Key Points
- After DES placement, guidelines recommend considering shorter DAPT duration (e.g. 1-3 months) for those with high bleeding risk (HBR) and longer DAPT duration (e.g., 3-12 months) for those with low-bleeding risk (LBR). However, there is no randomized evidence comparing DAPT duration by bleeding risk category.
- HOST-BR is the first study to stratify patients by bleeding risk and then randomize them to different DAPT durations.
- Approximately ~1600 HBR patients were randomized to either 1 or 3 months of DAPT, and ~3300 LBR patients were randomized to either 3 or 12 months of DAPT after DES placement. The co-primary, hierarchical endpoints were net adverse clinical events (NACE; a composite of all-cause death, MI, stent thrombosis, stroke, or major bleeding), major adverse cardiac or cerebral events (MACCE), and bleeding at 12 months.
- Among HBR patients, a DAPT duration of 1 month was inferior to 3 months for both NACE and MAACE, without a significant improvement in bleeding. Among LBR patients, a DAPT duration of 3 months reduced bleeding compared with 12 months of DAPT, without increasing NACE or MAACE.
- Therefore, 3 months of DAPT appeared to be the optimal duration for both low- and high- bleeding risk populations after PCI with DES. Limitations include generalizability beyond South Korea, as clopidogrel is preferentially used over ticagrelor in this population.
Bleeding risk is a major factor when deciding dual anti-platelet therapy (DAPT) duration after percutaneous coronary intervention (PCI) with drug eluding stent (DES) placement. However, randomized evidence comparing different DAPT durations among those with low- or high-bleeding risk is lacking.
On March 29th 2025, results from “HOST-BR RCT: A Stratified Randomization Study To Compare Different Duration Of Dual Antiplatelet Therapy After Coronary Stenting In Either High Or Low Bleeding Risk Population” were presented at the ACC Scientific Sessions 2025.
HOST-BR was an investigator-initiated, randomized, open-label, multicenter trial sponsored by Seoul National University Hospital and performed in South Korea. It is the first study to stratify patients by bleeding risk and then test different durations of DAPT based on bleeding risk. High bleeding risk (HBR) was defined as a one-year risk of major bleeding ≥4% based on the Academic Research Consortium for High Bleeding Risk (ARC-HBR) score. The study included adults aged ≥19 years who underwent PCI with Xience or Onyx DES for either stable coronary artery disease (CAD) or an acute coronary syndrome.
Those in the HBR stratum were randomized to a 1-month or 3-month DAPT duration and those in the LBR stratum were randomized to a 3-month or 12-month DAPT duration. Three co-primary endpoints were assessed in hierarchical order: net adverse clinical events (NACE: all-cause mortality, myocardial infarction [MI], stent thrombosis, stroke, or major bleeding), major adverse cardiac or cerebral events (MACCE: cardiovascular death, MI, stent thrombosis, ischemic stroke), and bleeding (BARC bleeding 2,3, or 5) at 12 months. The researchers hypothesized that within each bleeding risk stratum, shorter DAPT would be non-inferior to longer DAPT for NACE and MACCE and superior for bleeding. Overall, 1598 HBR and 3299 LBR patients were enrolled, ~99% completed the study with cross-over rates ranging from 5-10%.
The investigator-initiated multicenter study enrolled nearly 4,900 patients in South Korea, one-third (1,598) with HBR and two-thirds (3,299) with LBR. The HBR group was randomized to either one month (n=798) or three months (n=800) of DAPT while the LBR group was randomized to three (n=1649) or 12 months (n=1650) of DAPT. Use of a P2Y12 inhibitor either during the DAPT period or as a monotherapy agent after DAPT was left to clinician discretion. Among HBR patients, the mean age was 73.8 years, 34% were female, 41% had stable CAD, 28% unstable angina, 25% NSTEMI, and 5% STEMI; 90% were discharged on clopidogrel, 6% on ticagrelor, and 1% on prasugrel, and 17% were also discharged on oral anticoagulation. At 1 year, NACE rates were higher in the 1-month DAPT arm compared to the 3-month DAPT arm (18.4% vs. 14.0%HR 1.34 [95% CI: 1.04, 1.71]; p=0.02). Therefore, 1 month of DAPT was not non-inferior to 3-months of DAPT (p for non-inferiority = 0.8). Similarly, 1 month of DAPT was associated with a higher risk of MACCE than 3 months of DAPT (9.8% vs. 5.8%; HR 1.72 [CI: 1.19, 2.50], p=0.004, p for non-inferiority = 1). Finally, there was no significant difference in bleeding between the two arms (1-month: 13.8% vs 3-month: 15.8%; HR 0.85 [CI: 0.66, 1.11], p=0.2). Therefore, for HBR patients after DES, 1 month of DAPT was inferior to 3 months of DAPT for NACE and MAACE, with no observed benefit in terms of bleeding.
Among LBR patients, mean age was 63.2 years, 21% were female, 37% had stable CAD, 31% unstable angina, 19% NSTEMI, and 11% STEMI; 76% were discharged on clopidogrel, 13% on ticagrelor, and 11% on prasugrel, and none were on oral anticoagulation. At 1 year, rates of NACE were significantly lower in the 3-month DAPT group compared to 12-month DAPT group (2.9% vs 4.4%; HR 0.66 [95% CI: 0.46, 0.95]; p=0.03, p for non-inferiority <0.001). MAACE occurred in 2.2% of the 3-month DAPT group and 2.3% of the 12-month DAPT group, a non-significant difference (HR 0.98 [CI: 0.62, 1.56], p=0.95, p for non-inferiority = 0.008). Finally, bleeding was significantly lower in the 3-month DAPT group compared to the 12-month DAPT group (7.4% vs 11.7%; HR 0.63 [CI: 0.50, 0.79], p<0.001). Therefore, for LBR patients after DES, 3 months of DAPT was non-inferior to 12 months of DAPT for NACE and MAACE, and was superior in terms of bleeding.
Limitations include the open-label design and the fact that P2Y12 inhibitor type was left to the discretion of the treating physician. Because this study was done in South Korea, clopidogrel was the dominant P2Y12 inhibitor, as prior evidence suggests clopidogrel is superior to ticagrelor in the East Asian population. Most Western based RCTs, however, have favored ticagrelor, limiting the generalizability of this study to different populations.
Hyo-Soo Kim, MD, PhD, a professor of internal medicine at Seoul National University Hospital in South Korea and the study’s principal investigator, concluded: “Ours is the first study to examine the question of the optimal DAPT duration in patients at both high and low risk of bleeding…Patients with high bleeding risk who received three months of DAPT experienced fewer deaths, heart attacks, blood clots in stents and strokes, with no increase in bleeding episodes, than patients who received one month of dual antiplatelet therapy. For patients with low bleeding risk, three months of dual antiplatelet therapy resulted in similar rates of adverse events and significantly fewer bleeding events compared with 12 months of therapy… Overall, 3 months would be the optimal duration of DAPT after PCI in general to meet the balance of thrombosis/bleeding.”