Impact of genetic variants on clinical outcome after percutaneous coronary intervention in elderly patients

Cha, Jeong-Dan; Park, Jae Hyoung; Joo, Hyung Joon; Hong, Soon Jun; Ahn, Tae Hoon; Kim, Byeong Keuk; Shin, Won-Yong; Ahn, Sung Gyun; Yoon, Jung Han; Kim, Yong Hoon; Cho, Yun Hyeong; Kang, Woong Chol; Kim, Weon; Lim, Young‐Hyo; Gwon, Hyeon Cheol; Choi, Woong; Lim, Do Sun

doi:10.18632/aging.202799

Cited by 3 publications

(4 citation statements)

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“…We have previously reported a genetic study of 811 older patients (aged ≥75 years). 27 The primary end point was a composite of MI and death at 1 year. Regarding the CYP2C19 allele, the PM group had a significantly higher risk for the primary end point (HR, 2.43 [95% CI, 1.12–5.24]; P =0.024) than the IM/NM group.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Impact of CYP2C19 Genotypes on Long‐Term Clinical Outcomes in Older Patients After Percutaneous Coronary Intervention

Kim,

Lee,

Cha

et al. 2024

JAHA

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Background Carriers of CYP2C19 loss‐of‐function alleles have increased adverse events after percutaneous coronary intervention, but limited data are available for older patients. We aimed to evaluate the prognostic impact of CYP2C19 genotypes on clinical outcomes in older patients after percutaneous coronary intervention. Methods and Results The study included 1201 older patients (aged ≥75 years) who underwent percutaneous coronary intervention and received clopidogrel‐based dual antiplatelet therapy in South Korea. Patients were grouped on the basis of CYP2C19 genotypes. The primary outcome was 3‐year major adverse cardiac events, defined as a composite of cardiac death, myocardial infarction, and stent thrombosis. Older patients were grouped into 3 groups: normal metabolizer (36.6%), intermediate metabolizer (48.1%), and poor metabolizer (15.2%). The occurrence of the primary outcome was significantly different among the groups (3.1, 7.0, and 6.2% in the normal metabolizer, intermediate metabolizer, and poor metabolizer groups, respectively; P =0.02). The incidence rate of all‐cause death at 3 years was greater in the intermediate metabolizer and poor metabolizer groups (8.1% and 9.2%, respectively) compared with that in the normal metabolizer group (3.5%, P =0.03) without significant differences in major bleeding. In the multivariable analysis, the intermediate metabolizer and poor metabolizer groups were independent predictors of 3‐year clinical outcomes. Conclusions In older patients, the presence of any CYP2C19 loss‐of‐function allele was found to be predictive of a higher incidence of major adverse cardiac events within 3 years following percutaneous coronary intervention. This finding suggests a need for further investigation into an optimal antiplatelet strategy for older patients. Registration URL: https://clinicaltrials.gov . Identifier: NCT04734028.

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Section: Discussionmentioning

confidence: 99%

Prognostic Impact of CYP2C19 Genotypes on Long‐Term Clinical Outcomes in Older Patients After Percutaneous Coronary Intervention

Kim,

Lee,

Cha

et al. 2024

JAHA

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“…Another SNP associated with H1/H2 haplotype, G52T, can negatively impact PCI outcomes in elderly patients. In a recent study that included 811 patients aged ≥ 75 years of age, TT homozygotes had a higher risk of bleeding during a 1-year follow-up compared with GG and GT genotypes (adjusted HR: 3.87, 95% CI: 1.41–10.68, p = 0.009) [ 72 ]. Although T744C was not one of the investigated variants, the T allele in G52T is associated with the H2 haplotype.…”

Section: H1/h2 Haplotype and Related Allelesmentioning

confidence: 99%

Influence of Genetic and Epigenetic Factors of P2Y12 Receptor on the Safety and Efficacy of Antiplatelet Drugs

