Prevalence of CYP2C192 and CYP2C193 Allelic Variants and Clopidogrel Use in Patients with Cardiovascular Disease in Trinidad & Tobago.

IF 3 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS Cardiology and Therapy Pub Date : 2024-03-01 Epub Date: 2024-01-29 DOI:10.1007/s40119-024-00348-7

Daniele Jones, Shana Persad-Ramdeensingh, Sheherazade Crystal Abrahim, Naveen Seecheran, Rajini Rani Haraksingh

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Abstract

Introduction: Trinidad & Tobago has the highest prevalence of cardiovascular disease (CVD) in the Caribbean and clopidogrel is a ubiquitously used treatment. Yet, the extent of genetically mediated clopidogrel resistance is unknown. To determine this, we investigated whether the association between CYP2C19*2 and CYP2C19*3 genetic variants and clopidogrel resistance holds, and calculated the frequencies of these in the Trinidadian CVD population.

Methods: Demographic data, clinical data, and a saliva sample were collected under informed consent from 22 patients with CVD on dual anti-platelet therapy whose biochemical resistance to clopidogrel is known, and a further 162 patients accessing the main public CVD clinic in Trinidad and who are either currently being treated or are likely to be treated with clopidogrel. A polymerase chain reaction (PCR) and restriction enzyme digestion procedure was used to genotype each patient for the CYP2C19*2 and CYP2C19*3 allelic variants. Genotype was compared to known clopidogrel resistance in the 22 patients, and to disease status and clopidogrel usage in the larger cohort.

Results: CYP2C19*2 genotype was concordant with clopidogrel resistance. CYP2C19*2 was detected in 61.1% (99/162) of patients and CYP2C19*3 was undetected. Clopidogrel was the most prescribed antiplatelet therapy (42%). A total of 120 people presented with coronary artery disease (CAD) and 52.5% of these (n = 63/120) are currently prescribed clopidogrel. 63.5% (40/63) of patients with CAD who are prescribed clopidogrel carry the CYP2C19*2 allele; ten homozygous and 30 heterozygous. Indian patients comprised 65% of the cohort and were four times more likely to carry the CYP2C19*2 allele than African patients.

Conclusions: A large proportion of Trinidadian patients with CVD who are prescribed or may be prescribed clopidogrel carry genetic variants associated with clopidogrel resistance. These results emphasize the clinical need for further investigation into whether CYP2C19*2 genotype should guide clopidogrel use for the cardiovascular disease population in Trinidad & Tobago. A slide deck is available for this article.

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特立尼达和多巴哥心血管疾病患者中 CYP2C19*2 和 CYP2C19*3 等位基因变异的患病率和氯吡格雷的使用情况。

简介特立尼达和多巴哥是加勒比地区心血管疾病（CVD）发病率最高的国家，氯吡格雷是一种普遍使用的治疗药物。然而，基因介导的氯吡格雷耐药程度尚不清楚。为了确定这一点，我们调查了 CYP2C19*2 和 CYP2C19*3 基因变异与氯吡格雷耐药性之间是否存在关联，并计算了这些变异在特立尼达心血管疾病人群中的频率：在知情同意的情况下，收集了22名正在接受双重抗血小板治疗且已知对氯吡格雷具有生化耐药性的心血管疾病患者的人口统计学数据、临床数据和唾液样本，以及162名在特立尼达岛主要公共心血管疾病诊所就诊且目前正在接受或可能接受氯吡格雷治疗的患者的人口统计学数据、临床数据和唾液样本。采用聚合酶链式反应（PCR）和限制性酶消化程序对每位患者进行 CYP2C19*2 和 CYP2C19*3 等位基因变异的基因分型。将基因型与22名患者已知的氯吡格雷耐药性进行比较，并与更大群体中的疾病状态和氯吡格雷使用情况进行比较：结果：CYP2C19*2基因型与氯吡格雷耐药性一致。61.1%的患者（99/162）检测到CYP2C19*2，未检测到CYP2C19*3。氯吡格雷是处方最多的抗血小板疗法（42%）。共有 120 人患有冠状动脉疾病（CAD），其中 52.5% 的患者（n = 63/120）目前正在接受氯吡格雷治疗。63.5%（40/63）处方氯吡格雷的冠心病患者携带CYP2C19*2等位基因，其中10人为同型，30人为异型。印度患者占队列的 65%，携带 CYP2C19*2 等位基因的可能性是非洲患者的四倍：结论：在处方或可能处方氯吡格雷的特立尼达心血管疾病患者中，有很大一部分携带与氯吡格雷抗性相关的基因变异。这些结果表明，临床上需要进一步研究CYP2C19*2基因型是否应指导特立尼达和多巴哥心血管疾病患者使用氯吡格雷。本文附有幻灯片。

