6-month versus 12-month or longer dual antiplatelet therapy after percutaneous coronary intervention in patients with acute coronary syndrome (SMART-DATE): a randomised, open-label, non-inferiority trial

SMART-DATE investigators

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Abstract

Background: Current guidelines recommend dual antiplatelet therapy (DAPT) of aspirin plus a P2Y12 inhibitor for at least 12 months after implantation of drug-eluting stents (DES) in patients with acute coronary syndrome. However, available data about the optimal duration of DAPT in patients with acute coronary syndrome undergoing percutaneous coronary intervention are scant. We aimed to investigate whether a 6-month duration of DAPT would be non-inferior to the conventional 12-month or longer duration of DAPT in this population. Methods: We did a randomised, open-label, non-inferiority trial at 31 centres in South Korea. Patients were eligible if they had unstable angina, non-ST-segment elevation myocardial infarction, or ST-segment elevation myocardial infarction, and underwent percutaneous coronary intervention. Enrolled patients were randomly assigned, via a web-based system by computer-generated block randomisation, to either the 6-month DAPT group or to the 12-month or longer DAPT group, with stratification by site, clinical presentation, and diabetes. Assessors were masked to treatment allocation. The primary endpoint was a composite of all-cause death, myocardial infarction, or stroke at 18 months after the index procedure in the intention-to-treat population. Secondary endpoints were the individual components of the primary endpoint; definite or probable stent thrombosis as defined by the Academic Research Consortium; and Bleeding Academic Research Consortium (BARC) type 2–5 bleeding at 18 months after the index procedure. The primary endpoint was also analysed per protocol. This trial is registered with ClinicalTrials.gov, number NCT01701453. Findings: Between Sept 5, 2012, and Dec 31, 2015, we randomly assigned 2712 patients; 1357 to the 6-month DAPT group and 1355 to the 12-month or longer DAPT group. Clopidogrel was used as a P2Y12 inhibitor for DAPT in 1082 (79·7%) patients in the 6-month DAPT group and in 1109 (81·8%) patients in the 12-month or longer DAPT group. The primary endpoint occurred in 63 patients in the 6-month DAPT group and in 56 patients in the 12-month or longer DAPT group (cumulative event rate 4·7% vs 4·2%; absolute risk difference 0·5%; upper limit of one-sided 95% CI 1·8%; pnon-inferiority=0·03 with a predefined non-inferiority margin of 2·0%). Although all-cause mortality did not differ significantly between the 6-month DAPT group and the 12-month or longer DAPT group (35 [2·6%] patients vs 39 [2·9%]; hazard ratio [HR] 0·90 [95% CI 0·57–1·42]; p=0·90) and neither did stroke (11 [0·8%] patients vs 12 [0·9%]; 0·92 [0·41–2·08]; p=0·84), myocardial infarction occurred more frequently in the 6-month DAPT group than in the 12-month or longer DAPT group (24 [1·8%] patients vs ten [0·8%]; 2·41 [1·15–5·05]; p=0·02). 15 (1·1%) patients had stent thrombosis in the 6-month DAPT group compared with ten (0·7%) in the 12-month or longer DAPT group (HR 1·50 [95% CI 0·68–3·35]; p=0·32). The rate of BARC type 2–5 bleeding was 2·7% (35 patients) in the 6-month DAPT group and 3·9% (51 patients) in the 12-month or longer DAPT group (HR 0·69 [95% CI 0·45–1·05]; p=0·09). Results from the per-protocol analysis were similar to those from the intention-to-treat analysis. Interpretation: The increased risk of myocardial infarction with 6-month DAPT and the wide non-inferiority margin prevent us from concluding that short-term DAPT is safe in patients with acute coronary syndrome undergoing percutaneous coronary intervention with current-generation DES. Prolonged DAPT in patients with acute coronary syndrome without excessive risk of bleeding should remain the standard of care. Funding: Abbott Vascular Korea, Medtronic Vascular Korea, Biosensors Inc, and Dong-A ST.