Danielak

Pawlak

Główka

et al. 2022

Cardiovasc Drugs Ther

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Purpose P2Y12 receptor inhibitors are drugs that decrease the risk of stent thrombosis and lower the long-term risk of non-stent-related myocardial infarction and stroke. They inhibit the binding of adenosine diphosphate (ADP) to the P2Y12 receptor and effectively reduce platelet reactivity. However, considerable variability in the pharmacodynamics response contributes to a failure of antiplatelet therapy; this phenomenon is especially notorious for older drugs, such as clopidogrel. Some genetic polymorphisms associated with these drugs’ metabolic pathway, especially in the CYP2C19 gene, can significantly decrease antiplatelet efficacy. There are few reports on the variability stemming from the target of this drug class that is the P2Y12 receptor itself. Results and conclusion This review summarizes the results of research that focus on the influence of P2Y12 genetic polymorphisms on the pharmacodynamics and the efficacy of P2Y12 inhibitors. We found that the conclusions of the studies are unequivocal, and despite several strong candidates, such as G52T (rs6809699) or T744C (rs2046934), they may not be independent predictors of the inadequate response to the drug. Most probably, P2Y12 genetic polymorphisms contribute to the effect exerted by other gene variants (such as CYP2C19*2/*3/*17), drug interactions, or patient habits, such as smoking. Also, epigenetic modifications, such as methylation or miRNA levels, may play a role in the efficacy of antiplatelet treatment.

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“… 7 , 8 Numerous studies have reported that aging is strongly associated with an increased incidence of ischemic and bleeding events. 9 , 10 Moreover, because PRU continuously increases with age, HPR in older patients may translate into an increased risk of ischemic events. 4 , 9 , 10 Meanwhile, although BMI is associated with adverse clinical outcomes in patients after PCI and low response to clopidogrel, in other words, increased PRU, 8 , 11 , 12 few studies have reported an association between BMI and PRU in terms of adverse ischemic outcomes.…”

mentioning

confidence: 99%

“… 9 , 10 Moreover, because PRU continuously increases with age, HPR in older patients may translate into an increased risk of ischemic events. 4 , 9 , 10 Meanwhile, although BMI is associated with adverse clinical outcomes in patients after PCI and low response to clopidogrel, in other words, increased PRU, 8 , 11 , 12 few studies have reported an association between BMI and PRU in terms of adverse ischemic outcomes. Moreover, there are little data on the association between age or BMI and PRU on major bleeding.…”

mentioning

confidence: 99%

Association of Age‐ and Body Mass Index‐Stratified High On‐Treatment Platelet Reactivity With Coronary Intervention Outcomes in East Asian Patients

Cha,

Lee,

Park

et al. 2024

JAHA

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Background Although age and body mass index (BMI) significantly affect platelet reactivity units and clinical outcomes after percutaneous coronary intervention, there are limited data on the relationship between high on‐treatment platelet reactivity (HPR) and clinical outcomes on age and BMI differences. Thus, we investigated the association of HPR with clinical outcomes according to age and BMI. Methods and Results The study analyzed 11 714 patients who underwent platelet function tests after percutaneous coronary intervention. The primary end point was the occurrence of major adverse cardiac and cerebrovascular events (MACCEs), whereas the secondary end point was major bleeding. HPR was defined as platelet reactivity units ≥252. Patients were categorized by age (<67 years of age or ≥67 years of age) and BMI (≤22.6 kg/m 2 or >22.6 kg/m 2 ). Patients <67 years of age with HPR had increases in both MACCEs (adjusted hazard ratio [HR], 1.436 [95% CI, 1.106–1.867]; P =0.007) and major bleeding (adjusted HR, 1.584 [95% CI, 1.095–2.290]; P =0.015) compared with the those with non‐HPR, respectively. In patients ≥67 years of age with HPR, there were no differences in MACCEs, but there was a decrease in major bleeding (adjusted HR, 0.721 [95% CI, 0.542–0.959]; P =0.024). Meanwhile, patients with HPR with BMI >22.6 kg/m 2 had increases in MACCEs (adjusted HR, 1.387 [95% CI, 1.140–1.688]; P =0.001). No differences were shown in major bleeding. Conclusions HPR was linked to an increase in MACCEs or a decrease in major bleeding in patients after percutaneous coronary intervention, depending on age and BMI. This study is the first to observe that clinical outcomes in patients with HPR after percutaneous coronary intervention may vary based on age and BMI. Because the study is observational, the results should be viewed as hypothesis generating and emphasize the need for randomized clinical trials.

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Impact of genetic variants on clinical outcome after percutaneous coronary intervention in elderly patients

Cited by 3 publications

References 34 publications

Prognostic Impact of CYP2C19 Genotypes on Long‐Term Clinical Outcomes in Older Patients After Percutaneous Coronary Intervention

Prognostic Impact of CYP2C19 Genotypes on Long‐Term Clinical Outcomes in Older Patients After Percutaneous Coronary Intervention

Influence of Genetic and Epigenetic Factors of P2Y12 Receptor on the Safety and Efficacy of Antiplatelet Drugs

Association of Age‐ and Body Mass Index‐Stratified High On‐Treatment Platelet Reactivity With Coronary Intervention Outcomes in East Asian Patients

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