Abstract
Introduction: High on-treatment platelet reactivity (HTPR) to clopidogrel imparts an increased risk for ischemic events in adults with coronary artery disease. Platelet reactivity varies with ethnicity and is influenced by both clinical and genetic variables; however, no clopidogrel pharmacogenetic studies with Puerto Rican patients have been reported. Therefore, we sought to identify clinical and genetic determinants of on-treatment platelet reactivity in a cohort of Puerto Rican patients with cardiovascular disease. Methods: We performed a retrospective study of 111 patients on 75 mg/day maintenance dose of clopidogrel. Patients were allocated into 2 groups: Group I, without HTPR; and Group II, with HTPR. Platelet function was measured ex vivo using the VerifyNow® P2Y12 assay and HTPR was defined as P2Y12 reaction units (PRU) ≥230. Genotyping testing was performed using Taqman Genotyping Assays. ® Results: The mean PRU across the cohort was 203±61 PRU (range 8–324), and 42 (38%) patients had HTPR. Multiple logistic regression showed that 27% of the total variation in PRU was explained by a history of diabetes mellitus, hematocrit, CYP2C19*2, and PON1 p.Q192R. Body mass index (odds ratio [OR]=1.15; 95% CI: 1.03–1.27), diabetes mellitus (OR=3.46; 95% CI: 1.05–11.43), hematocrit (OR=0.75; 95% CI: 0.65–0.87), and CYP2C19*2 (OR=4.44; 95% CI: 1.21–16.20) were the only independent predictors of HTPR. Conclusion: Moreover, we propose a predictive model to determine PRU values as measured by VerifyNow P2Y12 assay for the Puerto Rican Hispanic population. This model has the potential to identify Hispanic patients at higher risk for adverse events on clopidogrel.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 95-106 |
| Number of pages | 12 |
| Journal | Pharmacogenomics and Personalized Medicine |
| Volume | 11 |
| DOIs | |
| State | Published - Jun 8 2018 |
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Keywords
- Clopidogrel
- Genotyping
- Hispanics
- Platelet reactivity
- Puerto Rico
ASJC Scopus subject areas
- Molecular Medicine
- Pharmacology
Cite this
Pharmacogenetic association study on clopidogrel response in Puerto Rican hispanics with cardiovascular disease : A novel characterization of a Caribbean population. / Hernandez-Suarez, Dagmar F.; Botton, Mariana R.; Scott, Stuart A.; Tomey, Matthew I.; Garcia, Mario J.; Wiley, Jose M.; Villablanca, Pedro A.; Melin, Kyle; Lopez-Candales, Angel; Renta, Jessicca Y.; Duconge, Jorge.
In: Pharmacogenomics and Personalized Medicine, Vol. 11, 08.06.2018, p. 95-106.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Pharmacogenetic association study on clopidogrel response in Puerto Rican hispanics with cardiovascular disease
T2 - A novel characterization of a Caribbean population
AU - Hernandez-Suarez, Dagmar F.
AU - Botton, Mariana R.
AU - Scott, Stuart A.
AU - Tomey, Matthew I.
AU - Garcia, Mario J.
AU - Wiley, Jose M.
AU - Villablanca, Pedro A.
AU - Melin, Kyle
AU - Lopez-Candales, Angel
AU - Renta, Jessicca Y.
AU - Duconge, Jorge
PY - 2018/6/8
Y1 - 2018/6/8
N2 - Introduction: High on-treatment platelet reactivity (HTPR) to clopidogrel imparts an increased risk for ischemic events in adults with coronary artery disease. Platelet reactivity varies with ethnicity and is influenced by both clinical and genetic variables; however, no clopidogrel pharmacogenetic studies with Puerto Rican patients have been reported. Therefore, we sought to identify clinical and genetic determinants of on-treatment platelet reactivity in a cohort of Puerto Rican patients with cardiovascular disease. Methods: We performed a retrospective study of 111 patients on 75 mg/day maintenance dose of clopidogrel. Patients were allocated into 2 groups: Group I, without HTPR; and Group II, with HTPR. Platelet function was measured ex vivo using the VerifyNow® P2Y12 assay and HTPR was defined as P2Y12 reaction units (PRU) ≥230. Genotyping testing was performed using Taqman Genotyping Assays. ® Results: The mean PRU across the cohort was 203±61 PRU (range 8–324), and 42 (38%) patients had HTPR. Multiple logistic regression showed that 27% of the total variation in PRU was explained by a history of diabetes mellitus, hematocrit, CYP2C19*2, and PON1 p.Q192R. Body mass index (odds ratio [OR]=1.15; 95% CI: 1.03–1.27), diabetes mellitus (OR=3.46; 95% CI: 1.05–11.43), hematocrit (OR=0.75; 95% CI: 0.65–0.87), and CYP2C19*2 (OR=4.44; 95% CI: 1.21–16.20) were the only independent predictors of HTPR. Conclusion: Moreover, we propose a predictive model to determine PRU values as measured by VerifyNow P2Y12 assay for the Puerto Rican Hispanic population. This model has the potential to identify Hispanic patients at higher risk for adverse events on clopidogrel.
AB - Introduction: High on-treatment platelet reactivity (HTPR) to clopidogrel imparts an increased risk for ischemic events in adults with coronary artery disease. Platelet reactivity varies with ethnicity and is influenced by both clinical and genetic variables; however, no clopidogrel pharmacogenetic studies with Puerto Rican patients have been reported. Therefore, we sought to identify clinical and genetic determinants of on-treatment platelet reactivity in a cohort of Puerto Rican patients with cardiovascular disease. Methods: We performed a retrospective study of 111 patients on 75 mg/day maintenance dose of clopidogrel. Patients were allocated into 2 groups: Group I, without HTPR; and Group II, with HTPR. Platelet function was measured ex vivo using the VerifyNow® P2Y12 assay and HTPR was defined as P2Y12 reaction units (PRU) ≥230. Genotyping testing was performed using Taqman Genotyping Assays. ® Results: The mean PRU across the cohort was 203±61 PRU (range 8–324), and 42 (38%) patients had HTPR. Multiple logistic regression showed that 27% of the total variation in PRU was explained by a history of diabetes mellitus, hematocrit, CYP2C19*2, and PON1 p.Q192R. Body mass index (odds ratio [OR]=1.15; 95% CI: 1.03–1.27), diabetes mellitus (OR=3.46; 95% CI: 1.05–11.43), hematocrit (OR=0.75; 95% CI: 0.65–0.87), and CYP2C19*2 (OR=4.44; 95% CI: 1.21–16.20) were the only independent predictors of HTPR. Conclusion: Moreover, we propose a predictive model to determine PRU values as measured by VerifyNow P2Y12 assay for the Puerto Rican Hispanic population. This model has the potential to identify Hispanic patients at higher risk for adverse events on clopidogrel.
KW - Clopidogrel
KW - Genotyping
KW - Hispanics
KW - Platelet reactivity
KW - Puerto Rico
UR - http://www.scopus.com/inward/record.url?scp=85057111383&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85057111383&partnerID=8YFLogxK
U2 - 10.2147/PGPM.S165805
DO - 10.2147/PGPM.S165805
M3 - Article
AN - SCOPUS:85057111383
VL - 11
SP - 95
EP - 106
JO - Pharmacogenomics and Personalized Medicine
JF - Pharmacogenomics and Personalized Medicine
SN - 1178-7066
ER -