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. 2020 Jun 3;20(1):268.
doi: 10.1186/s12872-020-01558-2.

Bedside testing of CYP2C19 gene for treatment of patients with PCI with antiplatelet therapy

Abdullah M Al-Rubaish  1 , Fahad A Al-Muhanna  1 , Abdullah M Alshehri  1 , Mohammed A Al-Mansori  1 , Rudaynah A Alali  1 , Rania M Khalil  1 , Khalid A Al Faraidy  2 , Cyril Cyrus  3 , Mohammed M Sulieman  1 , Chittibabu Vatte  2 , Daniel M F Claassens  4 , Jurriën M Ten Berg  4 , Folkert W Asselbergs  5   6 , Amein K Al-Ali  7
Affiliations

Bedside testing of CYP2C19 gene for treatment of patients with PCI with antiplatelet therapy

Abdullah M Al-Rubaish et al. BMC Cardiovasc Disord. .

Abstract

Background: To mitigate the risk of stent thrombosis, patients treated by percutaneous coronary intervention (PCI) are administered dual anti-platelet therapy comprising aspirin and a platelet P2Y12 receptor inhibitor. Clopidogrel is a prodrug requiring activation by the cytochrome P450 enzyme, CYP2C19. In Saudi Arabia, it has been reported that approximately 26% of the population carries CYP2C19*2 and/or *3 loss-of-function polymorphisms in addition to a high prevalence of CVD.

Methods: This prospective (April 2013-December 2020) parallel assignment clinical trial focuses on ST-Elevation Myocardial Infarction (STEMI) patient outcomes. The clinical trial includes 1500 STEMI patients from two hospitals in the Eastern Province of Saudi Arabia. Patients are assigned to one of two groups; the control arm receives conventional therapy with clopidogrel, while in the active arm the Spartan RX CYP2C19 assay is used to determine the *2 genotype. Carriers of a CYP2C19*2 loss-of-function allele receive prasugrel or ticagrelor, while non-carriers are treated with clopidogrel. Follow-up is one year after primary PCI. The primary end point is the number of patients who develop an adverse major cardiovascular event, including recurrent MI, non-fatal stroke, cardiovascular death, or major bleeding one year after PCI.

Discussion: The risk of stent thrombosis in PCI patients is usually reduced by dual anti-platelet therapy, comprising aspirin and a P2Y12 inhibitor, such as clopidogrel. However, clopidogrel requires activation by the cytochrome P450 enzyme, CYP2C19. Approximately 20% of the population are unable to activate clopidogrel as they possess the CYP2C19*2 loss-of function (LoF) allele. The primary goal of this trial is to study the benefits of treating only those patients that cannot activate clopidogrel with an alternative that has shown to be a more effective platelet inhibitor and does not require bioactivation by the cytochrome P450 enzyme. We expect an improvement in net clinical benefit outcome in the active arm patients, thus supporting pharmacogenetic testing in PCI patients post STEMI.

Trial registration: Trial registration name is "Bedside Testing of CYP2C19 Gene for Treatment of Patients with PCI with Antiplatelet Therapy" (number NCT01823185) retrospectively registered with clinicaltrials.gov on April 4, 2013. This trial is currently at the patient recruitment stage.

Keywords: Clopidogrel; King Fahd hospital; Platelet aggregation inhibitor; Prasugrel; Purinergic P2 receptor antagonists; Ticagrelor.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Trial Schematic
Fig. 2
Fig. 2
Timeline and Milestone
See this image and copyright information in PMC

References

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