Antiplatelet effects of aspirin are not affected by the soluble guanylate cyclase activator cinaciguat (BAY 58-2667)

Introduction Cinaciguat (BAY 58-2667) is an nitric oxide (NO)-independent and heme-independent soluble guanylate cyclase (sGC) activator. Cinaciguat preferentially activates sGC in its oxidized or heme-free state, when the enzyme is insensitive to its endogenous ligand NO and exogenous nitrovasodilators [1]. Endothelium-derived NO is one of the mechanisms by which platelet aggregation and thrombus formation is prevented by the intact blood vessel wall. Pharmacological stimulation of sGC in platelets correlates with inhibition of aggregation, platelet cGMP increase, prolongation of bleeding time and antithrombotic effects in vitro [2]. This protective mechanism may be impaired in vascular disease and impaired NO availability. Thus, sGC activators may have antithrombotic effects similar to endogenous NO. Indeed, cinaciguat potently inhibited platelet aggregation induced by the thromboxane mimic U46619 and collagen and prolonged rat-tail bleeding time up to 2-fold [3]. Thus, in vitro data suggested that coadministration of cinaciguat and aspirin may increase the antiplatelet effects of aspirin and could result in bleeding.