Tanaka Atsushi, Kawaguchi Atsushi, Oyama Jun-Ichi, Ishizu Tomoko, Ito Hiroshi, Fukui Jun, Kondo Taizo, Kuroki Shigetaka, Nanasato Mamoru, Higashi Yukihito, Kaku Kohei, Inoue Teruo, Murohara Toyoaki, Node Koichi
Department of Cardiovascular Medicine, Saga University, Saga, Japan.
Clinical Research Center, Saga University, Saga, Japan.
Heart Vessels. 2019 Feb;34(2):375-384. doi: 10.1007/s00380-018-1275-5. Epub 2018 Oct 3.
Accumulated evidence shows that some antidiabetic agents attenuate the progression of carotid atherosclerosis assessed as intima-media thickness (IMT). Although some studies have demonstrated an inhibitory effect of dipeptidyl peptidase-4 inhibitors on carotid IMT progression, in the PROLOGUE study sitagliptin failed to slow progression relative to conventional therapy for 24 months. We hypothesized that differences in the concomitant antidiabetic agents between the groups have influenced the progression of carotid IMT. We performed a post hoc analysis of the PROLOGUE study using subgroups stratified by concomitant antidiabetic agents. Although no subgroup with any combination of agents in the overall patients showed a significant difference between sitagliptin group and conventional therapy group in the changes from baseline in mean common carotid artery (CCA)-IMT at 24 months, a significant attenuation of mean CCA-IMT progression was observed in the sitagliptin group relative to conventional therapy group only in three combination subgroups aged < 70 years, namely no thiazolidinedione; no thiazolidinedione or biguanide; and no thiazolidinedione, biguanide or α-glucosidase inhibitor, even after adjustment for multiple confounding factors. In the three subgroups, no significant difference between sitagliptin group and conventional therapy group in the changes from baseline in HbA1c at 24 months was detected. Our data suggest that some concomitant agents, whose prescription frequencies were increased in the conventional therapy group, may have masked the inhibitory effect of sitagliptin on carotid IMT progression in the PROLOGUE study.
越来越多的证据表明，一些抗糖尿病药物可减缓以颈动脉内膜中层厚度（IMT）评估的颈动脉粥样硬化进展。尽管一些研究已证实二肽基肽酶-4抑制剂对颈动脉IMT进展具有抑制作用，但在PROLOGUE研究中，与传统治疗相比，西他列汀在24个月内未能减缓进展。我们推测，两组之间联合使用的抗糖尿病药物差异影响了颈动脉IMT的进展。我们使用按联合使用的抗糖尿病药物分层的亚组对PROLOGUE研究进行了事后分析。尽管在总体患者中，任何药物组合的亚组在24个月时，西他列汀组和传统治疗组之间的平均颈总动脉（CCA）-IMT相对于基线的变化均未显示出显著差异，但仅在年龄<70岁的三个联合亚组中，即未使用噻唑烷二酮；未使用噻唑烷二酮或双胍；以及未使用噻唑烷二酮、双胍或α-葡萄糖苷酶抑制剂，即使在对多个混杂因素进行调整后，相对于传统治疗组，西他列汀组仍观察到平均CCA-IMT进展显著减缓。在这三个亚组中，未检测到西他列汀组和传统治疗组在24个月时HbA1c相对于基线的变化有显著差异。我们的数据表明，在PROLOGUE研究中，传统治疗组中处方频率增加的一些联合用药可能掩盖了西他列汀对颈动脉IMT进展的抑制作用。
