Pharmacogenetic and clinical predictors of response to clopidogrel plus aspirin after acute coronary syndrome in Egyptians

Fathy, Shaimaa; Shahin, Mohamed H.; Langaee, Taimour; Khalil, Basma M.; Saleh, Ayman; Sabry, Nirmeen A.; Schaalan, Mona F.; Wakeel, Lamiaa L. El; Cavallari, Larisa H.

doi:10.1097/fpc.0000000000000349

Cited by 10 publications

(4 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Personalized medicine approaches involve the use of patient‐specific factors, including genotype data to predict optimal pharmacotherapy regimens for individual patients. To enable personalized approaches to HF therapy, pharmacogenetic research is needed to uncover genetic factors that, along with clinical factors, underlie differences in response to HF therapy . Herein, we identified genetic and clinical factors that explained a large portion of the variability in response to MRAs.…”

Section: Discussionmentioning

confidence: 99%

“…To enable personalized approaches to HF therapy, pharmacogenetic research is needed to uncover genetic factors that, along with clinical factors, underlie differences in response to HF therapy. 39 Herein, we identified genetic and clinical factors that explained a large portion of the variability in response to MRAs. Specifically, baseline K and the AGT rs699 and CYB11B2 rs1799998 SNPs explained 71% and 63% of variability in ejection fraction and K post-MRA treatment.…”

Section: Genotype and Spironolactone Responsementioning

confidence: 99%

See 1 more Smart Citation

Effect of Genetic and Nongenetic Factors on the Clinical Response to Mineralocorticoid Receptor Antagonist Therapy in Egyptians with Heart Failure

Sarhan

Shahin

Rouby

et al. 2019

Clinical Translational Sci

Self Cite

View full text Add to dashboard Cite

This prospective cohort study evaluated the association between the renin angiotensin aldosterone system genotypes and response to spironolactone in 155 Egyptian patients with heart failure with reduced ejection fraction (HFrEF). Genotype frequencies for AGT rs699 were: CC = 16%, CT = 48%, and TT = 36%. Frequencies for CYP11B2 rs1799998 were: TT = 33%, TC = 50%, and CC = 17%. After 6 months of spironolactone treatment, change in the left ventricular ejection fraction (LVEF) differed by AGT rs699 (CC, 14.6%; TC, 7.9%; TT, 2.7%; P = 2.1E‐26), and CYP11B2 rs1799998 (TT, 9.1%; TC, 8.7%; CC, 1.4%; P = 0.0006) genotypes. Multivariate linear regression showed that the AGT rs699 and CYP11B2 rs1799998 polymorphisms plus baseline serum potassium explained 71% of variability in LVEF improvement (P = 0.001), 63% of variability in serum potassium increase (P = 2.25E‐08), and 39% of the variability in improvement in quality of life (P = 2.3E‐04) with spironolactone therapy. These data suggest that AGT and CYP11B2 genotypes as well as baseline serum K are predictors of spironolactone response in HFrEF.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Genotype and Spironolactone Responsementioning

confidence: 99%

Effect of Genetic and Nongenetic Factors on the Clinical Response to Mineralocorticoid Receptor Antagonist Therapy in Egyptians with Heart Failure

Sarhan

Shahin

Rouby

et al. 2019

Clinical Translational Sci

Self Cite

View full text Add to dashboard Cite

show abstract

“…In 2012, the morbidity of coronary artery disease in the Uygur population of Xinjiang was 24.2%, much higher than the national average (7.2%) [ 13 ]. Polymorphisms of the CYP2C19 gene and clinical factors are strong predictors of cardiovascular outcomes for patients with acute coronary syndrome treated with oral clopidogrel [ 14 , 15 ]. Nevertheless, very little is known about the influence of such factors in Uygur populations.…”

Section: Introductionmentioning

confidence: 99%

Association between cytochrome P450 2C19 polymorphism and clinical outcomes in clopidogrel-treated Uygur population with acute coronary syndrome: a retrospective study

