Dual antiplatelet therapy for secondary prevention of coronary artery disease

Abstract

Dual antiplatelet therapy (DAPT) combining aspirin and a P2Y₁₂ receptor inhibitor has been consistently shown to reduce recurrent major adverse cardiovascular events (MACE) in patients with acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI) for stable coronary artery disease (CAD) compared with aspirin monotherapy, but at the expense of an increased risk of major bleeding. Nevertheless, the optimal duration of DAPT for secondary prevention of CAD remains uncertain, owing to the conflicting results of several large randomised trials. Among patients with stable CAD undergoing PCI with drug-eluting stents (DES), shorter durations of DAPT (3-6 months) were shown non-inferior to 12 or 24 months duration with respect to MACE, but reduced the rates of major bleeding. Contrariwise, prolonged DAPT durations (18-48 months) reduced the incidence of myocardial infarction and stent thrombosis, but at a cost of an increased risk of major bleeding and all-cause mortality. Until more evidence becomes available, the choice of optimal DAPT regimen and duration for patients with CAD requires a tailored approach based on the patient clinical presentation, baseline risk profile and management strategy. Future studies are however needed to identify patients who may derive benefit from shortened or extended DAPT courses for secondary prevention of CAD based on their individual ischaemic and bleeding risk. Based on limited evidence, 12 months duration of DAPT is currently recommended in patients with ACS irrespective of their management strategy, but large ongoing randomised trials are currently assessing the efficacy and safety of a short-term DAPT strategy (3-6 months) for patients with ACS undergoing PCI with newer generation DES. Finally, several ongoing, large-scale, randomised trials are challenging the current concept of DAPT by investigating P2Y₁₂ receptor inhibitors as single antiplatelet therapy and may potentially shift the paradigm of antiplatelet therapy after PCI in the near future. This article provides a contemporary state-of-the-art review of the current evidence on DAPT for secondary prevention of patients with CAD and its future perspectives.

Keywords: antiplatelet therapy; coronary artery disease.

Figure 1

P2Y₁₂ receptor inhibitor therapy for secondary prevention of patients with stable coronary artery disease. BMS, bare metal stent; CABG, coronary artery bypass graft surgery; CV, cardiovascular; DAPT, dual antiplatelet therapy; DES, drug-eluting stent; MI, myocardial infarction; PCI, percutaneous coronary intervention.

Figure 2

P2Y₁₂ receptor inhibitor therapy for secondary prevention of patients with acute coronary syndrome. BMS, bare metal stent; CABG, coronary artery bypass graft surgery; DAPT, dual antiplatelet therapy; DES, drug-eluting stent; PCI, percutaneous coronary intervention.

Figure 3

Antithrombotic strategies in patients on long-term oral anticoagulation therapy undergoing percutaneous coronary intervention. ACS: acute coronary syndrome; NOAC: non-vitamin K antagonist oral anticoagulant; PCI: percutaneous coronary intervention; OAC: oral anticoagulation; SCAD: stable coronary artery disease; VKA: vitamin K antagonist. ^aDual therapy with oral anticoagulation and single antiplatelet therapy (aspirin or clopidogrel) may be considered in selected patients at low ischaemic risk. ^bDual antiplatelet therapy (aspirin and clopidogrel) may be considered. ^cDual therapy with oral anticoagulation and aspirin (as an alternative to clopidogrel) may be considered. ^dDual therapy with oral anticoagulation and single antiplatelet therapy (aspirin or clopidogrel) up to 12 months may be considered in selected patients, particularly for patients managed medically or undergoing CABG. ^eDual therapy with oral anticoagulation and a single antiplatelet agent (aspirin or clopidogrel) may be considered in patients at very high risk of coronary events. ^fDual therapy with oral anticoagulation and clopidogrel may be considered in selected patients at low ischaemic risk. ^gTriple therapy with oral anticoagulation and dual antiplatelet therapy (aspirin and clopidogrel) may be considered up to 12 months in very selected patients at high risk of ischaemic events: prior stent thrombosis on adequate antiplatelet therapy, left main coronary artery or last remaining patent coronary artery stenting, multiple stenting in proximal coronary artery segments, two stents bifurcation treatment, or diffuse multivessel coronary artery disease, particularly in patients with diabetes mellitus. ^hChoice and dose of oral anticoagulants used in combination with antiplatelet therapy: Vitamin K antagonist (International Normalised Ratio 2-2,5); Dabigatran 110 mg once daily; Rivaroxaban 15 mg once daily; Apixaban 2,5 mg twice daily; Edoxaban 30 mg (or 15 mg) once daily.

Figure 4

P2Y₁₂ receptor inhibitor therapy for secondary prevention of patients with coronary artery disease. BMS, bare metal stent; CABG, coronary artery bypass graft surgery; DAPT, dual antiplatelet therapy; DES, drug-eluting stent; MI, myocardial infarction; PCI, percutaneous coronary intervention.