Table 1 Characteristics of included randomized controlled trials

RESET, 2012 [23]

Korea

Prospective, multicenter, open-label, randomized clinical trial

1 year

Patients with a diagnosis of angina or acute MI with more than 50% diameter stenosis

DAPT: 1058

Abbreviated DAPT: 1059

DAPT: 62.4 ± 9.8

Abbreviated DAPT: 62.4 ± 9.4

63.62

3 m DAPT

(Aspirin + Clopidogrel)

12 m DAPT

(Aspirin + Clopidogrel)

DM

ACS

Primary endpoints: A composite of death from cardiovascular cause, MI, stent thrombosis, ischemia-driven target-vessel re- vascularization, or bleeding

Secondary endpoints:: Each component of the primary composite endpoints

3-month DAPT was noninferior to the standard therapy with respect to the occurrence of the primary endpoint

OPTIMIZE, 2013 [24]

Brazil

Multicenter, open-label, active-controlled, noninferiority, randomized clinical trial

1 year

Patients with stable coronary artery disease or history of low-risk ACS undergoing PCI with zotarolimus-eluting stents

DAPT: 1556

Abbreviated DAPT: 1563

DAPT: 61.9 ± 10.6

Abbreviated DAPT: 61.3 ± 10.4

63.28

3 m DAPT

(Aspirin + Clopidogrel)

12 m DAPT

(Aspirin + Clopidogrel)

-

Primary endpoints: NACCE (a composite of all-cause death, MI, stroke, or major bleeding specifically, major bleeding incorporated modified major REPLACE-2 and severe or life-threatening GUSTO)

Secondary endpoints: MACE (a composite of all-cause death, MI, emergent coronary artery bypass graft surgery, or target lesion revascularization), target-lesion and target-vessel revascularization, definite or probable stent thrombosis and any bleeding, which included major bleeding plus bleeding events that did not meet criteria for either major or severe or life-threatening bleeding according to modified major REPLACE-2 and severe or life- threatening GUSTO criteria

3 months of DAPT was noninferior to 12 months for NACCE, without significantly increasing the risk of stent thrombosis

GLOBAL LEADERS, 2018 [28]

Multinational

Multicenter, open-label, randomized superiority trial

2 years

Patients scheduled to undergo PCI for stable coronary artery disease or ACS

DAPT: 7988

Abbreviated DAPT: 7980

DAPT: 64.6 ± 1 0.3

Abbreviated DAPT: 64.5 ± 10.3

76.74

1 m DAPT (Aspirin + Ticagrelor) followed by 23 m Ticagrelor monotherapy

12 m DAPT (Aspirin + Clopidogrel [for patients with stable CAD] or Ticagrelor [for patients with ACS]) followed by 12 m Aspirin monotherapy

GLOBAL LEADERS, GLASS Substudy 2019 [33]

GLOBAL LEADERS, Complex PCI (Serruys, 2019 [34]) GLOBAL LEADERS-BMI (Ono, 2020 [35]) GLOBAL LEADERS, DM-CKD (Gao-2020 [36])

GLOBAL LEADERS-ACS (Vranckx, 2021 [37])

Primary endpoints: A composite of all-cause death or new Q-wave MI

Secondary endpoints: Bleeding events (BARC type 3 or 5), a composite endpoint of all-cause death, new Q-wave MI, or stroke; MI; stroke; target vessel or any revascularization; and definite stent thrombosis

Ticagrelor with aspirin for 1 month, followed by ticagrelor monotherapy for 23 months, did not demonstrate better outcomes compared to 12-month DAPT followed by aspirin monotherapy for another 12 months in preventing all-cause mortality or new Q-wave MI two years after PCI

TWILIGHT, 2019 [32]

Multinational

Multicenter, randomized, double-blind placebo controlled trial

1 year

High-risk patients undergoing PCI with DES who have completed a 3-month coarse of DAPT with aspirin and ticagrelor

DAPT: 3564

Abbreviated DAPT: 3555

DAPT: 65.1 ± 10.4

Abbreviated DAPT: 65.2 ± 10.3

76.14

3 m DAPT (Aspirin + Ticagrelor) followed by 12 m Ticagrelor monotherapy

15 m DAPT (Aspirin + Ticagrelor)

TWILIGHT—ACS (Baber, 2020 [38])

TWILIGHT—Complex PCI (Dangas, 2020 [39])

TWILIGHT -Gender (Vogel, 2021 [40])

TWILIGHT—CKD (Stefanini, 2021 [41])

TWILIGHT—HBR (Escaned, 2021 [42])

TWILIGHT—BMI (Kunadian, 2022 [43])

TWILIGHT—DM/CKD (Dehghani, 2022 [44])

Primary endpoints: Type 2, 3, or 5 BARC bleeding

Secondary endpoints: Composite of all-cause death, nonfatal MI, nonfatal stroke; cardiovascular death, MI, ischemic stroke, definite or probable stent thrombosis, and all bleeding events, adjudicated according to the BARC, TIMI, and GUSTO, ISTH classifications