Wang

Bai

et al. 2021

BMC Cardiovasc Disord

View full text Add to dashboard Cite

Background Acute coronary syndrome (ACS) has become a vital disease with high mortality in the Uygur populations. Clopidogrel plays an important role in reducing the risk of recurrent cardiovascular events after ACS; however, it is a prodrug that requires biotransformation by cytochrome P450 (CYP450). Objectives To determine the effect of genetic polymorphisms in CYP2C19*2, *3, and *17, and along with clinical, demographic factors, on variation in response to clinical outcomes in Uygur patients. Methods A total of 351 patients with ACS were treated with clopidogrel and aspirin for at least 12 months; we recorded major adverse cardiovascular events (MACE) or bleeding within 1 year. Multivariable logistic regression analyses were carried out to identify factors associated with MACE or bleeding. Results We analyze risk factors include age, BMI (body mass index), smoking, alcohol intake, NSTEMI (non-ST-segment elevation myocardial infarction), hypertension, dyslipidemia, concomitant medication, CYP2C19*2 carriers, CYP2C19*17 carriers and metabolizer phenotype. CYP2C19*2 carriers had an odds of having MACE of 2.51 (95% CI: 1.534–4.09) compared with noncarriers (P < .001). However, no factors were significantly associated with bleeding (P > 0.05). Conclusion The CYP2C19*2 gene polymorphism contributes to the risk of MACE in dual clopidogrel—treated Uygur population with ACS with or without PCI (percutaneous coronary intervention). These data may provide valuable insights into the genetic polymorphisms affecting clopidogrel metabolism among minority groups in China.

show abstract

“…They found that these patients had an almost equal to three-fold increase in 30-day incidence of major adverse cardiovascular events risk compared with non-AA homozygotes (15). However, these results were not confirmed in an Egyptian acute coronary syndrome patient treated with DAPT, which reported no association with PEAR1 rs12041331 and cardiovascular risks (21). Moreover, the Aspirin in Reducing Events in the Elderly trial analyzed the relationship between PEAR1 rs12041331 and cardiovascular outcomes in a healthy elderly population with no previous atherothrombotic cardiovascular disease (14).…”

Section: Comparison With Prior Studiesmentioning

confidence: 93%

Impact of Platelet Endothelial Aggregation Receptor-1 Genotypes on Long-Term Cerebrovascular Outcomes in Patients With Minor Stroke or Transient Ischemic Attack

Zhang

et al. 2021

Front. Neurol.

View full text Add to dashboard Cite

Background: Platelet endothelial aggregation receptor-1 (PEAR1) rs12041331 has been reported to affect agonist-stimulated platelet aggregation, but it remains unclear whether this variant plays a role in recurrent stroke. Here we assess the clinical relevance of PEAR1 rs12041331 in acute minor ischemic stroke (AMIS) and transient ischemic attack (TIA) Chinese patients treated with dual antiplatelet therapy (DAPT).Methods: We recruited 273 consecutive minor stroke and TIA patients, and Cox proportional hazard regression was used to model the relationship between PEAR1 rs12041331 and thrombotic and bleeding events.Results: Genotyping for PEAR1 rs12041331 showed 49 (18.0%) AA homozygotes, 129 (47.3%) GA heterozygotes, and 95 (34.7%) GG homozygotes. No association was observed between PEAR1 rs12041331 genotype and stroke or composite clinical vascular event rates (ischemic stroke, hemorrhagic stroke, TIA, myocardial infarction, or vascular death) or bleeding events regardless if individuals carried one or two copies of the A allele. Our results suggested that rs12041331 genetic polymorphism was not an important contributor to clinical events in AMIS and TIA patients in the setting of secondary prevention.Conclusions: Our data do provide robust evidence that genetic variation in PEAR1 rs12041331 do not contribute to atherothrombotic or bleeding risk in minor stroke and TIA patients treated with DAPT.

show abstract

Pharmacogenetic and clinical predictors of response to clopidogrel plus aspirin after acute coronary syndrome in Egyptians

Abstract: These results highlight that CYP2C19*2, along with diabetes, and use of proton pump inhibitor and statin are important factors jointly associated with variability in clinical response to DAPT following ACS in Egyptians.

Cited by 10 publications

References 57 publications

Effect of Genetic and Nongenetic Factors on the Clinical Response to Mineralocorticoid Receptor Antagonist Therapy in Egyptians with Heart Failure

Effect of Genetic and Nongenetic Factors on the Clinical Response to Mineralocorticoid Receptor Antagonist Therapy in Egyptians with Heart Failure

Association between cytochrome P450 2C19 polymorphism and clinical outcomes in clopidogrel-treated Uygur population with acute coronary syndrome: a retrospective study

Impact of Platelet Endothelial Aggregation Receptor-1 Genotypes on Long-Term Cerebrovascular Outcomes in Patients With Minor Stroke or Transient Ischemic Attack

Contact Info

Product

Resources

About