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Effects of aliskiren, a renin inhibitor, on biomarkers of platelet activity, coagulation and fibrinolysis in subjects with multiple risk factors for vascular disease

Journal of Human Hypertension volume 22, pages 303–310 (2008)Cite this article

Abstract

Aliskiren, an octanamide, is nonpeptide, low molecular weight, orally active renin inhibitor effectively preventing angiotensin and aldosterone release. This drug has been recently approved for the treatment of hypertension. Considering potential links between hypertension, platelets, the coagulation cascade and fibrinolysis we sought to evaluate the effect of aliskiren on human biomarkers of hemostasis. In vitro effects of whole blood preincubation with escalating concentrations of aliskiren (500, 1000 and 2000 ng ml−1) were assessed in 20 aspirin-naive volunteers with multiple risk factors for vascular disease. A total of 33 biomarkers were measured, of which 18 are related to platelet function, 12 to coagulation and 3 to fibrinolysis. Pretreatment of blood samples with aliskiren 500 ng ml−1 resulted in a significant increase of antithrombin-III (AT-III) activity (P=0.003). All other tested biomarkers were not significantly affected. Spiking whole blood with the higher aliskiren doses was associated with various trends in biomarker activity, where 1000 ng ml−1 concentration mostly decreased (7/33), and 2000 ng ml−1 mostly increased (6/33) some biomarkers. In the therapeutic concentration of 500 ng ml−1 aliskiren does not affect hemostatic biomarkers, except for a moderate but highly significant (P=0.003) increase of AT-III activity. Higher aliskiren doses were associated with more profound biomarker changes, but they are likely not to be clinically relevant since they show diverging (that is, both mild antiplatelet and platelet-activating) trends, and considering the 2- to 4-fold safety margin. It is suggested that antithrombotic properties of aliskiren be explored further in an ex vivo clinical setting.

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Acknowledgements

We thank all the nurses and laboratory personnel for their technical excellence and outstanding effort in this study. The study was supported in part by a grant from Novartis Pharmaceuticals, East Hanover, NJ, USA. DA was supported by grants from the National Association of Norway for Public Health—the Norwegian Council for Heart and Vessels, the Eastern Regional Health Authority of Norway and the Aker University Hospital Research Foundation.

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Authors and Affiliations

  1. HeartDrug™ Research Laboratories, Johns Hopkins University, Baltimore, MD, USA

    V L Serebruany & A Malinin

  2. Mayo Clinic, Rochester, MN, USA

    G Barsness

  3. Division of Cardiology, Faculty of Medicine, Aker University Hospital, University of Oslo, Oslo, Norway

    J Vahabi & D Atar

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  1. V L Serebruany
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Correspondence to V L Serebruany.

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Serebruany, V., Malinin, A., Barsness, G. et al. Effects of aliskiren, a renin inhibitor, on biomarkers of platelet activity, coagulation and fibrinolysis in subjects with multiple risk factors for vascular disease. J Hum Hypertens 22, 303–310 (2008). https://doi.org/10.1038/jhh.2008.2

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