In the first series of patients receiving a bare metal stent (BMS), stent thrombosis was already recognized as a severe complication after implantation owing to its high mortality. With the introduction of P2Y-receptor antagonists (that is, ticlopidine, clopidogrel) for platelet inhibition in combination with acetylsalicylic acid (ASA), the incidence of stent thrombosis decreased substantially in stable patients to levels as low as 1% . Randomized controlled trials have established the efficacy of clopidogrel therapy following hospitalization in patients with acute coronary syndrome (ACS) that were treated either medically or with percutaneous coronary intervention (PCI) [2–4]. The implantation of drug-eluting stents (DES) has become a standard treatment for the management of patients with coronary artery disease. The widespread use of DES has significantly reduced the risk for in-stent restenosis compared to BMS [5, 6]. However, there is some concern that DES might be associated with high rates of stent thrombosis, particularly beyond the first year after implantation . The dominant risk factor for the occurrence of late stent thrombosis is discontinuation of antiplatelet therapy, including aspirin and thienopyridines (clopidogrel and prasugrel). Late stent thrombosis occurs within the first year after implantation of a DES [8–13]. It remains unknown whether it might be advantageous to prolong the 12-month antiplatelet thienopyridine (clopidogrel) therapy after DES implantation.
A recent update of the guidelines for PCI from the American College of Cardiology/American Heart Association/Society of Cardiovascular Angiography and Interventions stressed that all patients that receive a DES should be given clopidogrel treatment for at least 12 months in the absence of increased risk of bleeding . Interestingly, the European Society of Cardiology guidelines on PCI differ slightly; they recommend clopidogrel therapy for 6 to 12 months after implantation of a DES, and for 9 to 12 months when a stenting procedure follows a presentation of an acute coronary syndrome (ACS) .
Early observational studies have suggested that extended use of clopidogrel in patients with a DES may be associated with reduced risk of death and myocardial infarction (MI) . Additional studies have observed a clustering of adverse events in the initial 90 days after discontinuation of clopidogrel; this suggested the possibility of a clopidogrel rebound effect . Based on those results, and also taking into account results from the Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) study, some experts have advocated indefinite clopidogrel therapy . However, when considering the potential beneficial effects of dual antiplatelet therapy, it is important to be aware that extending dual antiplatelet therapy beyond one year may induce bleeding complications. A meta-analysis of dual antiplatelet therapy has shown that this combination, compared to aspirin alone, reduced the risk of death, reinfarction and stroke by 15 to 34%; however, this benefit occurred at the expense of excess bleeding (odds ratio 1.80, 95% confidence interval 1.40 to 2.30) .
Very recently, three trials have been published suggesting that a shorter duration of dual antiplatelet therapy after stent implantation may be beneficial [19–21]. However, to date, it is unknown whether prolonged dual antiplatelet therapy will decrease major adverse cardiovascular and cerebrovascular events (MACCE) that occur more than 12 months after stent implantation, including very late stent thrombosis. Furthermore, it is uncertain what the optimal duration would be for long-term dual antiplatelet therapy. Therefore, given the lack of data from randomized studies, the aim of the OPTIDUAL study is to assess the benefits and safety of 12 versus 48 months of dual antiplatelet therapy in patients that receive a DES.