Genetic Testing of CYP2C19 in Prognostic Evaluation of Long-Term Major Adverse Cardiac and Vascular Events

NCT06855394 | Active Not Recruiting

• 1 other identifier: IRB202302158
• Study Type: observational
• Target: 13,000
• Locations: 1 country
• Sites: 2

Brief Summary

Several studies have shown that the efficacy of clopidogrel for secondary prevention of major adverse cardiovascular events (MACE), including acute coronary syndrome, depends on the polymorphism of the CYP2C19 gene. However, studies with large sample sizes and long-term follow-up are missing. Moreover, the impact of this polymorphism on the risk of major adverse limb events (MALE), particularly in patients with peripheral artery disease of the lower limb, is unexplored. Additionally, the impact of CYP2C19 gene polymorphism on clopidogrel effectiveness in preventing recurrent stroke in diverse populations is unknown since most of the data are from Asian ancestry populations. We hypothesize that patients with CYP2C19 gene loss of function alleles are at high risk of MACE and MALE compared to those without loss of function alleles at long-term follow-up. We propose to assess MACE and MALE in a large cohort of patients with available CYP2C19 genotypes treated at the University of Florida Health to evaluate the impact of CYP2C19 gene polymorphisms on the risk of new or recurrent events at long-term follow-up. Our specific aims are Aim 1) to determine the impact of CYP2C19 gene polymorphisms (loss of function alleles vs. non-loss of function alleles) on the risk of MACE (a composite of all-cause death, non-fatal MI, and non-fatal stroke) at long-term follow-up; Aim 2) to evaluate the impact of CYP2C19 gene polymorphisms (loss of function alleles vs. non-loss of function alleles) on the risk of MALE (a composite of limb amputations, chronic threatening limb ischemia, acute limb ischemia, and limb revascularization) at long-term follow-up; and Aim 3) to evaluate the impact of CYP2C19 gene polymorphisms (loss of function alleles vs. non-loss of function alleles) on the risk of cerebrovascular events (CVE, a composite of any stroke and transient ischemic attack) at long-term follow-up.

Conditions

Atherosclerotic Vascular Disease; Coronary Arterial Disease (CAD); Atherosclerosis of Coronary Artery; Heart Diseases; Stroke; Venous Thromboembolic Disease; Atherosclerosis of Arteries of the Extremities, Unspecified

Keywords

Cardiovascular disease; Atherosclerotic vascular disease; Coronary artery disease; Stroke

Outcome Measures

Primary Outcomes (1)

• Major adverse cardiovascular events

  Defined as the composite of all-cause death, non-fatal MI, ornon-fatal stroke

  5 years

Secondary Outcomes (7)

• Major adverse limb events

  5 years

• Net adverse clinical events

  5 years

• Cerebrovascular event

  5 years

• Major bleeding

  5 years

• Minor bleeding

  5 years

Study Arms (2)

Cytochrome P450 2C19 Loss-of-function

Patients carriers of a Cytochrome P450 2C19 loss-of-function allele (i.e., \*2 or \*3)

Cytochrome P450 2C19 Non-loss-of-function

Patients without a Cytochrome P450 2C19 loss-of-function allele.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with systemic atherosclerosis.

You may qualify if:

• All patients aged ≥18 years with available CYP2C19 genotyping results obtained within the predefined period.

You may not qualify if:

• Absence of CYP2C19 genotyping results obtained within the predefined period.

Sponsors & Collaborators

• University of Florida: lead

Study Sites (2)

UF Health

Gainesville, Florida, 32608, United States

Location

UF Health

Jacksonville, Florida, 32209, United States

Location

Related Publications (4)

• Garcia-Garcia HM, McFadden EP, Farb A, Mehran R, Stone GW, Spertus J, Onuma Y, Morel MA, van Es GA, Zuckerman B, Fearon WF, Taggart D, Kappetein AP, Krucoff MW, Vranckx P, Windecker S, Cutlip D, Serruys PW; Academic Research Consortium. Standardized End Point Definitions for Coronary Intervention Trials: The Academic Research Consortium-2 Consensus Document. Circulation. 2018 Jun 12;137(24):2635-2650. doi: 10.1161/CIRCULATIONAHA.117.029289.

  PMID: 29891620 RESULT

• Lee CR, Luzum JA, Sangkuhl K, Gammal RS, Sabatine MS, Stein CM, Kisor DF, Limdi NA, Lee YM, Scott SA, Hulot JS, Roden DM, Gaedigk A, Caudle KE, Klein TE, Johnson JA, Shuldiner AR. Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2C19 Genotype and Clopidogrel Therapy: 2022 Update. Clin Pharmacol Ther. 2022 Nov;112(5):959-967. doi: 10.1002/cpt.2526. Epub 2022 Feb 8.

  PMID: 35034351 RESULT

• Angiolillo DJ, Capodanno D, Danchin N, Simon T, Bergmeijer TO, Ten Berg JM, Sibbing D, Price MJ. Derivation, Validation, and Prognostic Utility of a Prediction Rule for Nonresponse to Clopidogrel: The ABCD-GENE Score. JACC Cardiovasc Interv. 2020 Mar 9;13(5):606-617. doi: 10.1016/j.jcin.2020.01.226.

  PMID: 32139218 RESULT

• Pereira NL, Cresci S, Angiolillo DJ, Batchelor W, Capers Q 4th, Cavallari LH, Leifer D, Luzum JA, Roden DM, Stellos K, Turrise SL, Tuteja S; American Heart Association Professional/Public Education and Publications Committee of the Council on Genomic and Precision Medicine; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology; Council on Peripheral Vascular Disease; and Stroke Council. CYP2C19 Genetic Testing for Oral P2Y12 Inhibitor Therapy: A Scientific Statement From the American Heart Association. Circulation. 2024 Aug 6;150(6):e129-e150. doi: 10.1161/CIR.0000000000001257. Epub 2024 Jun 20.

  PMID: 38899464 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Buccal swab used to extract DNA for evaluation of specific hepatic cytochrome P450 2C19 alleles

MeSH Terms

Conditions

Atherosclerosis; Coronary Artery Disease; Heart Diseases; Stroke; Cardiovascular Diseases

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Coronary Disease; Myocardial Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 28, 2025
• First Posted: March 3, 2025
• Study Start: January 1, 2011
• Primary Completion: December 31, 2023
• Study Completion (Estimated): December 31, 2026
• Last Updated: March 31, 2026

Record last verified: 2026-03

Locations

US (2)