Dual Antiplatelet Therapy: A Concise Review for Clinicians

Abstract

Dual antiplatelet therapy (DAPT) combines two antiplatelet agents to decrease the risk of thrombotic complications associated with atherosclerotic cardiovascular diseases. Emerging data about the duration of DAPT is being published continuously. New approaches are trying to balance the time, benefits, and risks for patients taking DAPT for established cardiovascular diseases. Short-term dual DAPT of 3-6 months, or even 1 month in high-bleeding risk patients, is equivalent in terms of efficacy and effectiveness compared to long-term DAPT for patients who experienced percutaneous coronary intervention in an acute coronary syndrome setting. Prolonged DAPT beyond 12 months reduces stent thrombosis, major adverse cardiovascular events, and myocardial infarction rates but increases bleeding risk. Extended DAPT does not significantly benefit stable coronary artery disease patients in reducing stroke, myocardial infarction, or cardiovascular death. Ticagrelor and aspirin reduce cardiovascular events in stable coronary artery disease with diabetes but carry a higher bleeding risk. Antiplatelet therapy duration in atrial fibrillation patients after percutaneous coronary intervention depends on individual characteristics and bleeding risk. Antiplatelet therapy is crucial for post-coronary artery bypass graft and transcatheter aortic valve implantation; Aspirin (ASA) monotherapy is preferred. Antiplatelet therapy duration in peripheral artery disease depends on the scenario. Adding vorapaxar and cilostazol may benefit secondary prevention and claudication, respectively. Carotid artery disease patients with transient ischemic attack or stroke benefit from antiplatelet therapy and combining ASA and clopidogrel is more effective than ASA alone. The optimal duration of DAPT after carotid artery stenting is uncertain. Resistance to ASA and clopidogrel poses an incremental risk of deleterious cardiovascular events and stroke. The selection and duration of antiplatelet therapy in patients with cardiovascular disease requires careful consideration of both efficacy and safety outcomes. The use of combination therapies may provide added benefits but should be weighed against the risk of bleeding. Further research and clinical trials are needed to optimize antiplatelet treatment in different patient populations and clinical scenarios.

Keywords: DAPT; dual antiplatelet therapy.

Figure 1

Antiplatelet therapy. Mechanisms of action. (A) Aspirin irreversibly inhibits the enzyme cyclooxygenase-1 (COX-1), reducing the formation of thromboxane A2 and effectively inhibiting platelet aggregation. Indobufen also inhibits COX-1, but as a reversible inhibitor. (B) Cilostazol inhibits phosphodiesterase type 3 (PDE3), leading to increased levels of intracellular cyclic adenosine 3′,5′-monophosphate (cAMP) in platelets and vascular smooth muscle cells. This results in the inhibition of platelet aggregation and peripheral arterial vasodilation. Dipyridamole, on the other hand, acts as a phosphodiesterase inhibitor, increasing cAMP levels and exerting vasodilatory and antiplatelet effects. Additionally, dipyridamole inhibits the uptake of adenosine by platelets and other tissues, leading to increased extracellular adenosine concentration. (C) Ticagrelor directly acts on the P2Y12 receptor as a reversible inhibitor, preventing platelet aggregation and receptor-mediated activation. (D) Clopidogrel blocks the P2Y12 receptor on the surface of platelets, thereby inhibiting platelet aggregation and P2Y12-mediated activation. Prasugrel selectively inhibits the P2Y12 receptor on platelets, effectively blocking platelet aggregation and reducing the formation of blood clots. (E) Vorapaxar functions as an inhibitor of the protease-activated receptor-1 (PAR-1), reducing platelet response to thrombin and consequently decreasing blood clot formation.

Figure 2

DAPT recommendations according to the intervention approach and bleeding risk. DAPT is not indicated for patients with stable CAD undergoing medical therapy alone or CABG as a treatment option. Abbreviations: ACS: Acute Coronary Syndrome; CABG: Coronary Artery Bypass Graft; DAPT: Dual Antiplatelet Therapy; PCI: Percutaneous Coronary Intervention; Stable CAD: Stable Coronary Artery Disease.