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来源期刊

Cardiology and Therapy CARDIAC & CARDIOVASCULAR SYSTEMS-

CiteScore

5.30

自引率

0.00%

发文量

审稿时长

6 weeks

期刊介绍： Aims and Scope Cardiology and Therapy is an international, open access, peer reviewed (single-blind), rapid-publication journal dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of cardiovascular therapies and interventions, including devices. Studies relating to diagnosis and diagnostics, pharmacoeconomics, public health, quality of life, as well as patient care, management and education are also encouraged. Areas of focus include, but are not limited to, ischaemic heart disease and acute cardiac care, myocardial, valvular, pericardial and congenital heart disease, vascular and pulmonary disease (including hypertension), arrhythmias, heart failure, non-invasive diagnostic techniques, and invasive and interventional cardiology as well as cardiovascular surgery. The journal is of interest to a broad audience of pharmaceutical and healthcare professionals and publishes original research, reviews, case reports/case series, trial protocols and short communications such as commentaries and editorials. Cardiolology and Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of quality research, which may be considered of insufficient interest by other journals. Rapid Publication The journal’s publication timelines aim for a rapid peer review of 2 weeks. If an article is accepted it will be published 3–4 weeks from acceptance. The rapid timelines are achieved through the combination of a dedicated in-house editorial team, who manage article workflow, and an extensive Editorial and Advisory Board who assist with peer review. This allows the journal to support the rapid dissemination of research, whilst still providing robust peer review. Combined with the journal’s open access model this allows for the rapid, efficient communication of the latest research and reviews, fostering the advancement of cardiovascular therapies. Personal Service The journal’s dedicated in-house editorial team offer a personal “concierge service” meaning authors will always have an editorial contact able to update them on the status of their manuscript. The editorial team check all manuscripts to ensure that articles conform to the most recent COPE, GPP and ICMJE publishing guidelines. This supports the publication of ethically sound and transparent research. Digital Features and Plain Language Summaries Cardiology and Therapy offers a range of additional features designed to increase the visibility, readership and educational value of the journal’s content. Each article is accompanied by key summary points, giving a time-efficient overview of the content to a wide readership. Articles may be accompanied by plain language summaries to assist readers who have some knowledge of, but not in-depth expertise in, the area to understand the scientific content and overall implications of the article. The journal also provides the option to include various types of digital features including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations. All additional features are peer reviewed to the same high standard as the article itself. If you consider that your paper would benefit from the inclusion of a digital feature, please let us know. 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Peer Review Process Upon submission, manuscripts are assessed by the editorial team to ensure they fit within the aims and scope of the journal and are also checked for plagiarism. All suitable submissions are then subject to a comprehensive single-blind peer review. Reviewers are selected based on their relevant expertise and publication history in the subject area. The journal has an extensive pool of editorial and advisory board members who have been selected to assist with peer review based on the afore-mentioned criteria. At least two extensive reviews are required to make the editorial decision, with the exception of some article types such as Commentaries, Editorials and Letters which are generally reviewed by one member of the Editorial Board. Where reviewer recommendations are conflicted, the editorial board will be contacted for further advice and a presiding decision. Manuscripts are then either accepted, rejected or authors are required to make major or minor revisions (both reviewer comments and editorial comments may need to be addressed). Once a revised manuscript is re-submitted, it is assessed along with the responses to reviewer comments and if it has been adequately revised it will be accepted for publication. Accepted manuscripts are then copyedited and typeset by the production team before online publication. Appeals against decisions following peer review are considered on a case by case basis and should be sent to the journal editor. Preprints We encourage posting of preprints of primary research manuscripts on preprint servers, authors’ or institutional websites, and open communications between researchers whether on community preprint servers or preprint commenting platforms. Posting of preprints is not considered prior publication and will not jeopardize consideration in our journals. 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