Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-term

Conditions

Atherosclerotic Cardiovascular Disease

Keywords

aspirin, ACSD, PCORI

Brief summary

ADAPTABLE is a pragmatic clinical trial in which 15,000 patients who are at high risk for ischemic events will be randomly assigned in a 1:1 ratio to receive an aspirin dose of 81 mg/day vs. 325 mg/day. Study participants will be enrolled over 38 months. Maximum follow-up will be 50 months. The purpose of the study is to identify the optimal dose of aspirin for secondary prevention in patients with Atherosclerotic cardiovascular disease (ASCVD). The primary endpoint is a composite of all-cause death, hospitalization for MI, or hospitalization for stroke. The primary safety endpoint is hospitalization for major bleeding with an associated blood product transfusion.

Detailed description

In this pragmatic, patient-centered clinical trial, the investigators will compare the effectiveness of two doses of aspirin (81 mg and 325 mg) currently in widespread use in the United States in the secondary-prevention population of patients with established ASCVD. The trial will use a novel format that uses existing electronic health records (EHRs), as well as a web-based patient portal to collect patient-reported outcomes (PROs), and available patient encounter data to supplement/support the EHR. Patients who are identified as candidates for the trial will be directed to the electronic patient portal for the eConsent as well as an abbreviated eligibility confirmation and randomization. One of the important aims of ADAPTABLE is to engage patients, their healthcare providers, and trial investigators in using the infrastructure PCORnet has developed and continues to refine. A total of 15,000 high-risk patients with ASCVD will be randomly assigned (in an open-label fashion) in a 1:1 ratio to instructions to use a daily aspirin dose of either 81 mg or 325 mg daily. The investigators expect the entire sample of patients will be enrolled over 38 months, with a maximum follow-up of 50 months.

Narcisse DI, Whittle J, Rhodes GM, Stebbins AL, Wruck LM, Mulder H, Kripalani S, Muñoz D, Effron MB, Gupta K, Handberg EM, Girotra S, Hess R, Benziger CP, Farrehi P, VanWormer JJ, Knowlton KU, Polonsky TS, Bradley SM, Robertson HR, Hammill BG, Rothman RL, Harrington RA, Jones WS, Hernandez AF.

2025-07-25

10.1016/j.cct.2025.108030

Impact of aspirin dose according to race in secondary prevention of atherosclerotic cardiovascular disease: a secondary analysis of the ADAPTABLE randomised controlled trial

Guillaume Marquis‐Gravel, Hillary Mulder, Lisa Wruck, Catherine P. Benziger, Mark B. Effron et al. (16 authors)

BMJ Open2024-08-012 citations

10.1136/bmjopen-2023-078197

Aspirin Dosing for Secondary Prevention of Atherosclerotic Cardiovascular Disease in Male and Female Patients

Catherine P. Benziger, Amanda Stebbins, Lisa Wruck, Mark B. Effron, Guillaume Marquis‐Gravel et al. (17 authors)

JAMA Cardiology2024-07-106 citations

10.1001/jamacardio.2024.1712

Aspirin Dosing for Secondary Prevention of Atherosclerotic Cardiovascular Disease in Patients Treated With P2Y12 Inhibitors

Saket Girotra, Amanda Stebbins, Lisa Wruck, Guillaume Marquis‐Gravel, Kamal Gupta et al. (20 authors)

Journal of the American Heart Association2023-10-131 citations

10.1161/jaha.123.030385

Effectiveness and Safety of Enteric-Coated vs Uncoated Aspirin in Patients With Cardiovascular Disease

Amber Sleem, Mark B. Effron, Amanda Stebbins, Lisa Wruck, Guillaume Marquis‐Gravel et al. (21 authors)

JAMA Cardiology2023-10-0413 citations

10.1001/jamacardio.2023.3364

Internet Versus Noninternet Participation in a Decentralized Clinical Trial: Lessons From the ADAPTABLE Study

Rebecca Shen, Hillary Mulder, Lisa Wruck, E. Hope Weissler, Holly R. Robertson et al. (19 authors)

Journal of the American Heart Association2023-06-238 citations

10.1161/jaha.122.027899

Outcomes among patients with peripheral artery disease in the Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness (ADAPTABLE) study

E. Hope Weissler, Amanda Stebbins, Lisa Wruck, Daniel Muñoz, Kamal Gupta et al. (15 authors)

Vascular Medicine2023-04-01

10.1177/1358863x231154951

Concordance Between Patient-Reported Health Data and Electronic Health Data in the ADAPTABLE Trial

