Prevalence and Clinical Predictors of Aspirin Resistance in Heart Transplant Recipients

Abstract

Enhanced platelet activation is strongly associated with the development and progression of transplant vasculopathy. Aspirin is thought to be associated with improved graft survival and reduced cardiac allograft vasculopathy in heart transplant (HT) recipients. The assessment of aspirin resistance by laboratory methods is potentially of great therapeutic importance, as it would enable identification of patients at risk for clinical events and allow intervention to prevent subsequent morbidity or mortality. We aimed to determine the prevalence and clinical predictors of aspirin resistance following HT. We evaluated 67 stable HT recipients receiving antiplatelet monotherapy with aspirin (100 mg/day≥1 month). Platelets were stimulated with adenosine diphosphate (ADP) and arachidonic acid (AA), and aggregation was assessed using light-transmitted aggregometry. Aggregation was expressed as the maximal percent change in light transmittance from baseline. Aspirin resistance was defined as AA-induced platelet aggregation of ≥20%. Mean AA-induced aggregation was 29.6 ±24.8%. Of the total cohort, 40 patients (60%) were aspirin resistant and 27 (40%) were not. Aspirin-resistant patients had higher HbA1c values (7.7%±1.5 vs 5.3%±0.9, p<0.001) and higher prevalence of de novo donor-specific antibodies (DSA) (43 vs 11%, p=0.013). There were no differences in aspirin resistance by baseline donor and recipient characteristics (i.e., age, gender, etiology, BMI, hypertension, hemodynamics, immunosuppression). In a multivariable analysis (Figure) HbA1c and DSA were independently associated with a significantly higher risk of aspirin resistance. Our study suggests a high rate of aspirin resistance in HT patients, which was associated with higher DSA and HbA1c levels, both known risk factors for transplant vasculopathy and survival. Further studies are needed to correlate aspirin resistance with clinical outcomes and hence to tailor therapeutic interventions.