Serebruany Victor L, Pokov Alex N, Aradi Daniel, Can Mehmet, DiNicolantonio James, Kipshidze Nodar, Atar Dan
1HeartDrug Research Laboratories, Johns Hopkins University, Baltimore, MD; 2Heart Institute, University of Pécs, Pécs, Hungary; 3Wegmans Pharmacy, Ithaca, NY; 4Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway; and 5Institute for Clinical Medicine, University of Oslo, Oslo, Norway.
Am J Ther. 2014 Nov-Dec;21(6):482-90. doi: 10.1097/MJT.0b013e31826915ab.
Valsartan is known to inhibit platelet activity in both in vitro and ex vivo clinical setting, whereas aliskiren in vitro modulates antithrombin-III in plasma. The authors tested how aliskiren and valsartan combination versus aliskiren monotherapy will affect hemostatic biomarkers in mild-to-moderate hypertensive diabetics in the frame of the Aliskiren and Valsartan Impact in Diabetics (AVID) trial. A total of 52 patients with type 2 diabetes and mild-to-moderate hypertension were equally randomized to aliskiren (150-300 mg/d) and valsartan (160 mg/d) versus aliskiren (150-300 mg/d) alone for 4 weeks. A total of 25 biomarkers were serially measured, of which 16 are related to platelet function, 6 to coagulation, and 3 to fibrinolysis. Aliskiren monotherapy has no significant impact on any of the assessed biomarkers. In contrast, valsartan on top of aliskiren provided significant inhibition of ADP-induced platelet aggregation (P=0.032), decreased shear-induced activation measured with PFA-100 analyzer (P=0.041), and diminished expression of GP IIb/IIIa activity (P=0.027) measured by PAC-1 antibody, GP Ib (CD42b, P=0.033), vitronectin receptor (CD51/61, P=0.046), P-selectin (CD62p, P=0.026), lysosome-associated membrane protein (CD107a, P=0.042), and CD40-ligand (CD154, P=0.048). In AVID trial, valsartan in combination with aliskiren mildly but significantly inhibited platelets, confirming previous observations. In contrast, aliskiren monotherapy does not enhance antithrombin activity, suggesting that previous data probably represent a laboratory artifact. Importantly, these randomized data were generated on top of low-dose daily aspirin, supporting extra benefit for combination use of angiotensin receptor blockers and renin inhibitors in high-risk diabetic population.
已知缬沙坦在体外和离体临床环境中均能抑制血小板活性，而阿利吉仑在体外可调节血浆中的抗凝血酶III。作者在阿利吉仑和缬沙坦对糖尿病患者的影响（AVID）试验框架内，测试了阿利吉仑与缬沙坦联合用药与阿利吉仑单药治疗相比，对轻度至中度高血压糖尿病患者止血生物标志物的影响。总共52例2型糖尿病合并轻度至中度高血压患者被平均随机分为阿利吉仑（150 - 300mg/d）联合缬沙坦（160mg/d）组和阿利吉仑（150 - 300mg/d）单药组，治疗4周。连续测量了总共25种生物标志物，其中16种与血小板功能有关，6种与凝血有关，3种与纤维蛋白溶解有关。阿利吉仑单药治疗对任何评估的生物标志物均无显著影响。相比之下，在阿利吉仑基础上加用缬沙坦可显著抑制ADP诱导的血小板聚集（P = 0.032），降低用PFA - 100分析仪测量的剪切诱导活化（P = 0.041），并减少通过PAC - 1抗体测量的GP IIb/IIIa活性表达（P = 0.027）、GP Ib（CD42b，P = 0.033）、玻连蛋白受体（CD51/61，P = 0.046）、P - 选择素（CD62p，P = 0.026）、溶酶体相关膜蛋白（CD107a，P = 0.042）和CD40配体（CD154，P = 0.048）。在AVID试验中，缬沙坦与阿利吉仑联合用药对血小板有轻度但显著的抑制作用，证实了先前的观察结果。相比之下，阿利吉仑单药治疗并未增强抗凝血酶活性，这表明先前的数据可能是实验室假象。重要的是，这些随机数据是在低剂量每日阿司匹林基础上产生的，支持了血管紧张素受体阻滞剂和肾素抑制剂联合使用对高危糖尿病患者的额外益处。