Emily C. O’Brien, Hillary Mulder, W. Schuyler Jones, Bradley G. Hammill, Amber Sharlow et al. (7 authors)

JAMA Cardiology2022-11-0218 citations

10.1001/jamacardio.2022.3844

Comparative Effectiveness of Aspirin Dosing in Cardiovascular Disease

W. Schuyler Jones, Hillary Mulder, Lisa Wruck, Michael Pencina, Sunil Kripalani et al. (70 authors)

New England Journal of Medicine2021-05-15283 citations

10.1056/nejmoa2102137

Computable Phenotype Implementation for a National, Multicenter Pragmatic Clinical Trial

Faraz S. Ahmad, Iben M. Ricket, Bradley G. Hammill, Lisa Eskenazi, Holly R. Robertson et al. (16 authors)

Circulation Cardiovascular Quality and Outcomes2020-05-2934 citations

10.1161/circoutcomes.119.006292

Rationale and Design of the Aspirin Dosing—A Patient-Centric Trial Assessing Benefits and Long-term Effectiveness (ADAPTABLE) Trial

Guillaume Marquis‐Gravel, Matthew T. Roe, Holly R. Robertson, Robert A. Harrington, Michael Pencina et al. (44 authors)

JAMA Cardiology2020-03-1881 citations

10.1001/jamacardio.2020.0116

Interventions

DRUGaspirin

81mg of aspirin daily vs. 325mg of aspirin daily

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

Inclusion criteria

* Known atherosclerotic cardiovascular disease (ASCVD), defined by a history of prior myocardial infarction, prior coronary angiography showing ≥75% stenosis of at least one epicardial coronary vessel, or prior coronary revascularization procedures (either PCI or CABG), or history of chronic heart disease, CAD, ASCVD * Age ≥ 18 years * No known safety concerns or side effects considered to be related to aspirin, including * No history of significant allergy to aspirin such as anaphylaxis, urticaria, or significant gastrointestinal intolerances * No history of significant GI bleed within the past 12 months * Significant bleeding disorders that preclude the use of aspirin * Access to the Internet. In the event that the CDRNs are notified that a cohort of patients without internet access can be included, then patient agreement will be obtained during the consent process to provide follow-up information by telephone contact with the DCRI Call Center. * Not currently treated with an oral anticoagulant - either warfarin or a novel anticoagulant (dabigatran, rivaroxaban, apixaban, edoxaban) - and not planned to be treated in the future with an oral anticoagulant for existing indications such as atrial fibrillation, deep venous thrombosis, or pulmonary embolism. * Not currently treated with ticagrelor and not planned to be treated in the future with ticagrelor. * Female patients who are not pregnant or nursing an infant * Estimated risk of a major cardiovascular event (MACE) \> 8% over next 3 years as defined by the presence of at least one or more of the following enrichment factors: * Age \> 65 years * Serum creatinine \> 1.5 mg/dL * Diabetes mellitus (Type 1 or Type 2) * 3-vessel coronary artery disease * Cerebrovascular disease and/or peripheral arterial disease * Left ventricular ejection fraction (LVEF) \< 50% * Current cigarette smoker * Chronic systolic or diastolic heart failure * SBP \> 140 (within past 12 mos) * LDL \> 130 (within past 12 mos)

Exclusion criteria

* There will be no exclusions for any upper age limit, comorbid conditions, or concomitant medications other than oral anticoagulants and ticagrelor that are used at the time of randomization, or are planned to be used during the study follow-up. * Patients and sites interested in participating must be part of the listed health systems collaborators.

Design outcomes

Primary

Measure	Time frame
Number of Participants Experiencing All-cause Death, Hospitalization for Nonfatal MI, or Hospitalization for Nonfatal Stroke in High-risk Patients With a History of MI or Documented Atherosclerotic Cardiovascular Disease (ASCVD)	Time of randomization through study completion, approximately 4 years

Secondary

Measure	Time frame	Description
Number of Participants Experiencing All-cause Death	Time of randomization through study completion, approximately 4 years	—
Number of Participants Experiencing Hospitalization for Nonfatal MI	Time of randomization through study completion, approximately 4 years	—
Number of Participants Requiring Coronary Revascularization Procedures (Percutaneous Coronary Intervention [PCI] or Coronary Artery Bypass Grafting [CABG])	Time of randomization through study completion, approximately 4 years	—
Quality of Life and Functional Status, as Measured on a 5-point Scale	2 years	Quality of life measures are based on an ordinal scale from 1-5, where 1 corresponds to the best outcome and 5 to the worst. Model-based mean score estimates are obtained from mixed models of each quality of life measure.
Number of Participants Experiencing Hospitalization for Nonfatal Stroke	Time of randomization through study completion, approximately 4 years	—

