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. 2015 Aug 15;8(8):13310-6.
eCollection 2015.

A randomized controlled trial to assess the efficacy and safety of doubling dose clopidogrel versus ticagrelor for the treatment of acute coronary syndrome in patients with CYP2C19*2 homozygotes

Ran Xiong  1 , Wenxian Liu  1 , Liying Chen  1 , Tieduo Kang  1 , Shangqiu Ning  1 , Jiang Li  1
Affiliations

A randomized controlled trial to assess the efficacy and safety of doubling dose clopidogrel versus ticagrelor for the treatment of acute coronary syndrome in patients with CYP2C19*2 homozygotes

Ran Xiong et al. Int J Clin Exp Med. .

Abstract

Background: Compared with non-reversible, indirect P2Y12 inhibitor clopidogrel, ticagrelor is a reversible, direct acting inhibitor. The CYP2C19*2 allele is a common genetic variant in individuals that need given higher clopidogrel in acute coronary syndrome patients.

Objective: We aimed to assess a pharmacogenetic approach of doubling dose clopidogrel compare with standard dose of ticagrelor among carriers with the CYP2C19*2 homozygotes.

Materials and methods: We compared ticagrelor (180 mg loading dose, 90 mg twice daily thereafter) with clopidogrel (600 mg loading dose, 150 mg daily thereafter) for the prevention of cardiovascular events in CYP2C19*2 homozygotes patients admitted to the hospital with an acute coronary syndrome, with or without ST-segment elevation.

Results: After genetic test to identify carriers of the CYP2C19*2 allele from 2295 patients, 224 cases with CYP2C19*2 homozygotes were enrolled into our prospective, randomized trial. Patients were random assignment with colpidogrel group (n = 112) and ticagrelor group (n = 112). The two groups were similar in terms of baseline characteristics. After the first 600 mg loading dose of clopidogrel, patients carrying two CYP2C19*2 allele had weaker PRU inhibition (39.8±37.4 vs 27.9±12.4; P = 0.001) and more bleeding adverse events (20.5% vs. 7.1%; hazard ratio = 2.88; 95% [CI], 1.34-6.15; P = 0.001) compared to those taking standard dose of ticagrelor.

Conclusions: In CYP2C19*2 carriers with ACS, ticagrlor is as effective as high clopidogrel in reducing platelet reactivity, particularly in first days. This study suggests that ticagrelor may be much better than doubling dose clopidogrel in patients with CYP2C19*2 in according to platelet reactivity monitoring. Use of ticagrelor instead of clopidogrel may eliminate the need for genetic testing and lead to less mild bleeding adverse.

Keywords: Acute coronary syndrome; clopidgrel; platelet aggregation inhibitors; randomized controlled trial; ticagrelor.

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Figures

Figure 1
Figure 1
Study Flow Chart.
Figure 2
Figure 2
Platelet reactivity units (PRU) after treatment sequence.
Figure 3
Figure 3
Individual platelet reactivity unit values at day 30 after treatment.
See this image and copyright information in PMC

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