title: Valsartan inhibits platelet activity at different doses in mild to moderate hypertensives: Valsartan Inhibits Platelets (VIP) trial.
abstract: BACKGROUND
  Previous in vitro studies have suggested that valsartan produces significant inhibition of human platelets, probably targeting angiotensin I platelet receptors. To test whether valsartan inhibits platelet activity in mild to moderate hypertensives we conducted the randomized Valsartan Inhibits Platelets (VIP) trial.
  
  
  RESULTS
  Seventy-five patients with mild to moderate hypertension were randomized to valsartan 80 (n = 25), valsartan 160 (n = 29), or valsartan 320 mg/d (n = 21) for 9 weeks. Platelet function was assessed at baseline, week 5, and week 9 by aggregometry, flow cytometry, and cartridge-based analyzer. Independently of dose and duration, valsartan provided early sustained significant inhibition of adenosine diphosphate-induced platelet aggregation, decreased shear-induced activation measured with PFA-100 analyzer, and diminished expression of GP IIb/IIIa activity measured by PAC-1 antibody, GPIb (CD42b), vitronectin receptor (CD51/61), P-selectin (CD62p), lysosome-associated membrane protein (CD107a), and CD40-ligand (CD154). The antiplatelet properties of valsartan were more profound in patients with diabetes (n = 28) when compared with the nondiabetic group (n = 47). In subgroup analyses of patients with diabetes there appeared to be stronger inhibition of the platelet receptors, a significant decrease of adenosine diphosphate- and collagen-induced platelet aggregation, and more profound inhibition of GP IIb/IIIa activity.
  
  
  CONCLUSIONS
  In the randomized VIP trial, valsartan produced sustained inhibition of platelet aggregation and major platelet receptors. The antiplatelet properties of valsartan were not dose or time dependent. In subgroup analyses patients with diabetes with mild to moderate hypertension tended to have greater platelet inhibition, a finding which, if confirmed in future studies suggests possible additional advantages for using valsartan in this high-risk population.
authors.affiliation: HeartDrug Research Laboratories, Johns Hopkins University, Baltimore, MD, USA. heartdrug@aol.com
authors.forename: Victor L
authors.initials: VL
authors.lastname: Serebruany
authors.forename: Alex N
authors.initials: AN
authors.lastname: Pokov
authors.forename: Alex I
authors.initials: AI
authors.lastname: Malinin
authors.forename: Christopher
authors.initials: C
authors.lastname: O'Connor
authors.forename: Deepak L
authors.initials: DL
authors.lastname: Bhatt
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Tanguay
authors.forename: David C
authors.initials: DC
authors.lastname: Sane
authors.forename: Charles H
authors.initials: CH
authors.lastname: Hennekens
mesh_terms: D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001792:Blood Platelets / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000188:drug therapy*; D008297:Male; D012720:Severity of Illness Index; D013777:Tetrazoles / Q000008:administration & dosage*; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000068756:Valsartan
chemical_list: D000959:Antihypertensive Agents; D013777:Tetrazoles; D000068756:Valsartan; D014633:Valine