title: Effect of aliskiren and valsartan combination versus aliskiren monotherapy on hemostatic biomarkers in hypertensive diabetics: Aliskiren and Valsartan Impact in Diabetics pilot trial.
abstract: 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.
authors.affiliation: 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.
authors.forename: Victor L
authors.initials: VL
authors.lastname: Serebruany
authors.forename: Alex N
authors.initials: AN
authors.lastname: Pokov
authors.forename: Daniel
authors.initials: D
authors.lastname: Aradi
authors.forename: Mehmet
authors.initials: M
authors.lastname: Can
authors.forename: James
authors.initials: J
authors.lastname: DiNicolantonio
authors.forename: Nodar
authors.initials: N
authors.lastname: Kipshidze
authors.forename: Dan
authors.initials: D
authors.lastname: Atar
mesh_terms: D000577:Amides / Q000008:administration & dosage / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001241:Aspirin / Q000008:administration & dosage; D015415:Biomarkers / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005650:Fumarates / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D013777:Tetrazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000068756:Valsartan; D000092502:Renin Inhibitors
chemical_list: D000577:Amides; D000959:Antihypertensive Agents; D001241:Aspirin; D015415:Biomarkers; D005650:Fumarates; D013777:Tetrazoles; D014633:Valine; D000068756:Valsartan; D000092502:Renin Inhibitors; C446481:aliskiren