Antiplatelet therapy after percutaneous coronary intervention

Abstract

Antiplatelet therapy is key to reducing local thrombotic complications and systemic ischaemic events among patients undergoing percutaneous coronary interventions (PCI), but it is inevitably associated with increased bleeding. The continuous refinement in stent technologies, together with the high incidence of ischaemic recurrences after PCI and the understanding of prognostic implications associated with bleeding, have led to a substantial evolution in antiplatelet treatment regimens over the past decades. Numerous investigations have been conducted to better stratify patients undergoing PCI according to their ischaemic and bleeding risks and to implement antithrombotic regimens accordingly. Evidence from these investigations have resulted in a number of antithrombotic treatment options as recommended by recent guidelines. In this State-of-the-Art review we provide the rationale, summarise the evidence, and discuss current and future directions of antiplatelet treatment regimens after PCI.

Figure 1. Interplay between platelets, coagulation and inflammation in atherothrombosis and sites of action of antiplatelet agents.

The interplay between platelets, coagulation and inflammation is a key modulator of atherosclerosis and its thrombotic complications. When plaque destabilisation occurs, due to plaque rupture or erosion, platelets and coagulation factors, as well as subsequent inflammatory processes, it may lead to either a thrombotic occlusion of the coronary artery (leading to acute coronary syndromes) or plaque healing (favouring plaque progression with stable coronary artery disease). Initial platelet tethering is mediated by the interaction between the complex glycoprotein (GP) Ib-IX-V and Von Willebrand factor (vWF) and by other collagen receptors present on the platelet surface such as GPVI. Thrombin is a key linking factor between platelet and coagulation cascade. Sites of action of common antiplatelet agents are reported: aspirin inhibits thromboxane A2 (TXA2); clopidogrel, prasugrel, ticagrelor and cangrelor are inhibitors of the ADP P2Y₁₂ receptor. Clopidogrel and prasugrel require hepatic activation. Vorapaxar is a thrombin receptor inhibitor (protease-activated receptor, PAR-1); abciximab, eptifibatide, tirofiban and RUC-4 are GPIIb/IIIa receptor inhibitors. Revacept is a competitive antagonist of the collagen-GPVI signalling. Routes of administration: Blue=oral; Green=intravenous; Yellow=subcutaneous/intramuscular. ADP: adenosine diphosphate; GP: glycoprotein; PAR-1: platelet protease-activated receptor-1; TXA2: thromboxane A2; vWF: von Willebrand factor; 5HT2A: serotonine receptor.

Figure 2. Rationale for the use of antiplatelet therapy during PCI.

In patients undergoing PCI in the setting of chronic coronary syndrome (CCS), antiplatelet therapy reduces the occurrence of intraprocedural or very early stent thrombosis (right), periprocedural damage caused by iatrogenic dissections, plaque disruption, distal embolisation or side branch occlusion (middle). During acute coronary syndrome, antiplatelet therapy also plays a role in reducing thrombus burden and flow obstruction (left). PCI: percutaneous coronary intervention.

Figure 3. Time course of benefit and risk of antiplatelet therapy after PCI.

Antiplatelet agents administered after PCI may 1) reduce the incidence of stent-related ischaemic events such as stent thrombosis or target vessel revascularisation; 2) reduce the incidence of cardiovascular ischaemic recurrence and their consequences, such as myocardial infarction and cardiovascular death; 3) prevent cerebrovascular events in other areas affected by atherosclerotic disease, such as peripheral and carotid arteries; 4) be inevitably associated with increased risk of bleeding. Importantly, the potential benefit of antiplatelet agents varies over time, with the greatest benefit in terms of less ischaemic events maximised during the first months after PCI and decreasing over time, while bleeding events remain stable over time. DAPT: dual antiplatelet therapy; PCI: percutaneous coronary intervention.

Figure 4. Current Guidelines of the European Society of Cardiology recommendations for oral antiplatelet agents among patients undergoing PCI.

DAPT: dual antiplatelet therapy; DPI: dual pathway inhibition; NSTE-ACS: non-ST-elevation acute coronary syndrome; PCI: percutaneous coronary intervention; STE-ACS: ST segment-elevation acute coronary syndrome

Figure 5. Risk assessment to guide antiplatelet therapy among percutaneous coronary disease patients.

Bleeding and ischaemic risk assessments are based on clinical variables, procedural features and the use of scores/definitions. Antiplatelet responsiveness can be assessed by either platelet function or genetic testing. BMI: body mass index; CTO: chronic total occlusion; GP: glycoprotein; MI: myocardial infarction; PCI: percutaneous coronary intervention; ST: stent thrombosis.

Central illustration. Timeline of randomised controlled trials on antiplatelet therapy focusing on strategies aiming at reducing ischaemic (upper) or bleeding (lower) events.

DAPT: dual antiplatelet therapy