Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention

Conditions

Cardiovascular Disease, Interventional Cardiology

Keywords

PCI, DAPT, ticagrelor, aspirin

Brief summary

The purpose of this study is to compare the use of ticagrelor alone versus ticagrelor and aspirin together. Both ticagrelor and aspirin stop platelets from sticking together and forming a blood clot that could block blood flow to the heart. This study will look to determine the effectiveness and safety of ticagrelor alone, compared to ticagrelor plus aspirin in reducing clinically relevant bleeding and in reducing ischemic adverse events among high-risk patients who have had a percutaneous intervention with at least one drug-eluting stent. A patient is considered high-risk if they meet certain clinical and/or anatomic criteria. Up to 9000 subjects will be enrolled at the time of their index PCI. Subjects meeting randomization eligibility criteria at 3 months post enrollment will be randomized to either ticagrelor plus aspirin or ticagrelor plus placebo for an additional 12 months. Follow-up clinic visits will be performed at 3 months, 9 months and 15 months post enrollment.

Detailed description

This is a multicenter, prospective, blinded dual-arm study. Up to 9000 high-risk patients who have undergone successful PCI with at least one locally approved drug eluting stent discharged on DAPT with aspirin and ticagrelor of at least 3 months intended duration from centers still to be determined in the U.S., Canada, Europe and Asia. The primary objective of this study is to determine the impact of antiplatelet monotherapy with ticagrelor alone versus DAPT with ticagrelor plus aspirin for 12 months in reducing clinically relevant bleeding (efficacy) among high-risk patients undergoing PCI who have completed a 3-month course of aspirin plus ticagrelor. The secondary objective of this study is to determine the impact of antiplatelet monotherapy with ticagrelor alone versus DAPT with ticagrelor plus aspirin for 12 months in reducing major ischemic adverse events (safety) among high-risk patients undergoing PCI who have completed a 3-month course of aspirin plus ticagrelor. Exploratory objectives include assessing the comparative safety and efficacy of the different DAPT regimens for individual components of the primary efficacy and secondary safety objectives. The primary analysis for TWILIGHT will be performed independently by the London School of Hygiene and Tropical Medicine

Steg PG, Nicolas J, Baber U, Sartori S, Zhang Z, Feng Y, Angiolillo DJ, Briguori C, Cohen DJ, Collier T, Dangas G, Dudek D, Escaned J, Gibson CM, Han YL, Huber K, Kastrati A, Kaul U, Marx SO, Kornowski R, Kunadian V, Vogel B, Oliva A, Mehta SR, Moliterno D, Sardella G, Krucoff M, Shlofmitz RA, Sharma S, Pocock S, Mehran R.

2025-01-30

10.1016/j.ahj.2025.01.016

Ticagrelor with or without aspirin following percutaneous coronary intervention in high-risk patients with concomitant peripheral artery disease: A subgroup analysis of the TWILIGHT randomized clinical trial.

Krucoff M, Spirito A, Baber U, Sartori S, Angiolillo DJ, Briguori C, Cohen DJ, Collier T, Dangas G, Dudek D, Escaned J, Gibson CM, Han YL, Huber K, Kastrati A, Kaul U, Kornowski R, Kunadian V, Vogel B, Mehta SR, Moliterno D, Sardella G, Shlofmitz RA, Sharma S, Steg PG, Pocock S, Mehran R.

2024-03-06

10.1016/j.ahj.2024.03.002

Clinically Driven Revascularization in High-Risk Patients Treated With Ticagrelor Monotherapy After PCI: Insights from the Randomized TWILIGHT Trial.

Baber U, Spirito A, Sartori S, Angiolillo DJ, Briguori C, Cohen DJ, Collier T, Dangas G, Dudek D, Escaned J, Gibson CM, Han YL, Huber K, Kastrati A, Kaul U, Kornowski R, Krucoff M, Kunadian V, Vogel B, Mehta SR, Moliterno D, Sardella G, Shlofmitz RA, Sharma S, Steg PG, Pocock S, Mehran R.

2023-10-063 citations

10.1016/j.amjcard.2023.09.008

Bleeding and Ischemic Risks of Ticagrelor Monotherapy After Coronary Interventions.