In high-risk patients undergoing PCI who have completed a 3-month coarse of DAPT, ticagrelor monotherapy resulted in lower incidence of clinically relevant bleeding compared to standard DAPT. While, there was no increased risk of death, MI, or stroke with ticagrelor monotherapy

TICO, 2020 [25]

South Korea

Multicenter, randomized, unblinded trial

1 year

Patients who successful PCI for ACS (ST-elevation myocardial infarction, non-ST- elevation myocardial infarction, or unstable angina)

DAPT: 1529

Abbreviated DAPT: 1527

61

80

3 m DAPT (Aspirin + Ticagrelor) followed by Ticagrelor monotherapy

12 m DAPT (Aspirin + Ticagrelor)

TICO—DM (Yun, 2020 [45])

TICO—Age (Kim, 2021 [46])

TICO—ACS (Lee, 2021 [47])

TICO—HBR (Lee, 2022 [48])

TICO—Gender (Lee, 2023 [49])

TICO—BMI (Kim, 2023 [50])

Primary endpoints: NACE (a composite of major bleeding and adverse cardiac and cerebrovascular events)

Secondary endpoints: major bleeding, MACCE, major or minor bleeding, death, MI, stent thrombosis, stroke, target-vessel revascularization, the composite of cardiac death or MI, and the composite of cardiac death, MI, stent thrombosis, or target-vessel revascularization

Comparing to 12-month DAPT, ticagrelor monotherapy after 3-month DAPT led to a slight yet statistically significant decrease in a composite outcome of major bleeding and cardiovascular events at 1 year

REDUCE, 2021 [26]

Multinational

Prospective, multicenter, open‐ label, randomized, clinical trial

2 years

ACS patients who were treated with the COMBO stent

DAPT: 745

Abbreviated DAPT: 751

60.94 ± 8.92

79.81

3 m DAPT (Aspirin + Prasugrel or Ticagrelor or Clopidogrel) followed by Aspirin monotherapy

12 m DAPT (Aspirin + Prasugrel or Ticagrelor or Clopidogrel)

REDUCE-Gender (Verdoia, 2021 [51])

REDUCE-DM (Vranken, 2022 [52])

Primary endpoints: A composite of all‐cause mortality, MI, stent thrombosis, stroke, target vessel revascularization, and bleeding complications ((BARC II, III, V)

Secondary endpoints:: Cardiovascular death or the individual components of the primary endpoint

ACS patients randomized to a 3-month DAPT strategy had similar outcomes to those on standard 12-month DAPT at a 2-year follow-up, for both ischemic events and bleeding complications, regardless of age (elderly or younger patients)

SMARTCHOICE, 2022 [27]

Korea

Multicenter, randomized, open-label, noninferiority trial

3 years

Patients who had at least 1 stenosis of 50% or greater in a native coronary artery with a visually estimated diameter of 2.25 mm or larger and 4.25 mm or smaller that was suitable for PCI

DAPT: 1498

Abbreviated DAPT: 1495

DAPT: 64.6 ± 10.7

Abbreviated DAPT: 64.6 ± 10.7

73.43

3 m DAPT (Aspirin + Clopidogrel or Prasugrel or Ticagrelor) followed by P2Y12 inhibitor monotherapy

12 m DAPT (Aspirin + Clopidogrel or Prasugrel or Ticagrelor)

SMARTCHOICE -Complex PCI (Roh, 2021 [53])

SMARTCHOICE -Gender (Shin, 2023 [54])

Primary endpoints: MACCE (a composite of all-cause death, MI, or stroke)

Secondary endpoints: The components of the primary endpoint, cardiac death, target-vessel revascularization, any revascularization, stent thrombosis, bleeding (BARC types 2–5), major bleeding (BARC types 3–5), and NACCE (a composite of all-cause death, MI, stroke, and BARC types 2–5 bleeding)

3-month DAPT followed by P2Y12 inhibitor monotherapy significantly decreased the rate of major bleeding over a 3-year follow-up period. However, there was no significant difference in the 3-year risk of ischemic cardiovascular events between the two groups

MASTERDAPT, 2023 [29]

Europe, South America, the Middle East, Asia, and Australia

Multicenter, randomized, open-label, noninferiority trial

15 months

HBR patients with acute or chronic coronary syndromes who underwent PCI

DAPT: 2295

Abbreviated DAPT: 2284

DAPT: 75.86 ± 8.80

Abbreviated DAPT: 76.06 ± 8.73

69.19

1 m DAPT (Aspirin + Clopidogrel or Prasugrel or Ticagrelor) followed by 11 m P2Y12 inhibitor monotherapy

12 m DAPT (Aspirin + Clopidogrel or Prasugrel or Ticagrelor)

Complex PCI (Valgimigli, 2022 [55])

Gender

(Landi, 2024 [56])

Primary endpoints: NACE, MACCE, major or clinically relevant nonmajor bleeding (composite of type 2, 3, or 5 BARC bleeding)

Secondary endpoints: The composite of cardiovascular death, MI, and stroke; The composite of cardiovascular death, MI, definite or probable stent thrombosis, The composite of stroke and transient ischemic attack; and all bleeding events, adjudicated according to the BARC, TIMI, and GUSTO classifications

