OPT-CAD Score GUIded Dual ANtiplatelet De-esCalation Time

Official title

OPT-CAD Score Guided Dual Antiplatelet De-escalation Time in Patients With Acute Coronary Syndrome Undergoing Undergoing Percutaneous Coronary Intervention: a Register-based Randomized Controlled Study

Overview

Monotherapy with a P2Y12 inhibitor after a minimum period of DAPT following percutaneous coronary intervention (PCI) is an emerging de-escalation antiplatelet strategy in recent years. However, the optimal timing for de-escalating DAPT in ACS patients undergoing PCI remains debated. The OPT-CAD score is a risk stratification tool derived from Chinese patients which has been demonstrated superior predictive capabilities for ischemic events and all-cause mortality than the GRACE score. Therefore, we hypothesize that the OPT-CAD score can be used to guide the timing of the DAPT de-escalation strategy to monotherapy with P2Y12 inhibitors for ACS patients, that is, low-risk patients could be de-escalated after 1 month, while high-risk patients could be de-escalated after 3 months, so as to achieve individualized antithrombotic therapy and maximize patient benefit.

Detailed description

Antiplatelet therapy is a cornerstone of secondary prevention in patients with coronary artery disease. However, as the use of more potent antithrombotic therapy, it not only lowers ischemic risk but increases bleeding. Therefore, fully balancing the risks of thrombosis and bleeding to maximize patient benefit is the basis for antiplatelet therapy. Although there are several scoring systems to assess the risk of thrombotic or bleeding, such as GRACE score, CRUSADE score, PARIS score, and ARC-HBR criteria, the value of the above scoring systems from western populations in guiding dual antiplatelet therapy (DAPT) decisions has not been confirmed. The previous guidelines recommend considering the PRECISE-DAPT score and DAPT score to guide DAPT duration, but their practical application remains limited. The 2020 ESC NSTE-ACS guidelines pointed out that there is still a gap between evidence and practice regarding whether risk-stratified treatment strategies can improve the prognosis of patients, which urgently requires randomized controlled trials (RCTs) for validation.

Monotherapy with a P2Y12 inhibitor after a minimum period of DAPT following percutaneous coronary intervention (PCI) is an emerging de-escalation strategy DAPT in recent years. Previous RCTs such as STOPDAPT-2, SMART-CHOICE, TICO, and TWILIGHT have demonstrated that compared with the conventional 12-month DAPT regimen, de-escalation of DAPT reduced the risk of bleeding without a significant increase in ischaemic events. To be specific, the intervention groups switched to ticagrelor monotherapy after 3 months of DAPT, resulting in comparable ischemic event rates among both TICO trial enrolled ACS patients undergoing PCI and TWILIGHT trial enrolled high-risk patients undergoing PCI. Meanwhile, when STOPDAPT-2 trial enrolled low-risk patients undergoing PCI, the results also indicated that clopidogrel monotherapy after 1 month of DAPT results in similar thrombotic event risks. However, when STOPDAPT-2 ACS trial enrolled ACS patients, compared to the 12-month DAPT group, the results showed that switching from 1- to 2-month DAPT to clopidogrel monotherapy resulted in an increased incidence of myocardial infarction. Given these findings, the optimal timing for de-escalation of DAPT in ACS patients undergoing PCI remain debated.

The Optimal antiPlatelet Therapy for Chinese patients with Coronary Artery Disease (OPT-CAD) score, a risk stratification tool derived from a real-world, multicenter registration study of Chinese patients, has better predictive performance for ischemic events and all-cause mortality at 1-year than those of The Global Acute Coronary Event Registration (GRACE) score. Through the analysis of OPT-CAD population, it was found that low-risk and medium-high risk patients with OPT-CAD scores accounted for about 2/3 and 1/3, respectively, and the risk of major adverse cardiovascular events (MACE) in medium-high risk patients at 1 year follow-up was about 3 times that of low-risk patients. Therefore, we hypothesize that the OPT-CAD score can be used to guide the timing of DAPT de-escalation strategy to monotherapy with P2Y12 inhibitors for ACS patients, that is, low-risk patients could be de-escalated after 1 month, while high-risk patients could be de-escalated after 3 months, so as to achieve individualized antithrombotic therapy and maximize patient benefit.

Interventions

• Drug standard DAPT
  standard DAPT with aspirin and a P2Y12 inhibitor for 12 months after DES implantation.
• Drug OPT-CAD score guided DAPT de-escalation
  De-escalation DAPT at 3 months for moderate to high risk patients and de-escalation DAPT at 1 month for low risk patients.

Primary outcome measures

• Net adverse clinical events (NACE) [Time frame: 12 months]

Secondary outcome measures (5)

• BARC type 2,3, or 5 bleeding [Time frame: 3 months and 12 months]
• BARC type 3 or 5 bleeding [Time frame: 3 months and 12 months]
• Major adverse cardiac and cerebral events (MACE) [Time frame: 3 months and 12 months]
• All cause death [Time frame: 3 months and 12 months]
• Stent thrombosis [Time frame: 3 months and 12 months]

Eligibility criteria

Inclusion criteria

• Adult patients with ages of 18-80 years;
• Patients with clinically diagnosed ACS who have undergone at least one DES implantation;
• Individuals capable of completing the OPT-CAD scoring calculation;
• Researchers assessing that participants can tolerate at least a 12-month duration of DAPT therapy;
• Written informed consent provided.