Mendieta G, Mehta S, Baber U, Angiolillo DJ, Briguori C, Cohen D, Collier T, Dangas G, Dudek D, Escaned J, Gil R, Vogel B, Cao D, Spirito A, Huber K, Kastrati A, Kaul U, Kornowski R, Krucoff MW, Kunadian V, Moliterno DJ, Ohman EM, Sardella G, Sartori S, Sharma S, Shlofmitz R, Steg PG, Han YL, Pocock S, Gibson CM, Mehran R.

2023-08-014 citations

10.1016/j.jacc.2023.05.062

Fatal, ischemic and bleeding risk of patients meeting the selection criteria of the TWILIGHT trial: Insights from a large PCI registry.

Spirito A, Koh WJ, Sartori S, Vogel B, Feng Y, Baber U, Nicolas J, Snyder C, Kamaleldin K, Pileggi B, Rezvanizadeh V, Sweeny J, Sharma SK, Kini A, Pocock SJ, Dangas G, Mehran R.

2023-04-231 citations

10.1016/j.ahj.2023.04.007

Ticagrelor with or without aspirin in high-risk patients with anaemia undergoing percutaneous coronary intervention: a subgroup analysis of the TWILIGHT trial

Alessandro Spirito, Adnan Kastrati, Davide Cao, Usman Baber, Samantha Sartori et al. (26 authors)

European Heart Journal - Cardiovascular Pharmacotherapy2023-01-17

10.1093/ehjcvp/pvad006

Ticagrelor With or Without Aspirin in Chinese Patients Undergoing Percutaneous Coronary Intervention: A TWILIGHT China Substudy.

Yaling Han, Bimmer E. Claessen, Shaoliang Chen, Qiu Chunguang, Yujie Zhou et al. (38 authors)

PubMed2022-04-016 citations

10.1161/circinterventions.120.009495

Ticagrelor Monotherapy After PCI in High-Risk Patients With Prior MI: A Prespecified TWILIGHT Substudy.

Chiarito M, Baber U, Cao D, Sharma SK, Dangas G, Angiolillo DJ, Briguori C, Cohen DJ, Dudek D, Džavík V, Escaned J, Gil R, Hamm CW, Henry T, Huber K, Kastrati A, Kaul U, Kornowski R, Krucoff M, Kunadian V, Mehta SR, Moliterno D, Ohman EM, Oldroyd K, Sardella G, Zhongjie Z, Sartori S, Stefanini G, Shlofmitz R, Steg PG, Weisz G, Witzenbichler B, Han YL, Pocock S, Gibson CM, Mehran R.

2022-01-126 citations

10.1016/j.jcin.2021.11.005

Sex Differences Among Patients With High Risk Receiving Ticagrelor With or Without Aspirin After Percutaneous Coronary Intervention

Birgit Vogel, Usman Baber, David J. Cohen, Samantha Sartori, Samin K. Sharma et al. (29 authors)

JAMA Cardiology2021-05-1554 citations

10.1001/jamacardio.2021.1720

Ticagrelor alone vs. ticagrelor plus aspirin following percutaneous coronary intervention in patients with non-ST-segment elevation acute coronary syndromes: TWILIGHT-ACS

Usman Baber, George Dangas, Dominick J. Angiolillo, David J. Cohen, Samin K. Sharma et al. (37 authors)

European Heart Journal2020-08-04166 citations

10.1093/eurheartj/ehaa670

Ticagrelor With or Without Aspirin After Complex PCI.

Dangas G, Baber U, Sharma S, Giustino G, Mehta S, Cohen DJ, Angiolillo DJ, Sartori S, Chandiramani R, Briguori C, Dudek D, Escaned J, Huber K, Collier T, Kornowski R, Kunadian V, Kaul U, Oldroyd K, Sardella G, Shlofmitz R, Witzenbichler B, Ya-Ling H, Pocock S, Gibson CM, Mehran R.

2020-03-30119 citations

10.1016/j.jacc.2020.03.011

Ticagrelor With or Without Aspirin in High-Risk Patients With Diabetes Mellitus Undergoing Percutaneous Coronary Intervention.

Angiolillo DJ, Baber U, Sartori S, Briguori C, Dangas G, Cohen DJ, Mehta SR, Gibson CM, Chandiramani R, Huber K, Kornowski R, Weisz G, Kunadian V, Oldroyd KG, Ya-Ling H, Kaul U, Witzenbichler B, Dudek D, Sardella G, Escaned J, Sharma S, Shlofmitz RA, Collier T, Pocock S, Mehran R.

