What is the clinical evidence from this study?

Study design: RCT. Population: Acute coronary syndrome (ACS) requiring percutaneous coronary intervention (PCI) (n=301). Intervention: CYP2C19 genotype-guided antiplatelet therapy vs. Routine treatment (P2Y12 inhibitor selected by clinical characteristics). Primary outcome: Major adverse cardiovascular or cerebrovascular events (MACCE) (HR 0.281, 95% CI 0.102-0.773, p=0.009).

What does this research mean for the field?

Personalized antiplatelet therapy based on CYP2C19 genotypes significantly reduces major adverse cardiovascular or cerebrovascular events (MACCE) over 12 months without increasing bleeding risk in Chinese patients with acute coronary syndrome undergoing percutaneous coronary intervention. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

June 16, 2021Open Access

Personalized Antiplatelet Therapy Based on CYP2C19 Genotypes in Chinese ACS Patients Undergoing PCI: A Randomized Controlled Trial

Key Result

Personalized antiplatelet therapy based on CYP2C19 genotypes significantly reduced the 12-month risk of major adverse cardiovascular or cerebrovascular events (HR 0.281) compared to routine treatment in Chinese ACS patients undergoing PCI.

Study Design

Type

RCT (n=301)

Blinding

Open-label

Randomization

Blocked randomization

Multicenter

Structured PICO

Does CYP2C19 genotype-guided antiplatelet therapy reduce MACCE in Chinese ACS patients undergoing PCI?

Population

301 Chinese patients with acute coronary syndrome planning to undergo percutaneous coronary intervention, mean age 59.7 ± 9.8 years, 75.1% male.

Intervention

CYP2C19 genotype-guided (*2 and *3 alleles) selection of P2Y12 receptor inhibitors.

Comparator

Routine treatment with P2Y12 receptor inhibitors selected according to clinical characteristics.

Outcome

Composite of major adverse cardiovascular or cerebrovascular events (MACCE) within a 12-month period.composite

CYP2C19 genotype-guided selection of P2Y12 inhibitors significantly reduces MACCE at 12 months compared to routine selection in Chinese ACS patients undergoing PCI, without increasing bleeding.

Main Result

Effect estimate: HR 0.281 (95% CI 0.102-0.773)

Absolute Event Rate: 3.2% vs 10.9%

p-value: p=0.009

Limitations

CYP2C19 allele 17 (gain-of-function) was not detected
Prasugrel was not available as an alternative P2Y12 inhibitor in China
Open-label design might create potential bias
Small number of participants and primary endpoint events
Insufficient statistical power to compare bleeding risk between groups
Single-center trial with mostly Han ethnicity participants limits generalizability
Reasons for patients switching P2Y12 inhibitors were not further studied

Abstract

Background: The clinical benefits of cytochrome P450 (CYP) 2C19 genotype-guided antiplatelet therapy in Asians remain unclear. In this study, we aimed to investigate the clinical outcomes of pharmacogenomic antiplatelet therapy in Chinese patients. Methods: Patients with acute coronary syndrome planning to undergo percutaneous coronary intervention were eligible for this study and were randomly divided into a genotype-guided treatment (GT) group and routine treatment (RT) group, with a ratio of 2:1. Patients in the GT group underwent CYP2C19 genotyping ( * 2 and * 3 alleles), and the results were considered in selecting P2Y 12 receptor inhibitors. Patients in the RT group were treated with P2Y 12 receptor inhibitors according to their clinical characteristics. The primary endpoint was a composite of major adverse cardiovascular or cerebrovascular events (MACCE). The secondary endpoint was significant bleeding events. Results: Finally, 301 patients were enrolled; 75.1% were men and the mean age was 59.7 ± 9.8 years. In total, 281 patients completed the follow-up procedure. The primary endpoint occurred in 16 patients, 6 patients in the GT group and 10 in the RT group. The GT group showed lower MACCE rates than the RT group (6/189 vs. 10/92, 3.2 vs. 10.9%, hazard ratio: 0.281, 95% confidence interval: 0.102–0.773, P = 0.009). There was no statistically difference in significant bleeding events between the GT and RT groups (4.2 vs. 3.3%, hazard ratio: 1.315, 95% confidence interval: 0.349–4.956, P = 0.685). Conclusion: Personalized antiplatelet therapy that is based on CYP2C19 genotypes could decrease MACCE within a 12-month period in Chinese patients with acute coronary syndrome undergoing percutaneous coronary intervention. Clinical Trial Registration: http://www.chictr.org.cn , identifier: ChiCTR2000034352.

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