Original languageEnglish
Pages (from-to)1274-1284
Number of pages11
JournalThe Lancet
Volume391
Issue number10127
DOIs
Publication statusPublished - 2018 Mar 31

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Percutaneous Coronary Intervention
Acute Coronary Syndrome
Group Psychotherapy
Therapeutics
Hemorrhage
Drug-Eluting Stents
clopidogrel
Myocardial Infarction
Korea
Stents
Blood Vessels
Thrombosis
Stroke
Research
Republic of Korea
Intention to Treat Analysis
Unstable Angina
Computer Systems
Biosensing Techniques
Standard of Care

ASJC Scopus subject areas

  • Medicine(all)

Cite this

@article{9bdb5cb6de4c421c8249bcef8246c799,
title = "6-month versus 12-month or longer dual antiplatelet therapy after percutaneous coronary intervention in patients with acute coronary syndrome (SMART-DATE): a randomised, open-label, non-inferiority trial",
abstract = "Background: Current guidelines recommend dual antiplatelet therapy (DAPT) of aspirin plus a P2Y12 inhibitor for at least 12 months after implantation of drug-eluting stents (DES) in patients with acute coronary syndrome. However, available data about the optimal duration of DAPT in patients with acute coronary syndrome undergoing percutaneous coronary intervention are scant. We aimed to investigate whether a 6-month duration of DAPT would be non-inferior to the conventional 12-month or longer duration of DAPT in this population. Methods: We did a randomised, open-label, non-inferiority trial at 31 centres in South Korea. Patients were eligible if they had unstable angina, non-ST-segment elevation myocardial infarction, or ST-segment elevation myocardial infarction, and underwent percutaneous coronary intervention. Enrolled patients were randomly assigned, via a web-based system by computer-generated block randomisation, to either the 6-month DAPT group or to the 12-month or longer DAPT group, with stratification by site, clinical presentation, and diabetes. Assessors were masked to treatment allocation. The primary endpoint was a composite of all-cause death, myocardial infarction, or stroke at 18 months after the index procedure in the intention-to-treat population. Secondary endpoints were the individual components of the primary endpoint; definite or probable stent thrombosis as defined by the Academic Research Consortium; and Bleeding Academic Research Consortium (BARC) type 2–5 bleeding at 18 months after the index procedure. The primary endpoint was also analysed per protocol. This trial is registered with ClinicalTrials.gov, number NCT01701453. Findings: Between Sept 5, 2012, and Dec 31, 2015, we randomly assigned 2712 patients; 1357 to the 6-month DAPT group and 1355 to the 12-month or longer DAPT group. Clopidogrel was used as a P2Y12 inhibitor for DAPT in 1082 (79·7{\%}) patients in the 6-month DAPT group and in 1109 (81·8{\%}) patients in the 12-month or longer DAPT group. The primary endpoint occurred in 63 patients in the 6-month DAPT group and in 56 patients in the 