2020-03-3058 citations

10.1016/j.jacc.2020.03.008

Can Limiting Dual Antiplatelet Therapy to 3 Months Reduce Bleeding

Howard C. Herrmann

Journal watch2019-10-08

10.1056/nejm-jw.na50020

Ticagrelor with or without Aspirin in High-Risk Patients after PCI

Roxana Mehran, Usman Baber, Samin K. Sharma, David J. Cohen, Dominick J. Angiolillo et al. (36 authors)

New England Journal of Medicine2019-09-26956 citations

10.1056/nejmoa1908419

Clinical implementation of rapid CYP2C19 genotyping to guide antiplatelet therapy after percutaneous coronary intervention.

Cavallari LH, Franchi F, Rollini F, Been L, Rivas A, Agarwal M, Smith DM, Newsom K, Gong Y, Elsey AR, Starostik P, Johnson JA, Angiolillo DJ.

2018-04-1147 citations

10.1186/s12967-018-1469-8

Impact of Diabetes Mellitus on the Pharmacodynamic Effects of Ticagrelor Versus Clopidogrel in Troponin‐Negative Acute Coronary Syndrome Patients Undergoing Ad Hoc Percutaneous Coronary Intervention

Joseph Sweeny, Dominick J. Angiolillo, Francesco Franchi, Fabiana Rollini, Ron Waksman et al. (12 authors)

Journal of the American Heart Association2017-03-3038 citations

10.1161/jaha.117.005650

Interventions

DRUGAspirin

DRUGPlacebo

DRUGticagrelor

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

SUPPORTIVE_CARE

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

Inclusion criteria

* High-risk patients who have undergone successful PCI with at least one locally approved drug eluting stent discharged on DAPT with aspirin and ticagrelor of at least 3 months intended duration will be eligible for the TWILIGHT study. * Enrollment into the study will require meeting at least one clinical inclusion, one angiographic inclusion and none of the

Exclusion criteria

. Clinical Inclusion Criteria: * Adult patients ≥ 65 years of age * Female gender * Troponin Positive acute coronary syndrome * Established vascular disease defined as previous MI, documented PAD or CAD/PAD revascularization * Diabetes mellitus treated with medications (oral hypoglycemic, subcutaneous injection of insulin) * Chronic kidney disease defined as an estimated glomerular filtration rate (eGFR) \< 60 ml/min/1.73m2 or creatinine clearance (CrCl) \< 60 ml/min Angiographic Inclusion Criteria: * Multivessel coronary artery disease * Target lesion requiring total stent length \>30 mm * Thrombotic target lesion(s) * Bifurcation lesions with Medina X,1,1 classification requiring at least 2 stents * Left main (≥50%) or proximal LAD (≥70%) lesion * Calcified target lesion(s) requiring atherectomy

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With BARC Type 2, 3, or 5	12 months after randomization	Number of participants with first occurrence of clinically relevant bleeding episode, defined as Bleeding Academic Research Consortium (BARC) Types 2, 3 or 5 bleeding. BARC bleeding types range from 0 (no bleeding) to 5 (fatal bleeding).

Secondary

Measure	Time frame	Description
Number of Participants With Ischemic Episode	12 months after randomization	Number of participants with first occurrence of confirmed all-cause death, non-fatal myocardial infarction or stroke.

Countries

United States

Participant flow

Recruitment details

From July 2015 through December 2017, 9006 patients were enrolled, and 7119 underwent randomization after 3 months

Pre-assignment details

1887 excluded from randomization (106 lost to follow up, 243 had adverse events between enrollment and randomization: a) myocardial infarction, stroke or death, b) revascularizations, and/or c) BARC type 3b or higher bleedings, 1148 were not adherent to DAPT, 267 withdrew consent or declined to participate, and 123 had other reasons.)