Exclusion criteria

• Left main coronary artery lesion PCI;
• Allergy to study drugs such as aspirin, clopidogrel, or ticagrelor;
• Meeting 1 major or 2 minor criteria for high bleeding risk according to the ARC-HBR criteria;
• Anticipated need for revascularization or surgical intervention within 12 months;
• Severe ischemia or hemorrhage events during the current hospitalization;
• Life expectancy of other serious diseases is less than 1 year;
• Pregnant or women of childbearing age who intend to conceive within 1 year;
• Participation in other clinical trials while still under observation;
• Researchers considering ineligibility for enrollment.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

China · 1 center

• General Hospital of Northern Theater Command — Shenyang

Publications

• Collet JP, Thiele H, Barbato E, Barthelemy O, Bauersachs J, Bhatt DL, Dendale P, Dorobantu M, Edvardsen T, Folliguet T, Gale CP, Gilard M, Jobs A, Juni P, Lambrinou E, Lewis BS, Mehilli J, Meliga E, Merkely B, Mueller C, Roffi M, Rutten FH, Sibbing D, Siontis GCM; ESC Scientific Document Group. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persis PMID 32860058
• Kim BK, Hong SJ, Cho YH, Yun KH, Kim YH, Suh Y, Cho JY, Her AY, Cho S, Jeon DW, Yoo SY, Cho DK, Hong BK, Kwon H, Ahn CM, Shin DH, Nam CM, Kim JS, Ko YG, Choi D, Hong MK, Jang Y; TICO Investigators. Effect of Ticagrelor Monotherapy vs Ticagrelor With Aspirin on Major Bleeding and Cardiovascular Events in Patients With Acute Coronary Syndrome: The TICO Randomized Clinical Trial. JAMA. 2020 Jun 16;32 PMID 32543684
• Mehran R, Baber U, Sharma SK, Cohen DJ, Angiolillo DJ, Briguori C, Cha JY, Collier T, Dangas G, Dudek D, Dzavik V, Escaned J, Gil R, Gurbel P, Hamm CW, Henry T, Huber K, Kastrati A, Kaul U, Kornowski R, Krucoff M, Kunadian V, Marx SO, Mehta SR, Moliterno D, Ohman EM, Oldroyd K, Sardella G, Sartori S, Shlofmitz R, Steg PG, Weisz G, Witzenbichler B, Han YL, Pocock S, Gibson CM. Ticagrelor with or wi PMID 31556978
• Hahn JY, Song YB, Oh JH, Chun WJ, Park YH, Jang WJ, Im ES, Jeong JO, Cho BR, Oh SK, Yun KH, Cho DK, Lee JY, Koh YY, Bae JW, Choi JW, Lee WS, Yoon HJ, Lee SU, Cho JH, Choi WG, Rha SW, Lee JM, Park TK, Yang JH, Choi JH, Choi SH, Lee SH, Gwon HC; SMART-CHOICE Investigators. Effect of P2Y12 Inhibitor Monotherapy vs Dual Antiplatelet Therapy on Cardiovascular Events in Patients Undergoing Percutaneous PMID 31237645
• Watanabe H, Domei T, Morimoto T, Natsuaki M, Shiomi H, Toyota T, Ohya M, Suwa S, Takagi K, Nanasato M, Hata Y, Yagi M, Suematsu N, Yokomatsu T, Takamisawa I, Doi M, Noda T, Okayama H, Seino Y, Tada T, Sakamoto H, Hibi K, Abe M, Kawai K, Nakao K, Ando K, Tanabe K, Ikari Y, Hanaoka KI, Morino Y, Kozuma K, Kadota K, Furukawa Y, Nakagawa Y, Kimura T; STOPDAPT-2 Investigators. Effect of 1-Month Dual An PMID 31237644
• Watanabe H, Morimoto T, Natsuaki M, Yamamoto K, Obayashi Y, Ogita M, Suwa S, Isawa T, Domei T, Yamaji K, Tatsushima S, Watanabe H, Ohya M, Tokuyama H, Tada T, Sakamoto H, Mori H, Suzuki H, Nishikura T, Wakabayashi K, Hibi K, Abe M, Kawai K, Nakao K, Ando K, Tanabe K, Ikari Y, Morino Y, Kadota K, Furukawa Y, Nakagawa Y, Kimura T; STOPDAPT-2 ACS Investigators. Comparison of Clopidogrel Monotherapy A PMID 35234821
• Han Y, Chen J, Qiu M, Li Y, Li J, Feng Y, Qiu J, Meng L, Sun Y, Tao G, Wu Z, Yang C, Guo J, Pu K, Chen S, Wang X. Predicting long-term ischemic events using routine clinical parameters in patients with coronary artery disease: The OPT-CAD risk score. Cardiovasc Ther. 2018 Oct;36(5):e12441. doi: 10.1111/1755-5922.12441. Epub 2018 Jun 28. PMID 29869835
• Li X, Qiu M, Na K, Li Y, Ma S, Qi Z, Li J, Li Y, Han Y. Comparison of the efficacy and safety of ticagrelor and clopidogrel in patients with acute coronary syndrome after risk stratification. Catheter Cardiovasc Interv. 2021 May 1;97 Suppl 2:1032-1039. doi: 10.1002/ccd.29591. Epub 2021 Mar 2. PMID 33650763

Identifiers

NCT: NCT06216821 · OPT-GUIDANCE V1.0

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