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

NCT ID: NCT06855394

Last Updated: 2025-04-11

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 13000 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2011-01-01
• Study Completion Date: 2025-12-31

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; Atherosclerosis of Arteries of the Extremities, Unspecified; Heart Diseases; Stroke; Venous Thromboembolic Disease

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

Cytochrome P450 2C19 Loss-of-function

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

No interventions assigned to this group

Cytochrome P450 2C19 Non-loss-of-function

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

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Florida

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

UF Health

Gainesville, Florida, United States

UF Health

Jacksonville, Florida, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 29891620 (View on PubMed)

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.

Reference Type: RESULT

PMID: 35034351 (View on PubMed)

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.

Reference Type: RESULT

PMID: 32139218 (View on PubMed)

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.

Reference Type: RESULT

PMID: 38899464 (View on PubMed)

Other Identifiers

IRB202302158

Identifier Type: -

Identifier Source: org_study_id