12-month or longer DAPT group (cumulative event rate 4·7{\%} vs 4·2{\%}; absolute risk difference 0·5{\%}; upper limit of one-sided 95{\%} CI 1·8{\%}; pnon-inferiority=0·03 with a predefined non-inferiority margin of 2·0{\%}). Although all-cause mortality did not differ significantly between the 6-month DAPT group and the 12-month or longer DAPT group (35 [2·6{\%}] patients vs 39 [2·9{\%}]; hazard ratio [HR] 0·90 [95{\%} CI 0·57–1·42]; p=0·90) and neither did stroke (11 [0·8{\%}] patients vs 12 [0·9{\%}]; 0·92 [0·41–2·08]; p=0·84), myocardial infarction occurred more frequently in the 6-month DAPT group than in the 12-month or longer DAPT group (24 [1·8{\%}] patients vs ten [0·8{\%}]; 2·41 [1·15–5·05]; p=0·02). 15 (1·1{\%}) patients had stent thrombosis in the 6-month DAPT group compared with ten (0·7{\%}) in the 12-month or longer DAPT group (HR 1·50 [95{\%} CI 0·68–3·35]; p=0·32). The rate of BARC type 2–5 bleeding was 2·7{\%} (35 patients) in the 6-month DAPT group and 3·9{\%} (51 patients) in the 12-month or longer DAPT group (HR 0·69 [95{\%} CI 0·45–1·05]; p=0·09). Results from the per-protocol analysis were similar to those from the intention-to-treat analysis. Interpretation: The increased risk of myocardial infarction with 6-month DAPT and the wide non-inferiority margin prevent us from concluding that short-term DAPT is safe in patients with acute coronary syndrome undergoing percutaneous coronary intervention with current-generation DES. Prolonged DAPT in patients with acute coronary syndrome without excessive risk of bleeding should remain the standard of care. Funding: Abbott Vascular Korea, Medtronic Vascular Korea, Biosensors Inc, and Dong-A ST.",
author = "{SMART-DATE investigators} and Hahn, {Joo Yong} and Song, {Young Bin} and Oh, {Ju Hyeon} and Cho, {Deok Kyu} and Lee, {Jin Bae} and Doh, {Joon Hyung} and Kim, {Sang Hyun} and Jeong, {Jin Ok} and Bae, {Jang Ho} and Kim, {Byung Ok} and Cho, {Jang Hyun} and Suh, {Il Woo} and Kim, {Doo il} and Park, {Hoon Ki} and Park, {Jong Seon} and Choi, {Woong Gil} and Lee, {Wang Soo} and Jihoon Kim and Choi, {Ki Hong} and Park, {Taek Kyu} and Lee, {Joo Myung} and Yang, {Jeong Hoon} and Choi, {Jin Ho} and Choi, {Seung Hyuk} and Gwon, {Hyeon Cheol} and Gwon, {Hyeon Cheol} and Hahn, {Joo Yong} and Song, {Young Bin} and Park, {Taek Kyu} and Lee, {Joo Myung} and Yang, {Jeong Hoon} and Choi, {Jin Ho} and Choi, {Seung Hyuk} and Lee, {Jong Young} and Choi, {Woong Gil} and Bae, {Jang Ho} and Park, {Hun Sik} and Hwang, {Jin Yong} and Hur, {Seung Ho} and Seung-Woon Rha and Cho, {Deok Kyu} and Cho, {Sang Cheol} and Kang, {Won You} and Lim, {Seong Hoon} and Lee, {Jin Bae} and Kim, {Moo Hyun} and Cha, {Kwang Soo} and Choi, {Rak Kyung} and Chae, {In Ho} and Oh, {Ju Hyeon}",
year = "2018",
month = "3",
day = "31",
doi = "10.1016/S0140-6736(18)30493-8",
language = "English",
volume = "391",
pages = "1274--1284",
journal = "The Lancet",
issn = "0140-6736",
publisher = "Elsevier Limited",
number = "10127",

