TY - JOUR
T1 - Enteric Coating and Aspirin Nonresponsiveness in Patients With Type 2 Diabetes Mellitus
AU - Bhatt, Deepak L.
AU - Grosser, Tilo
AU - Dong, Jing fei
AU - Logan, Douglas
AU - Jeske, Walter
AU - Angiolillo, Dominick J.
AU - Frelinger, Andrew L.
AU - Lei, Lanyu
AU - Liang, Juan
AU - Moore, Jason E.
AU - Cryer, Byron
AU - Marathi, Upendra
N1 - Publisher Copyright:
© 2017 American College of Cardiology Foundation
PY - 2017/2/14
Y1 - 2017/2/14
N2 - Background A limitation of aspirin is that some patients, particularly those with diabetes, may not have an optimal antiplatelet effect. Objectives The goal of this study was to determine if oral bioavailability mediates nonresponsiveness. Methods The rate and extent of serum thromboxane generation and aspirin pharmacokinetics were measured in 40 patients with diabetes in a randomized, single-blind, triple-crossover study. Patients were exposed to three 325-mg aspirin formulations: plain aspirin, PL2200 (a modified-release lipid-based aspirin), and a delayed-release enteric-coated (EC) aspirin. Onset of antiplatelet activity was determined by the rate and extent of inhibition of serum thromboxane B2 (TXB2) generation. Aspirin nonresponsiveness was defined as a level of residual serum TXB2 associated with elevated thrombotic risk (<99.0% inhibition or TXB2 >3.1 ng/ml) within 72 h after 3 daily aspirin doses. Results The rate of aspirin nonresponsiveness was 15.8%, 8.1%, and 52.8% for plain aspirin, PL2200, and EC aspirin, respectively (p < 0.001 for both comparisons vs. EC aspirin; p = 0.30 for comparison between plain aspirin and PL2200). Similarly, 56% of EC aspirin–treated subjects had serum TXB2 levels >3.1 ng/ml, compared with 18% and 11% of subjects after administration of plain aspirin and PL2200 (p < 0.0001). Compared with findings for plain aspirin and PL2200, this high rate of nonresponsiveness with EC aspirin was associated with lower exposure to acetylsalicylic acid (63% and 70% lower geometric mean maximum plasma concentration [Cmax] and 77% and 82% lower AUC0–t [area under the curve from time 0 to the last time measured]) and 66% and 72% lower maximum decrease of TXB2, with marked interindividual variability. Conclusions A high proportion of patients treated with EC aspirin failed to achieve complete inhibition of TXB2 generation due to incomplete absorption. Reduced bioavailability may contribute to “aspirin resistance” in patients with diabetes.
AB - Background A limitation of aspirin is that some patients, particularly those with diabetes, may not have an optimal antiplatelet effect. Objectives The goal of this study was to determine if oral bioavailability mediates nonresponsiveness. Methods The rate and extent of serum thromboxane generation and aspirin pharmacokinetics were measured in 40 patients with diabetes in a randomized, single-blind, triple-crossover study. Patients were exposed to three 325-mg aspirin formulations: plain aspirin, PL2200 (a modified-release lipid-based aspirin), and a delayed-release enteric-coated (EC) aspirin. Onset of antiplatelet activity was determined by the rate and extent of inhibition of serum thromboxane B2 (TXB2) generation. Aspirin nonresponsiveness was defined as a level of residual serum TXB2 associated with elevated thrombotic risk (<99.0% inhibition or TXB2 >3.1 ng/ml) within 72 h after 3 daily aspirin doses. Results The rate of aspirin nonresponsiveness was 15.8%, 8.1%, and 52.8% for plain aspirin, PL2200, and EC aspirin, respectively (p < 0.001 for both comparisons vs. EC aspirin; p = 0.30 for comparison between plain aspirin and PL2200). Similarly, 56% of EC aspirin–treated subjects had serum TXB2 levels >3.1 ng/ml, compared with 18% and 11% of subjects after administration of plain aspirin and PL2200 (p < 0.0001). Compared with findings for plain aspirin and PL2200, this high rate of nonresponsiveness with EC aspirin was associated with lower exposure to acetylsalicylic acid (63% and 70% lower geometric mean maximum plasma concentration [Cmax] and 77% and 82% lower AUC0–t [area under the curve from time 0 to the last time measured]) and 66% and 72% lower maximum decrease of TXB2, with marked interindividual variability. Conclusions A high proportion of patients treated with EC aspirin failed to achieve complete inhibition of TXB2 generation due to incomplete absorption. Reduced bioavailability may contribute to “aspirin resistance” in patients with diabetes.
KW - acetylsalicylic acid
KW - enteric coating
KW - pharmacodynamics
KW - pharmacokinetics
KW - platelet function
KW - thromboxane
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U2 - 10.1016/j.jacc.2016.11.050
DO - 10.1016/j.jacc.2016.11.050
M3 - Article
C2 - 28089180
AN - SCOPUS:85009738472
SN - 0735-1097
VL - 69
SP - 603
EP - 612
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 6
ER -