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The Impact of Obesity and Diabetes on Clopidogrel Resistance in Transcarotid Artery Revascularization Patients
Benjamin B Samberg, Emily D Burnett, Thomas A Cook, Jacob A Hoffman, Gear T Vincent, Nicholas Bandy, Jean Panneton, Hosam F El Sayed
Eastern Virginia Medical School, Norfolk, VA
INTRODUCTION: Clopidogrel is an FDA approved medication for treatment of many cardiovascular thrombolytic deficits. Its therapeutic effect is mediated through the irreversible inhibition of the platelet P2Y12 adenosine diphosphate receptor, inhibiting platelet aggregation. Clopidogrel is an inactive prodrug and is activated through metabolization by liver enzymes of the cytochrome p450 (CYP) family. Clopidogrel resistance (CR) has been observed in diabetic and obese patients through downregulation of CYP enzymes. This study aims to evaluate the observed CR rate in patients undergoing Transcarotid Artery Revascularization (TCAR) as well as determining the impact BMI and diabetes status have on CR rates. Other variables will also be evaluated for their association with CR.
METHODS: Patients ≥ 18 years who underwent TCAR with perioperative platelet reactivity testing between April 2016 and December 2023 were identified across four institutions. Platelet reactivity was measured with the VerifyNow P2Y12 Reaction Unit (PRU) Test (Instrumentation Laboratory, Bedford, MA), with CR defined as PRU ≥ 180. This study was performed via nonrandomized, nonblinded retrospective chart review of TCAR patients treated at the selected medical centers. Data concerning medications, comorbidities, perioperative events, and mortality were collected.
RESULTS: Out of 469 TCAR patients, 134 (28.6%) were identified with associated P2Y12 values for inclusion in this study. Of the 134 patients included, the majority were male (59.7%) and Caucasian (82.8%), with a mean age of 72.4 years (±9, range 52-91). Perioperatively, 94.0% of patients were on aspirin and 89.6% on clopidogrel. At presentation, 58.2% had symptomatic carotid stenosis. The mean perioperative P2Y12 was 151 PRU (±78, range 2-367). In total, 50 (37.3%) patients met criteria for CR (mean PRU 231± 41; range 181-367). Analysis of these 134 patients found that diagnoses of obesity (p = 0.686), hypertension (p = 0.854), hyperlipidemia (p = 0.790), hypercholesterolemia (p = 0.378), and smoking status (p = 0.416) were not statistically significant indicators of CR status. There was however a significant association between CR and patient diabetic status: patients diagnosed with diabetes (type 1 or type 2) were over two times more likely to have CR than those who were not diagnosed with diabetes (OR = 2.23, p = 0.047). Women were also over two times more likely to have CR than men (OR = 2.23, p = 0.043). There was also a significant difference in the ages of patients based on CR status (p = 0.045), with resistant patients (𝜇;; = 74.5±9, range 52-89) being older than non-resistant patients (𝜇;; = 71.2±9, range 52-91).
CONCLUSIONS: Of the 134 TCAR who received P2Y12 testing, 37.3% were found to have clopidogrel resistance. Diabetes and female sex were associated with significantly higher rates of CR, and CR was associated with significantly higher patient age. Other evaluated comorbidities, including obesity, were not significant variables impacting CR. These data suggest a possible benefit to routine P2Y12 testing in the TCAR population, especially so in older, diabetic and female patients. Further research is warranted to examine the link between CR status and these variables.
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