}

TY - JOUR

T1 - 6-month versus 12-month or longer dual antiplatelet therapy after percutaneous coronary intervention in patients with acute coronary syndrome (SMART-DATE)

T2 - a randomised, open-label, non-inferiority trial

AU - SMART-DATE investigators

AU - Hahn, Joo Yong

AU - Song, Young Bin

AU - Oh, Ju Hyeon

AU - Cho, Deok Kyu

AU - Lee, Jin Bae

AU - Doh, Joon Hyung

AU - Kim, Sang Hyun

AU - Jeong, Jin Ok

AU - Bae, Jang Ho

AU - Kim, Byung Ok

AU - Cho, Jang Hyun

AU - Suh, Il Woo

AU - Kim, Doo il

AU - Park, Hoon Ki

AU - Park, Jong Seon

AU - Choi, Woong Gil

AU - Lee, Wang Soo

AU - Kim, Jihoon

AU - Choi, Ki Hong

AU - Park, Taek Kyu

AU - Lee, Joo Myung

AU - Yang, Jeong Hoon

AU - Choi, Jin Ho

AU - Choi, Seung Hyuk

AU - Gwon, Hyeon Cheol

AU - Gwon, Hyeon Cheol

AU - Hahn, Joo Yong

AU - Song, Young Bin

AU - Park, Taek Kyu

AU - Lee, Joo Myung

AU - Yang, Jeong Hoon

AU - Choi, Jin Ho

AU - Choi, Seung Hyuk

AU - Lee, Jong Young

AU - Choi, Woong Gil

AU - Bae, Jang Ho

AU - Park, Hun Sik

AU - Hwang, Jin Yong

AU - Hur, Seung Ho

AU - Rha, Seung-Woon

AU - Cho, Deok Kyu

AU - Cho, Sang Cheol

AU - Kang, Won You

AU - Lim, Seong Hoon

AU - Lee, Jin Bae

AU - Kim, Moo Hyun

AU - Cha, Kwang Soo

AU - Choi, Rak Kyung

AU - Chae, In Ho

AU - Oh, Ju Hyeon

PY - 2018/3/31

Y1 - 2018/3/31

N2 - Background: Current guidelines recommend dual antiplatelet therapy (DAPT) of aspirin plus a P2Y12 inhibitor for at least 12 months after implantation of drug-eluting stents (DES) in patients with acute coronary syndrome. However, available data about the optimal duration of DAPT in patients with acute coronary syndrome undergoing percutaneous coronary intervention are scant. We aimed to investigate whether a 6-month duration of DAPT would be non-inferior to the conventional 12-month or longer duration of DAPT in this population. Methods: We did a randomised, open-label, non-inferiority trial at 31 centres in South Korea. Patients were eligible if they had unstable angina, non-ST-segment elevation myocardial infarction, or ST-segment elevation myocardial infarction, and underwent percutaneous coronary intervention. Enrolled patients were randomly assigned, via a web-based system by computer-generated block randomisation, to either the 6-month DAPT group or to the 12-month or longer DAPT group, with stratification by site, clinical presentation, and diabetes. Assessors were masked to treatment allocation. The primary endpoint was a composite of all-cause death, myocardial infarction, or stroke at 18 months after the index procedure in the intention-to-treat population. Secondary endpoints were the individual components of the primary endpoint; definite or probable stent thrombosis as defined by the Academic Research Consortium; and Bleeding Academic Research Consortium (BARC) type 2–5 bleeding at 18 months after the index procedure. The primary endpoint was also analysed per protocol. This trial is registered with ClinicalTrials.gov, number NCT01701453. Findings: Between Sept 5, 2012, and Dec 31, 2015, we randomly assigned 2712 patients; 1357 to the 6-month DAPT group and 1355 to the 12-month or longer DAPT group. Clopidogrel was used as a P2Y12 inhibitor for DAPT in 1082 (79·7%) patients in the 6-month DAPT group and in 1109 (81·8%) patients in the 12-month or longer DAPT group. The primary endpoint occurred in 63 patients in the 6-month DAPT group and in 56 patients in the 12-month or longer DAPT group (cumulative event rate 4·7% vs 4·2%; absolute risk difference 0·5%; upper limit of one-sided 95% CI 1·8%; pnon-inferiority=0·03 with a predefined non-inferiority margin of 2·0%). Although all-cause mortality did not differ significantly between the 6-month DAPT group and the 12-month or longer DAPT group (35 [2·6%] patients vs 39 [2·9%]; hazard ratio [HR] 0·90 [95% CI 0·57–1·42]; p=0·90) and neither did stroke (11 [0·8%] patients vs 12 [0·9%]; 0·92 [0·41–2·08]; p=0·84), myocardial infarction occurred more frequently in the 6-month DAPT group than in the 12-month or longer DAPT group (24 [1·8%] patients vs ten [0·8%]; 2·41 [1·15–5·05]; p=0·02). 15 (1·1%) patients had stent thrombosis in the 6-month DAPT group compared with ten (0·7%) in the 12-month or longer DAPT group (HR 1·50 [95% CI 0·68–3·35]; p=0·32). The rate of BARC type 2–5 bleeding was 2·7% (35 patients) in the 6-month DAPT group and 3·9% (51 patients) in the 12-month or longer DAPT group (HR 0·69 [95% CI 0·45–1·05]; p=0·09). Results from the per-protocol analysis were similar to those from the intention-to-treat analysis. Interpretation: The increased risk of myocardial infarction with 6-month DAPT and the wide non-inferiority margin prevent us from concluding that short-term DAPT is safe in patients with acute coronary syndrome undergoing percutaneous coronary intervention with current-generation DES. Prolonged DAPT in patients with acute coronary syndrome without excessive risk of bleeding should remain the standard of care. Funding: Abbott Vascular Korea, Medtronic Vascular Korea, Biosensors Inc, and Dong-A ST.

