Several pivotal clinical trials have shown that, compared to a BMS, the DES is associated with significant reductions in the risk of restenosis and the need for target-lesion revascularization [
5,
6]. Early discontinuation of dual antiplatelet therapy has been identified as a risk factor for late stent thrombosis in patients with DES [
9]. Furthermore, it was suggested that some late clinical events that occur later than one year after DES implantation may be due to delayed arterial healing after the implantation of DES. Therefore, current guidelines recommend aspirin and clopidogrel at a dose of 75 mg daily for at least 12 months after DES implantation for patients that are not at high risk for bleeding. However, it remains unknown what the optimal duration might be for dual antiplatelet therapy and whether the risk-benefit ratio could be improved with long-term dual antiplatelet therapy for patients that receive DES. Due to the large number of DES implantations in the world each year, the optimization of dual antiplatelet therapy is important for both patient recovery and economic efficiency. The first randomized study on this issue was performed in Korea [
19]. They analyzed combined data from two multicenter trials, the REAL-LATE and the ZEST-LATE trials. That study found that no significant benefit was associated with continuing clopidogrel plus aspirin beyond the 12-month treatment following DES implantation. They saw no reductions in the incidence of myocardial infarction or death from cardiac causes. Moreover, the rates of composite outcomes (MI, stroke, death) were higher with clopidogrel plus aspirin than with aspirin alone, although the difference was not significant. Recently, two additional studies investigated the effects of long-term dual antiplatelet therapy. The EXCELLENT study, by Gwon
et al., showed that, at 12 months after DES implantation, patients treated with 12-month and 6-month dual antiplatelet therapy showed similar risks for target vessel failure, defined as the composite of cardiac death, MI and ischemia-driven target vessel revascularization [
20]. However, the non-inferiority margin was wide, and the study was underpowered for death and MI. In the other study, by Valgimigli
et al., 24 months of clopidogrel therapy in patients with DES or BMS was not significantly more effective than a 6-month clopidogrel regimen for reducing the composite endpoint of death, MI and cerebrovascular accident [
21]. In that study, two years of clopidogrel therapy resulted in a significant increase in bleeding episodes. Although those studies were interesting, and they suggested the possibility that a shorter dual antiplatelet therapy might be sufficient after DES implantation, they did not rule out the possibility that prolonging the clopidogrel plus aspirin treatment might result in a reduction of MACCE.
Given the importance of this subject, it is not surprising that a few clinical trials are currently ongoing to investigate optimal treatment times. The dual antiplatelet therapy (DAPT) study aims to compare the benefits and risks of 12 versus 30 months of dual antiplatelet therapy in patients undergoing PCI, and it has the largest number of subjects [
27]. Over 20,000 subjects will be enrolled at approximately 220 international clinical study sites. Most of the patients (>15,000) will receive a DES. Interestingly, in that prolonged combined antiplatelet therapy, patients will receive either clopidogrel or prasugrel, a new thienopyridine that recently appeared on the market. Another interesting ongoing trial aims to assess whether discontinuation of clopidogrel plus aspirin at six months after DES implantation would be non-inferior to a routine, one-year treatment [
28].