPT for HBR patients for white or black people.