Other

Measure	Time frame
Number of Participants Experiencing Hospitalization for Major Bleeding Complications With an Associated Blood Product Transfusion	Time of randomization through study completion, approximately 4 years

Countries

United States

Participant flow

Participants by arm

Arm	Count
ASA 81mg aspirin 81mg aspirin: 81mg of aspirin daily vs. 325mg of aspirin daily	7,540
ASA 325mg aspirin 325mg aspirin: 81mg of aspirin daily vs. 325mg of aspirin daily	7,536
Total	15,076

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Death	357	315
Overall Study	Withdrawal by Subject	221	393

Baseline characteristics

Characteristic	ASA 325mg	Total	ASA 81mg
Age, Continuous	66.8 years	66.8 years	66.9 years
Ethnicity (NIH/OMB) Hispanic or Latino	232 Participants	481 Participants	249 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6737 Participants	13553 Participants	6816 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	567 Participants	1042 Participants	475 Participants
Race (NIH/OMB) American Indian or Alaska Native	45 Participants	114 Participants	69 Participants
Race (NIH/OMB) Asian	64 Participants	146 Participants	82 Participants
Race (NIH/OMB) Black or African American	647 Participants	1311 Participants	664 Participants
Race (NIH/OMB) More than one race	63 Participants	134 Participants	71 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	741 Participants	1381 Participants	640 Participants
Race (NIH/OMB) White	5976 Participants	11990 Participants	6014 Participants
Sex: Female, Male Female	2417 Participants	4724 Participants	2307 Participants
Sex: Female, Male Male	5119 Participants	10352 Participants	5233 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	315 / 7,434	357 / 7,330
other Total, other adverse events	491 / 7,434	471 / 7,330
serious Total, serious adverse events	383 / 7,434	349 / 7,330

Outcome results

Primary

Number of Participants Experiencing All-cause Death, Hospitalization for Nonfatal MI, or Hospitalization for Nonfatal Stroke in High-risk Patients With a History of MI or Documented Atherosclerotic Cardiovascular Disease (ASCVD)

Time frame: Time of randomization through study completion, approximately 4 years

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
ASA 81mg	Number of Participants Experiencing All-cause Death, Hospitalization for Nonfatal MI, or Hospitalization for Nonfatal Stroke in High-risk Patients With a History of MI or Documented Atherosclerotic Cardiovascular Disease (ASCVD)	590 Participants
ASA 325mg	Number of Participants Experiencing All-cause Death, Hospitalization for Nonfatal MI, or Hospitalization for Nonfatal Stroke in High-risk Patients With a History of MI or Documented Atherosclerotic Cardiovascular Disease (ASCVD)	569 Participants

Secondary

Number of Participants Experiencing All-cause Death

Time frame: Time of randomization through study completion, approximately 4 years

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
ASA 81mg	Number of Participants Experiencing All-cause Death	315 Participants
ASA 325mg	Number of Participants Experiencing All-cause Death	357 Participants

Secondary

Number of Participants Experiencing Hospitalization for Nonfatal MI

Time frame: Time of randomization through study completion, approximately 4 years

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
ASA 81mg	Number of Participants Experiencing Hospitalization for Nonfatal MI	228 Participants
ASA 325mg	Number of Participants Experiencing Hospitalization for Nonfatal MI	213 Participants

Secondary

Number of Participants Experiencing Hospitalization for Nonfatal Stroke

Time frame: Time of randomization through study completion, approximately 4 years

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
ASA 81mg	Number of Participants Experiencing Hospitalization for Nonfatal Stroke	102 Participants
ASA 325mg	Number of Participants Experiencing Hospitalization for Nonfatal Stroke	92 Participants

Secondary

Number of Participants Requiring Coronary Revascularization Procedures (Percutaneous Coronary Intervention [PCI] or Coronary Artery Bypass Grafting [CABG])

Time frame: Time of randomization through study completion, approximately 4 years

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
ASA 81mg	Number of Participants Requiring Coronary Revascularization Procedures (Percutaneous Coronary Intervention [PCI] or Coronary Artery Bypass Grafting [CABG])	471 Participants
ASA 325mg	Number of Participants Requiring Coronary Revascularization Procedures (Percutaneous Coronary Intervention [PCI] or Coronary Artery Bypass Grafting [CABG])	446 Participants

Secondary

Quality of Life and Functional Status, as Measured on a 5-point Scale

Quality of life measures are based on an ordinal scale from 1-5, where 1 corresponds to the best outcome and 5 to the worst. Model-based mean score estimates are obtained from mixed models of each quality of life measure.

