• Interventional Techniques & Devices Clinical Trials
• Coronary Artery Disease

Two years of dual antiplatelet therapy (DAPT) after drug-eluting stent (DES) implantation is no better than 6 months of DAPT in preventing adverse cardiac events, according to the Prolonging dual antiplatelet treatment after Grading Stent-Induced Intima Hyperplasia Study [PRODIGY; NCT000611286]. Marco Valgimigli, MD, PhD, University of Ferrara, Ferrara, Italy, reported the main results of the PRODIGY trial.

PRODIGY was an open-label, three-center, randomized, factorial assignment clinical trial to assess the efficacy and safety of prolonged DAPT (up to 2 years) with aspirin and clopidogrel after coronary stenting compared with currently recommended DAPT regimens (a minimum of 1 month after bare-metal stent [BMS] or 6 months after DES).

Inclusion criteria included males and females aged ≥18 years with coronary artery disease with low-, intermediate-, or high-risk coronary anatomy who were considered suitable for percutaneous coronary intervention with stent placement. The primary outcome was the composite endpoint of death, myocardial infarction (MI), or stroke, occurring from 31 days up to 24 months after intervention. The primary safety outcome was Bleeding Academic Research Consortium (BARC) type 2, 3, and 5 bleeding (Table 1) [Mehran R et al. Circulation 2011].

Patients (n=1970) who were scheduled for elective, urgent, or emergency coronary angioplasties were initially randomized in a 1:1:1:1 fashion to one of four stent types: everolimus-eluting stent, paclitaxel-eluting stent, zotarolimus-eluting stent, or third-generation thin-strut BMS. At 30 days, patients in each stent group were then further randomized to either 6 or 24 months of DAPT to ensure that the length of DAPT was equally distributed within each of the four stent groups.

Results showed that the cumulative risk of the primary outcome at 2 years was 10.1% with the 24-month treatment and 10.0% with the 6-month treatment (HR, 0.98; 95% CI, 0.74 to 1.29; p=0.91). The individual risks of death, MI, cerebrovascular accident, or stent thrombosis did not differ between the two groups.

Patients who received long-term DAPT had a roughly 2-fold greater risk of BARC (2, 3, or 5) bleeding events (HR, 2.17; 95% CI, 1.44 to 3.22; p=0.00018). The risks of TIMI-defined major bleeding (p=0.04) and red blood cell transfusion (p=0.04) were also increased in the 24-month clopidogrel group.

In patients who received first- or second-generation DES, outcomes failed to show a benefit of DAPT treatment for 24 months. According to Prof. Valgimigli, “While we cannot rule out the possibility that a smaller-than-previously anticipated benefit may exist, the clear increase in bleeding, transfusion, and net adverse clinical events suggests that current recommendations may have overemphasized the benefit over the risk of long-term treatment with aspirin and clopidogrel.”

These findings question the validity of current guideline recommendations, which were based on registry data. According to Prof. Valgimigli, if the risk of morbidity due to bleeding outweighs the anticipated benefit that is afforded by thienopyridine therapy, earlier discontinuation should be considered [Duke Heart Registry; JAMA 2007].

• © 2011 MD Conference Express