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), lyso-some-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.
| Original language | English |
|---|---|
| Pages (from-to) | 482-490 |
| Number of pages | 9 |
| Journal | American Journal of Therapeutics |
| Volume | 21 |
| Issue number | 6 |
| Publication status | Published - Dec 4 2014 |
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Keywords
- Aliskiren
- Clinical trial
- Diabetes
- Hemostasis
- Valsartan
ASJC Scopus subject areas
- Pharmacology
- Pharmacology (medical)
- Medicine(all)
Cite this
Effect of aliskiren and valsartan combination versus aliskiren monotherapy on hemostatic biomarkers in hypertensive diabetics : Aliskiren and valsartan impact in diabetics pilot trial. / Serebruany, Victor L.; Pokov, Alex N.; Aradi, D.; Can, Mehmet; DiNicolantonio, James; Kipshidze, Nodar; Atar, Dan.
In: American Journal of Therapeutics, Vol. 21, No. 6, 04.12.2014, p. 482-490.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Effect of aliskiren and valsartan combination versus aliskiren monotherapy on hemostatic biomarkers in hypertensive diabetics
T2 - Aliskiren and valsartan impact in diabetics pilot trial
AU - Serebruany, Victor L.
AU - Pokov, Alex N.
AU - Aradi, D.
AU - Can, Mehmet
AU - DiNicolantonio, James
AU - Kipshidze, Nodar
AU - Atar, Dan
PY - 2014/12/4
Y1 - 2014/12/4
N2 - 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), lyso-some-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.
AB - 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), lyso-some-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.
KW - Aliskiren
KW - Clinical trial
KW - Diabetes
KW - Hemostasis
KW - Valsartan
UR - http://www.scopus.com/inward/record.url?scp=84914155363&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84914155363&partnerID=8YFLogxK
M3 - Article
C2 - 23698186
AN - SCOPUS:84914155363
VL - 21
SP - 482
EP - 490
JO - American Journal of Therapeutics
JF - American Journal of Therapeutics
SN - 1075-2765
IS - 6
ER -