Cor Vasa 2013, 55(2):e86-e94 | DOI: 10.1016/j.crvasa.2013.03.003

Antiplatelet therapy - a pharmacologist's perspective

Jan Bultas

Ústav farmakologie, 3. lékařská fakulta Univerzity Karlovy, Praha, Česká republika

There are only few areas of cardiology that have witnessed such dramatic innovations as that occurring in the treatment and prophylaxis of thrombotic events. Antithrombotic (i.e., antiplatelet and anticoagulation) therapy plays a pivotal role in the prophylaxis of the pandemic of cardiovascular disease. Given the host of triggers activating primary hemostasis, various therapeutic strategies are currently available. The current approach, monotherapy or dual therapy or, possibly, combination therapy with antiplatelet and anticoagulant agents is selected based on the risk of a thrombotic event, dominant disease, and the risk of bleeding.
The main problem associated with the current therapeutic strategy was not an insufficient effect, but major inter-individual variability of effect resulting in therapy failure or an unacceptable risk of bleeding documented in a non-negligible proportion of patients. Hence the drive for devising new antiplatelet strategies and innovation in (already) established classes of drugs.
Milestones in the evolution of antiplatelet therapy included the advent of new, more effective and/or safer antiplatelet agents inhibiting platelet activation. The new irreversible P2Y12 receptor antagonist prasurgel and rever-sible P2Y12 receptor antagonist ticagrelor have been approved for clinical use. There has also been major progress in the development of thrombin protease-activated receptor 1 (PAR-1) antagonists (vorapaxar, atopaxar) or serotonin receptor blockers (sarpogrelat). Another promising therapeutic strategy is targeted at platelet stabilization through increased cyclic adenosine monophosphate (cAMP) activity by platelet phosphodiesterase-3 inhibition (cilostazol). Further, new insights into the bioavailability of acetylsalicylic acid under specific conditions have been reported regarding the class of agents inhibiting thromboxane A2-mediated activation.

Keywords: ADP receptor P2Y12 inhibitors; Antiplatelet agents; GP IIb, IIIa receptor inhibitors; 5-HT receptor inhibitors; PAR-1 inhibitors; TXA2 synthesis inhibitors

Received: January 29, 2013; Revised: March 5, 2013; Accepted: March 6, 2013; Published: April 1, 2013  Show citation