Another trial of extended clopidogrel has done little to settle the confusion about how long dual antiplatelet therapy should be continued following drug-eluting–stent (DES) placement, with one commentator saying the studies available on this topic were like “the blind leading the deaf.”
The OPTIDUAL trial, presented at the European Society of Cardiology 2015 Congress, showed no significant difference in the primary end point—a composite of all-cause death, MI, stroke, and major bleeding—between patients taking 12 months of clopidogrel and those continuing on the drug for 4 years. However, a post hoc analysis showed there was a strong trend toward fewer ischemic events in the long-term group and no sign of an increased major bleeding risk. All patients were taking long-term aspirin and were judged to be at low bleeding risk.
Lead investigator Dr Gérard Helft (Hôpital Pitié-Salpétrière, Paris, France) said the OPTIDUAL results supported those from the larger Dual Antiplatelet Therapy (DAPT) trial presented last year, which showed a reduction in ischemic events with extended dual antiplatelet therapy but an increased risk of bleeding.
According to Dr. Helft, the results are consistent with DAPT trial showing the value of prolonging DAPT after the drug-eluting–stent placement. But putting all the data together, it is still a difficult question. If patients are at a low bleeding risk at 1 year, we can consider extended DAPT, because you may reduce thrombotic risks, but bleeding risk has to be a key consideration.
He noted that the stents used were a mixture of first and second generation. “More than half the patents in this study received second-generation drug-eluting stents. I don’t think the message from our study will be changed even for patients given third-generation stents because the rate of stent thrombosis in this study was very low—about 0.3% to 0.4%.”
The OPTIDUAL study randomized 1385 patients who had undergone drug-eluting stenting and who had received dual antiplatelet therapy (clopidogrel and aspirin) for 1 year to continue on dual therapy for an additional 36 months or to just continue on aspirin alone.
Results showed no statistical difference between the groups for the primary end point, which include both efficacy and safety components.
OPTIDUAL Major Results
|End point||4 years dual therapy, n=695 (%)||1 year dual therapy, n=690 (%)||P|
|Death/MI/stroke/major bleed (primary end point)||5.8||7.5||0.17|
|Death /MI/stroke (post hoc analysis)||4.2||6.4||0.06|
Better Patient Stratification Needed
Designated discussant of the OPTIDUAL trial, Dr Lars Wallentin (Uppsala Hospital, Sweden), pointed out that a recent meta-analysis of all data on 1 year vs more than 1 year dual antiplatelet therapy shows that while MI and stent thrombosis are reduced with extended therapy, bleeding is increased and there appears to be an increase in noncardiovascular mortality.
“So while the OPTIDUAL results do support the DAPT trial in that they suggest a reduction in ischemic events, these results do not address safety, bleeding, and mortality,” he said. Noting that the ischemic event rates were very low in OPTIDUAL (annual death/MI/stroke rate of 0.9%), he added: “These patients are very low risk so there is not a great need for extended antiplatelet therapy in this population.”
Wallentin called for better risk stratification “so we can select the best population who will benefit most from extended DAPT.” As there are no validated tools for this, he said these need to be developed based on clinical criteria, imaging data showing the extent of coronary artery disease, and biomarker data on cardiac, renal, and inflammatory markers.
Helft G et al. The OPTIDUAL trial: 12 vs 48 months of clopidogrel after drug-eluting stent placement, European Society of Cardiology 2015 Congress; August 31, 2015; London, UK. Abstract 3159.