Utility of a pharmacogenetic-driven algorithm in guiding dual antiplatelet therapy for patients undergoing coronary drug-eluting stent implantation in China.

Abstract

PURPOSES:

The POPular Risk Score (PRiS), a pharmacogenetic-driven algorithm consisting of CYP2C19 genotype, platelet reactivity, and clinical risk factors, is developed to evaluate ischemic risk and guide dual antiplatelet therapy (DAPT). This study aimed to evaluate the efficacy and safety of DAPT in accordance with the PRiS in patients undergoing drug-eluting stent (DES) implantation.

METHODS:

A total of 1757 patients recruited in this cohort study were divided into four groups according to the PRiS and type of P2Y12 receptor inhibitor treatment at discharge. The primary endpoint was major adverse cardiovascular events (MACE, a composite of cardiovascular death, myocardial infarction, stroke, definite or probable stent thrombosis, and target vessel revascularization) during 1-year follow-up. The safety endpoints were defined by Bleeding Academic Research Consortium (BARC) criteria as major bleeding (BARC 3a, 3b, 3c, and 5) and clinically relevant bleeding (BARC 2, 3a, 3b, 3c, and 5).

RESULTS:

Among 1046 patients with PRiS < 2 and 711 patients with PRiS ≥ 2, 34.2% and 38.3% of them were treated with ticagrelor, respectively. The PRiS ≥ 2 was an independent predictor for the 1-year incidence of MACE (HR(95%CI): 2.09 (1.37-3.20), p = 0.001). Multivariable Cox regression indicated that in the PRiS ≥ 2 group, ticagrelor was superior to clopidogrel in reducing the risk of MACE (HR(95%CI): 0.53 (0.29-0.98), p = 0.042), without increasing the bleeding risk. On the other hand, in the PRiS < 2 group, clopidogrel treatment was related to a remarkably lower rate of BARC class ≥ 2 bleeding (HR(95%CI): 0.39 (0.20-0.72), p = 0.003), but comparable incidences of MACE and BARC class ≥ 3 bleeding during 1-year follow-up. Similar associations between P2Y12 receptor inhibitors and 1-year endpoints in the PRiS < 2 and PRiS ≥ 2 group could also be identified in propensity score-weighted analysis and propensity score-matched analysis.

CONCLUSION:

Tailored DAPT based on the PRiS could assist in improving the prognosis of patients undergoing DES implantation. Further randomized controlled trials are required to provide more evidence for PRiS-guided DAPT.

• Authors: Si-Qi Lyu, Jun Zhu, Juan Wang, Shuang Wu, Han Zhang, Xing-Hui Shao, Yan-Min Yang
• Journal: European journal of clinical pharmacology (Eur J Clin Pharmacol) Vol. 78 Issue 2 Pg. 215-225 (Feb 2022) ISSN: 1432-1041 [Electronic] Germany
• PMID: 34636928 (Publication Type: Journal Article)
• Copyright: © 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Chemical References

• Platelet Aggregation Inhibitors
• Purinergic P2Y Receptor Antagonists
• Clopidogrel
• CYP2C19 protein, human
• Cytochrome P-450 CYP2C19
• Ticagrelor
• Ticlopidine
• Aspirin

Topics

• Aged
• Algorithms
• Asian People (genetics)
• Aspirin (therapeutic use)
• Cardiovascular Diseases
• China
• Clopidogrel (therapeutic use)
• Comorbidity
• Cytochrome P-450 CYP2C19 (genetics)
• Drug-Eluting Stents
• Dual Anti-Platelet Therapy (adverse effects, methods)
• Female
• Health Behavior
• Hemorrhage (chemically induced)
• Humans
• Male
• Middle Aged
• Pharmacogenetics
• Platelet Aggregation Inhibitors (adverse effects)
• Purinergic P2Y Receptor Antagonists (adverse effects)
• Risk Assessment
• Risk Factors
• Sociodemographic Factors
• Ticagrelor
• Ticlopidine (therapeutic use)