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Cytochrome p450 gene variants, race, and mortality among clopidogrel-treated patients after acute myocardial infarction.

ABSTRACT: Clopidogrel is recommended after acute myocardial infarction but has variable efficacy and safety, in part related to the effect of cytochrome P450 (CYP) polymorphisms on its metabolism. The effect of CYP polymorphisms on cardiovascular events among clopidogrel-treated patients after acute myocardial infarction remains controversial, and no studies to date have investigated the association of CYP variants with outcomes in black patients.Subjects (2732: 2062 whites; 670 blacks) hospitalized with acute myocardial infarction enrolled in the prospective, multicenter TRIUMPH study were genotyped for CYP polymorphisms. The majority of whites (79%) and blacks (64.4%) were discharged on clopidogrel. Among whites, carriers of the loss-of-function CYP2C19*2 allele had significantly increased 1-year mortality (adjusted hazards ratio [HR]: 1.70; confidence interval [CI]: 1.01-2.86; P=0.046) and a trend toward increased rate of recurrent MI (adjusted HR: 2.10; CI: 0.95-4.63; P=0.066). Among blacks, increased 1-year mortality was associated with the gain-of-function CYP2C19*17 allele (adjusted HR for *1/*17 versus *1/*1: 2.02; CI: 0.92-4.44; *17/*17 versus *1/*1: 8.97; CI: 3.34-24.10; P<0.0001) and the CYP1A2*1C allele (adjusted HR for *1/*1C versus *1/*1: 1.89; CI: 0.85-4.22; *1C/*1C versus *1/*1: 4.96; CI: 1.69-14.56; P=0.014). Bleeding events were significantly more common among black carriers of CYP2C19*17 or CYP1A2*1C.Both loss-of-function and gain-of-function CYP polymorphisms affecting clopidogrel metabolism are associated with increased mortality among clopidogrel-treated patients after acute myocardial infarction; the specific polymorphism and the putative mechanism vary according to race.

SUBMITTER: Cresci S

PROVIDER: S-EPMC4104276 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Cytochrome p450 gene variants, race, and mortality among clopidogrel-treated patients after acute myocardial infarction.

Cresci Sharon S Depta Jeremiah P JP Lenzini Petra A PA Li Allie Y AY Lanfear David E DE Province Michael A MA Spertus John A JA Bach Richard G RG

Circulation. Cardiovascular genetics 20140424 3

<h4>Background</h4>Clopidogrel is recommended after acute myocardial infarction but has variable efficacy and safety, in part related to the effect of cytochrome P450 (CYP) polymorphisms on its metabolism. The effect of CYP polymorphisms on cardiovascular events among clopidogrel-treated patients after acute myocardial infarction remains controversial, and no studies to date have investigated the association of CYP variants with outcomes in black patients.<h4>Methods and results</h4>Subjects (27 ...[more]

PMID: 24762860

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Project description:Background Trends in acute myocardial infarction (AMI) incidence rates for diverse races/ethnicities are largely unknown, presenting barriers to understanding the role of race/ethnicity in AMI occurrence. Methods and Results We identified AMI hospitalizations for Kaiser Permanente Southern California members, aged ≥35 years, during 2000 to 2014 using discharge diagnostic codes. We excluded hospitalizations with missing race/ethnicity information. We calculated annual incidence rates (age and sex standardized to the 2010 US census population) for AMI, ST-segment-elevation myocardial infarction, and non-ST-segment-elevation myocardial infarction by race/ethnicity (Hispanic and non-Hispanic racial groups: Asian or Pacific Islander, black, and white). Using Poisson regression, we estimated annual percentage change in AMI, non-ST-segment-elevation myocardial infarction, and ST-segment-elevation myocardial infarction incidence by race/ethnicity and AMI incidence rate ratios between race/ethnicity pairs, adjusting for age and sex. We included 18 630 776 person-years of observation and identified 44 142 AMI hospitalizations. During 2000 to 2014, declines in AMI, non-ST-segment-elevation myocardial infarction, and ST-segment-elevation myocardial infarction were 48.7%, 34.2%, and 69.8%, respectively. Age- and sex-standardized AMI hospitalization rates/100 000 person-years declined for Hispanics (from 307 to 162), Asians or Pacific Islanders (from 271 to 158), blacks (from 347 to 199), and whites (from 376 to 189). Annual percentage changes ranged from -2.99% to -4.75%, except for blacks, whose annual percentage change was -5.32% during 2000 to 2009 and -1.03% during 2010 to 2014. Conclusions During 2000 to 2014, AMI, non-ST-segment-elevation myocardial infarction, and ST-segment-elevation myocardial infarction hospitalization incidence rates declined substantially for each race/ethnic group. Despite narrowing rates among races/ethnicities, differences persist. Understanding these differences can help identify unmet needs in AMI prevention and management to guide targeted interventions.

Dataset Information

Cytochrome p450 gene variants, race, and mortality among clopidogrel-treated patients after acute myocardial infarction.

Publications

Cytochrome p450 gene variants, race, and mortality among clopidogrel-treated patients after acute myocardial infarction.

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