Time frame: 2 years

Arm	Measure	Group	Value (MEAN)	Dispersion
ASA 81mg	Quality of Life and Functional Status, as Measured on a 5-point Scale	In the past 7 Days, Felt Depressed	1.69 score on a scale	Standard Error 0.01
ASA 81mg	Quality of Life and Functional Status, as Measured on a 5-point Scale	In the past 7 Days, Problems with Sleep	2.06 score on a scale	Standard Error 0.012
ASA 81mg	Quality of Life and Functional Status, as Measured on a 5-point Scale	Able to Run Errands and Shop	1.65 score on a scale	Standard Error 0.011
ASA 81mg	Quality of Life and Functional Status, as Measured on a 5-point Scale	Trouble doing Regular Activities	1.84 score on a scale	Standard Error 0.012
ASA 81mg	Quality of Life and Functional Status, as Measured on a 5-point Scale	In the past 7 Days, Felt Fatigued	2.25 score on a scale	Standard Error 0.012
ASA 81mg	Quality of Life and Functional Status, as Measured on a 5-point Scale	In the past 7 Days, Pain interfered	2.06 score on a scale	Standard Error 0.013
ASA 81mg	Quality of Life and Functional Status, as Measured on a 5-point Scale	Describe Current Health	2.77 score on a scale	Standard Error 0.011
ASA 325mg	Quality of Life and Functional Status, as Measured on a 5-point Scale	In the past 7 Days, Pain interfered	2.02 score on a scale	Standard Error 0.013
ASA 325mg	Quality of Life and Functional Status, as Measured on a 5-point Scale	Describe Current Health	2.8 score on a scale	Standard Error 0.011
ASA 325mg	Quality of Life and Functional Status, as Measured on a 5-point Scale	Able to Run Errands and Shop	1.66 score on a scale	Standard Error 0.012
ASA 325mg	Quality of Life and Functional Status, as Measured on a 5-point Scale	In the past 7 Days, Felt Depressed	1.7 score on a scale	Standard Error 0.011
ASA 325mg	Quality of Life and Functional Status, as Measured on a 5-point Scale	In the past 7 Days, Felt Fatigued	2.27 score on a scale	Standard Error 0.012
ASA 325mg	Quality of Life and Functional Status, as Measured on a 5-point Scale	In the past 7 Days, Problems with Sleep	2.10 score on a scale	Standard Error 0.012
ASA 325mg	Quality of Life and Functional Status, as Measured on a 5-point Scale	Trouble doing Regular Activities	1.88 score on a scale	Standard Error 0.012

Other Pre-specified

Number of Participants Experiencing Hospitalization for Major Bleeding Complications With an Associated Blood Product Transfusion

Time frame: Time of randomization through study completion, approximately 4 years

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
ASA 81mg	Number of Participants Experiencing Hospitalization for Major Bleeding Complications With an Associated Blood Product Transfusion	53 Participants
ASA 325mg	Number of Participants Experiencing Hospitalization for Major Bleeding Complications With an Associated Blood Product Transfusion	44 Participants

Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-term

Conditions

Keywords

Brief summary

Detailed description

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Other

Countries

Participant flow

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Number of Participants Experiencing All-cause Death, Hospitalization for Nonfatal MI, or Hospitalization for Nonfatal Stroke in High-risk Patients With a History of MI or Documented Atherosclerotic Cardiovascular Disease (ASCVD)

Number of Participants Experiencing All-cause Death

Number of Participants Experiencing Hospitalization for Nonfatal MI

Number of Participants Experiencing Hospitalization for Nonfatal Stroke

Number of Participants Requiring Coronary Revascularization Procedures (Percutaneous Coronary Intervention [PCI] or Coronary Artery Bypass Grafting [CABG])

Quality of Life and Functional Status, as Measured on a 5-point Scale

Number of Participants Experiencing Hospitalization for Major Bleeding Complications With an Associated Blood Product Transfusion