AB - Background: Current guidelines recommend dual antiplatelet therapy (DAPT) of aspirin plus a P2Y12 inhibitor for at least 12 months after implantation of drug-eluting stents (DES) in patients with acute coronary syndrome. However, available data about the optimal duration of DAPT in patients with acute coronary syndrome undergoing percutaneous coronary intervention are scant. We aimed to investigate whether a 6-month duration of DAPT would be non-inferior to the conventional 12-month or longer duration of DAPT in this population. Methods: We did a randomised, open-label, non-inferiority trial at 31 centres in South Korea. Patients were eligible if they had unstable angina, non-ST-segment elevation myocardial infarction, or ST-segment elevation myocardial infarction, and underwent percutaneous coronary intervention. Enrolled patients were randomly assigned, via a web-based system by computer-generated block randomisation, to either the 6-month DAPT group or to the 12-month or longer DAPT group, with stratification by site, clinical presentation, and diabetes. Assessors were masked to treatment allocation. The primary endpoint was a composite of all-cause death, myocardial infarction, or stroke at 18 months after the index procedure in the intention-to-treat population. Secondary endpoints were the individual components of the primary endpoint; definite or probable stent thrombosis as defined by the Academic Research Consortium; and Bleeding Academic Research Consortium (BARC) type 2–5 bleeding at 18 months after the index procedure. The primary endpoint was also analysed per protocol. This trial is registered with ClinicalTrials.gov, number NCT01701453. Findings: Between Sept 5, 2012, and Dec 31, 2015, we randomly assigned 2712 patients; 1357 to the 6-month DAPT group and 1355 to the 12-month or longer DAPT group. Clopidogrel was used as a P2Y12 inhibitor for DAPT in 1082 (79·7%) patients in the 6-month DAPT group and in 1109 (81·8%) patients in the 12-month or longer DAPT group. The primary endpoint occurred in 63 patients in the 6-month DAPT group and in 56 patients in the 12-month or longer DAPT group (cumulative event rate 4·7% vs 4·2%; absolute risk difference 0·5%; upper limit of one-sided 95% CI 1·8%; pnon-inferiority=0·03 with a predefined non-inferiority margin of 2·0%). Although all-cause mortality did not differ significantly between the 6-month DAPT group and the 12-month or longer DAPT group (35 [2·6%] patients vs 39 [2·9%]; hazard ratio [HR] 0·90 [95% CI 0·57–1·42]; p=0·90) and neither did stroke (11 [0·8%] patients vs 12 [0·9%]; 0·92 [0·41–2·08]; p=0·84), myocardial infarction occurred more frequently in the 6-month DAPT group than in the 12-month or longer DAPT group (24 [1·8%] patients vs ten [0·8%]; 2·41 [1·15–5·05]; p=0·02). 15 (1·1%) patients had stent thrombosis in the 6-month DAPT group compared with ten (0·7%) in the 12-month or longer DAPT group (HR 1·50 [95% CI 0·68–3·35]; p=0·32). The rate of BARC type 2–5 bleeding was 2·7% (35 patients) in the 6-month DAPT group and 3·9% (51 patients) in the 12-month or longer DAPT group (HR 0·69 [95% CI 0·45–1·05]; p=0·09). Results from the per-protocol analysis were similar to those from the intention-to-treat analysis. Interpretation: The increased risk of myocardial infarction with 6-month DAPT and the wide non-inferiority margin prevent us from concluding that short-term DAPT is safe in patients with acute coronary syndrome undergoing percutaneous coronary intervention with current-generation DES. Prolonged DAPT in patients with acute coronary syndrome without excessive risk of bleeding should remain the standard of care. Funding: Abbott Vascular Korea, Medtronic Vascular Korea, Biosensors Inc, and Dong-A ST.

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UR - http://www.scopus.com/inward/citedby.url?scp=85043381536&partnerID=8YFLogxK

U2 - 10.1016/S0140-6736(18)30493-8

DO - 10.1016/S0140-6736(18)30493-8

M3 - Article

C2 - 29544699

AN - SCOPUS:85043381536

VL - 391

SP - 1274

EP - 1284

JO - The Lancet

JF - The Lancet

SN - 0140-6736

IS - 10127

ER -