At 15 months, there was no significant difference in the occurrence of NACE and MACCE between HBR patients who received abbreviated and standard DAPT. However, the risk of major or clinically relevant nonmajor bleeding was lower with abbreviated DAPT compared with standard therapy

T-PASS, 2023 [30]

South Korea

Multicenter, randomized, open-label, noninferiority trial

1 year

Patients with ACS who had undergone DES implantation

DAPT: 1424

Abbreviated DAPT: 1426

61

83.39

 < 1 month of DAPT (Aspirin + Ticagrelor) followed by Ticagrelor monotherapy

12 m DAPT (Aspirin + Ticagrelor)

-

Primary endpoints: A composite of all-cause death, myocardial infarction, stent thrombosis, stroke, and major bleeding

Secondary endpoints: All-cause death, cardiovascular death, MI, stent thrombosis, stroke, major bleeding, minor or major bleeding, and MACE composed of cardiovascular death, myocardial infarction, stent thrombosis, and ischemia-driven target-vessel revascularization

In Patients with ACS who had undergone DES implantation, < 1 month of DAPT followed by ticagrelor monotherapy demonstrated superiority over 12-months DAPT for one-year composite outcome of death, MI, stent thrombosis, stroke, and major bleeding. This superiority was mainly due to a significant reduction in bleeding events

HOSTIDEA, 2023 [11]

South Korea

Multicenter, open-label, noninferiority, adjudicator-blinded randomized clinical trial

1 year

Patients with de novo stenotic lesions and without ST-segment–elevation MI suitable for DES implantation

DAPT: 1011

Abbreviated DAPT: 1002

65.7 ± 10.5

73.9

3 to 6 m DAPT (Aspirin + Clopidogrel or Prasugrel or Ticagrelor) followed by monotherapy

(aspirin or clopidogrel for patients with SIHD; aspirin, clopidogrel, ticagrelor, or prasugrel for patients with ACS)

12 m DAPT

(Aspirin + Clopidogrel or Prasugrel or Ticagrelor)

-

Primary endpoints: NACE, a composite of cardiac death, target vessel MI, clinically driven target lesion revascularization, stent thrombosis, or major bleeding (BARC 3 or 5)

Secondary endpoints: Target lesion failure, a composite of cardiac death, target vessel MI, clinically driven target lesion revascularization, and major bleeding

3- to 6-month DAPT was noninferior to 12-month DAPT for NACE. There were no significant differences in target lesion failure or major bleeding between the 2 groups

STOPDAPT-2, 2024 [31]

Japan

Prospective, multicenter, open-label, adjudicator-blinded randomized clinical trial

5 years

Patients who underwent successful PCI (ACS: 38.3%)

DAPT: 1486

Abbreviated DAPT: 1471

68.6 ± 10.7

77.7

1 m DAPT (Aspirin + Clopidogrel or Prasugrel) followed by Clopidogrel monotherapy

12 m DAPT (1 month Aspirin + Clopidogrel or Prasugrel followed by Aspirin + Clopidogrel)

STOPDAPT- HBR/complex PCI (Watanabe, 2023 [57])

STOPDAPT-2-DM (Yamamoto, 2023 [58])

STOPDAPT-2-ACS (Watanabe, 2022 [10])

Primary endpoints: A composite of cardiovascular outcomes (death from cardiovascular cause, MI, definite stent thrombosis, stroke including both ischemic and hemorrhagic) and bleeding outcomes defined as TIMI major or minor bleeding

Secondary endpoints:

The cardiovascular and bleeding components of the primary endpoint

Clopidogrel monotherapy, compared to the aspirin monotherapy, was found to be non-inferior but not superior for the primary endpoint. However, it demonstrated superiority for cardiovascular outcomes and showed no superiority for major bleeding. In the 1-year landmark analysis, clopidogrel showed a numerical advantage over aspirin for cardiovascular events, though this difference was not statistically significant, and there was no disparity in major bleeding

STOPDAPT-3, 2024 [12]

Japan

Prospective, multicenter, open-label, adjudicator-blinded randomized clinical trial

1 month

Patients with ACS regardless of HBR or non-ACS with HBR with minimal exclusion criteria

DAPT: 2982

No-aspirin: 2984

71.6 ± 11.7

76.6

1 m Prasugrel

1 m DAPT (Aspirin + Prasugrel)

STOPDAPT-3-HBR (Obayashi, 2024 [59])

Primary endpoints: BARC type 3 or 5, a composite of cardiovascular death, MI, definite stent thrombosis, or ischemic stroke

Secondary endpoints: A composite of the coprimary bleeding and cardiovascular end points representing net adverse clinical outcomes

After 1 month, the no-aspirin group did not show superiority over the DAPT group for the primary bleeding endpoint. However, the no-aspirin group was considered noninferior to the DAPT group for the primary cardiovascular endpoint. There were no differences in net adverse clinical outcomes or each component of the primary cardiovascular endpoint between the two groups. However, the no-aspirin group had more cases of unplanned coronary revascularization and subacute definite or probable stent thrombosis compared to the DAPT group