Platelet inhibition beyond conventional antiplatelet agents: expanding role of angiotensin receptor blockers, statins and selective serotonin reuptake inhibitors

Abstract

Aspirin, dipyridamole, cilostazol, thienopyridines and glycoprotein IIb/IIIa inhibitors represent the classical examples of the established antiplatelet agents commonly used for the secondary prevention in patients after vascular events. Obviously, the era of expanding antiplatelet regimens and indications may require new agents as the substitutes, or additions to the available strategies. However, recent results of the majority of antiplatelet trials strongly suggest boarder line advantages in clinical outcomes, and higher associated bleeding risks with the novel antiplatelet agents or/and regimens. Moreover, unexpected failures, such as lack of efficacy of clopidogrel and aspirin combination for ischaemic stroke prevention (MATCH), or use of the same antiplatelet regimen for the primary vascular prevention (CHARISMA) raise legitimate concerns that the concept 'the more the better' may not be valid. Broad use of statins, angiotensin receptor blockers and selective serotonin reuptake inhibitors may be in part responsible for the lack of impressive results with the antiplatelet therapy because each of these drug classes per se inhibits platelets. In this review, we discuss the available evidence and potential clinical significance of these findings.

Spectrum of Pleiotropic Effects of Statins in Heart Failure

“…[34,35] PAR-1 repression by all statins has been found to be nearly identical. [36] Simvastatin decreases the expression of tissue factor (TF) in a monocyte model of in vitro clotting. When monocytes were treated with LPS and simvastatin, they displayed a decreased rate of thrombin generation by interfering with monocyte expression of TF.…”

Selective serotonin reuptake inhibitors reduce P2Y12 receptor-mediated amplification of platelet aggregation

“…SSRIs block the reuptake of serotonin into neurons as well as platelets. It has been reported that treatment with SSRIs in high dose leads to a remarkable depletion of platelet serotonin level and the attenuation of platelet activation [4], and, subsequently, may exhibit the clinical benefit on the reduction of cardiovascular risk in depression patients with coronary artery disease [5]. Binding of exposed collagen to platelets at the site of vascular injury triggers platelet activation.…”

Clinical importance of aspirin and clopidogrel resistance

“…Their result was in concordance with other studies [24,25] . The broad use of statins, angiotensin receptor blockers and selective serotonin reuptake inhibitors may be, in part, responsible for the lack of agreement [26] . Our previous results showed the effect of different cardiovascular drugs on the laboratory efficacy of aspirin and clopidogrel [27,28] .…”