Participants by arm

Arm	Count
Placebo + Ticagrelor placebo pill daily p.o. for 12 months - match for enteric coated aspirin 81mg-100mg and ticagrelor 90mg tablet bid for 12 months	3,555
Aspirin + Ticagrelor enteric coated aspirin 81mg-100mg daily p.o. for 12 months and ticagrelor 90mg tablet bid for 12 months	3,564
Total	7,119

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Lost to Follow-up	41	27
Overall Study	Physician Decision	0	1
Overall Study	Withdrawal by Subject	18	25

Baseline characteristics

Characteristic	Placebo + Ticagrelor	Aspirin + Ticagrelor	Total
Age, Continuous	65.2 years STANDARD_DEVIATION 10.3	65.1 years STANDARD_DEVIATION 10.4	65.1 years STANDARD_DEVIATION 10.3
Anemia	675 Participants	654 Participants	1329 Participants
Body Mass Index (BMI)	28.6 kg/m^2 STANDARD_DEVIATION 5.5	28.5 kg/m^2 STANDARD_DEVIATION 5.6	28.6 kg/m^2 STANDARD_DEVIATION 5.6
Chronic Kidney Disease (CKD)	572 Participants	573 Participants	1145 Participants
Current smoker	726 Participants	822 Participants	1548 Participants
Diabetes Mellitus	1319 Participants	1301 Participants	2620 Participants
Diabetes treated with Insulin	335 Participants	374 Participants	709 Participants
Hypercholesterolemia	2157 Participants	2146 Participants	4303 Participants
Hypertension	2580 Participants	2574 Participants	5154 Participants
Indication for PCI Asymptomatic	234 Participants	223 Participants	457 Participants
Indication for PCI NSTEMI (non-ST-segment elevation MI)	1024 Participants	1096 Participants	2120 Participants
Indication for PCI Stable angina	1047 Participants	999 Participants	2046 Participants
Indication for PCI Unstable angina	1249 Participants	1245 Participants	2494 Participants
Multivessel Coronary Artery Disease (CAD)	2272 Participants	2194 Participants	4466 Participants
Peripheral Arterial Disease (PAD)	245 Participants	244 Participants	489 Participants
Previous Coronary Artery Bypass Graft (CABG)	362 Participants	348 Participants	710 Participants
Previous Major Bleeding Event	31 Participants	32 Participants	63 Participants
Previous Myocardial Infarction (MI)	1020 Participants	1020 Participants	2040 Participants
Previous Percutaneous Coronary Intervention (PCI)	1502 Participants	1496 Participants	2998 Participants
Race/Ethnicity, Customized Nonwhite race	1110 Participants	1086 Participants	2196 Participants
Race/Ethnicity, Customized Unknown	2445 Participants	2478 Participants	4923 Participants
Region of Enrollment China	512 Participants	516 Participants	1028 Participants
Region of Enrollment Europe	1251 Participants	1258 Participants	2509 Participants
Region of Enrollment India	308 Participants	302 Participants	610 Participants
Region of Enrollment North America	1484 Participants	1488 Participants	2972 Participants
Sex: Female, Male Female	846 Participants	852 Participants	1698 Participants
Sex: Female, Male Male	2709 Participants	2712 Participants	5421 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	34 / 3,524	45 / 3,515
other Total, other adverse events	0 / 3,555	0 / 3,564
serious Total, serious adverse events	262 / 3,555	370 / 3,564

Outcome results

Primary

Number of Participants With BARC Type 2, 3, or 5

Number of participants with first occurrence of clinically relevant bleeding episode, defined as Bleeding Academic Research Consortium (BARC) Types 2, 3 or 5 bleeding. BARC bleeding types range from 0 (no bleeding) to 5 (fatal bleeding).

Time frame: 12 months after randomization

Population: Data for the intention-to-treat population

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Placebo + Ticagrelor	Number of Participants With BARC Type 2, 3, or 5	141 Participants
Aspirin + Ticagrelor	Number of Participants With BARC Type 2, 3, or 5	250 Participants

Secondary

Number of Participants With Ischemic Episode

Number of participants with first occurrence of confirmed all-cause death, non-fatal myocardial infarction or stroke.

Time frame: 12 months after randomization

Population: data for the per-protocol population , i.e., the participants who underwent randomization and had no major deviations from the protocol.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Placebo + Ticagrelor	Number of Participants With Ischemic Episode	135 Participants
Aspirin + Ticagrelor	Number of Participants With Ischemic Episode	137 Participants

Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention

Conditions

Keywords

Brief summary

Detailed description

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Recruitment details

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Number of Participants With BARC Type 2, 3, or 5

Number of Participants With Ischemic Episode