October 31st, 2013
Prolonged Dual Antiplatelet Therapy May Not be Necessary for Second-Generation Drug-Eluting Stents
The precise duration of dual antiplatelet therapy (DAPT) following implantation of a drug-eluting stent (DES) has been the subject of considerable controversy. On the one hand, prolonged therapy may help prevent late stent thrombosis, which was particularly evident in first generation DESs. On the other hand, the risk of stent thrombosis may have diminished in newer generation drug-eluting stents, and prolonged DAPT is associated with a greater risk for bleeding complications and additional expense and management issues.
In the Optimized Duration of Clopidogrel Therapy Following Treatment With the Zotarolimus-Eluting Stent in Real-World Clinical Practice (OPTIMIZE) trial 3119 patients with stable CAD or a history of low-risk acute ACS who received a zotarolimus-eluting stent (Endeavor, Medtronic) were randomized to either short-term (3 months) or long-term (12 months) DAPT. The results of OPTIMIZE were presented at TCT 2013 in San Francisco and published online in JAMA.
At one year there were no significant differences between the groups. The primary endpoint — the composite of death, MI, stroke, or major bleeding — occurred in 6% of patients in the short-term group versus 5.8% of patients in the long-term group (risk difference 0.17, CI, -1.52 – 1.86, p=0.002 for noninferiority). Between 3 months and 1 year there was an identical 2.6% rate of events in both groups.
The rate of major adverse cardiac events (MACE: the composite of death, MI, emergent CABG, or target lesion revascularization) at one year was 8.3% in the short-term group versus 7.4% in the long-term group (hazard ratio 1.12, CI 0.87-1.45). Between 3 months and 1 year, the MACE rate was 5.3% versus 4.3% (p=ns).
The stent thrombosis rate at one year was 0.8% in both groups. Between 3 months and 1 year there were 4 events (0.3%) in the short-term group versus 1 event (0.1%) in the long-term group (p=0.18).
At one year there were 10 (0.6%) major bleeds in the short-term group versus 14 (0.9%) in the long-term group (p=0.41). Between 3 months and 1 year there were 3 (0.2%) major bleeding events in the short-term group versus 6 (0.4%) in the long-term group (p=0.31).
The results were consistent across important subgroups, including patients with diabetes, low-risk ACS patients, and patients with multivessel disease or bifurcation lesions.
One important caveat mentioned by the authors is that the trial was designed based on a higher anticipated event rate, 9% instead of the actual 6% that occurred in the trial. It is possible, then, that small but significant differences may not have been detected.
The results, say the authors, are consistent with previous trials showing that prolonged DAPT may not be necessary with other second-generation DESs.
The authors write that “although not specifically studied,” the results “may be especially relevant for patients at high risk of bleeding complications following PCI, such as the elderly and patients with a history of hemorrhagic events.”
Click here to read — and answer — several important questions from CardioExchange Editors Rick Lange and David Hillis that were triggered by the OPTIMIZE findings.
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