Novel Antithrombotic Agents in Ischemic Cardiovascular Disease: Progress in the Search for the Optimal Treatment

Abstract

Ischemic cardiovascular diseases have a high incidence and high mortality worldwide. Therapeutic advances in the last decades have reduced cardiovascular mortality, with antithrombotic therapy being the cornerstone of medical treatment. Yet, currently used antithrombotic agents carry an inherent risk of bleeding associated with adverse cardiovascular outcomes and mortality. Advances in understanding the pathophysiology of thrombus formation have led to the discovery of new targets and the development of new anticoagulants and antiplatelet agents aimed at preventing thrombus stabilization and growth while preserving hemostasis. In the following review, we will comment on the key limitation of the currently used antithrombotic regimes in ischemic heart disease and ischemic stroke and provide an in-depth and state-of-the-art overview of the emerging anticoagulant and antiplatelet agents in the pipeline with the potential to improve clinical outcomes.

Keywords: anticoagulants; antiplatelet drugs; cardiovascular diseases; hemostasis; novel antithrombotic agents.

Figure 2

Diagram of the coagulation and fibrinolytic pathways and the different anticoagulants and fibrinolytic agents used in the clinical setting. LMWH: low molecular weight heparin. * Indirect inhibition of factors II, VII, IX and X.

Figure 1

Antiplatelet drugs currently used to treat ischemic heart disease and ischemic stroke. ENT: equilibrative nucleoside transporter; ASA: acetylsalicylic acid; TXA2: thromboxane A2; VWF: Von Willebrand Factor; PDR: phosphodiesterase; COX: cyclooxygenase. Figure created with BioRender.com.

Figure 3

Emerging antiplatelet targets and drugs. PDI: phosphodiesterase; VWF: Von Willebrand factor; GP: glycoprotein; PAR: protease activator receptor.