OPTIMIZE: 3-Month DAPT Safe with ZES
San Francisco, CA—Arctic-Interruption shows no added benefit, potential harm of prolonged DAPT
Results of two randomized studies presented Thursday at TCT 2013 provide further evidence that shorter-term dual antiplatelet therapy (DAPT) lasting 3 months may be safe with second-generation DES, and prolonged therapy beyond 1 year may be harmful.
For the trial, 3,119 patients with stable CAD or low-risk ACS undergoing PCI with a second-generation ZES were randomized to 3 months (n=1,563) or 12 months (n=1,556) of DAPT (100-200 mg aspirin and 75 mg clopidogrel daily).
At 1 year, there was no difference between 3-and 12-month DAPT in rates of the primary endpoint of NACCE (all-cause death, MI, stroke or major bleeding), meeting the criteria for noninferiority (see Figure).
After 3 months, ARC-defined definite or probable stent thrombosis rates were similar between the 3- and 12-month DAPT groups (0.3% vs. 0.1%; P=.18).
Feres concluded that, consistent with other recent studies, OPTIMIZE shows that second-generation DES may not always require 12 months of DAPT to reduce the risk of thrombotic events. The findings may be especially relevant for patients at high risk for bleeding following PCI, such as the elderly or those with a history of hemorrhagic events, he added.
Commenter Dean J. Kereiakes, MD, of The Christ Hospital Heart and Vascular Center in Cincinnati, Ohio, said the study design is flawed by inclusion of both efficacy and safety measures in a composite primary endpoint since the component event rates are discordant and lack power to detect clinically meaningful differences. However, several panel members questioned the clinical relevance of the criticism. Kereiakes observed that extrapolation from OPTIMIZE to current clinical practice may be difficult due to the trial’s exclusion of biomarker-positive ACS patients, and use of ZES only and a nonstandardized clopidogrel preload.
More bleeding with prolonged DAPT
Results of the ARCTIC-INTERRUPTION trial, presented by Gilles Montalescot, MD, PhD, of Centre Hospitalier Universitaire Pitié-Salpêtrière in Paris, found no benefit and greater risk of bleeding events when DAPT was continued beyond 12 months. The study was the second half of the randomized ARCTIC trial, which tested adjustment of antiplatelet therapy based on platelet function testing. At 1 year after stenting, roughly half of the original randomized cohort (n = 1,259), who were at lower risk than the overall population, were randomly assigned to either stop DAPT or continue it for up to 18 months.
At follow-up, there was no difference in the primary endpoint (composite of death, MI, ST or urgent revascularization) between patients who did or did not stop DAPT (4.3% vs. 3.8%; HR 1.17; 95% CI .68-2.03; P=.575). All ischemic endpoints, including death, were similar. However, those who discontinued DAPT experienced a lower rate of major or minor bleeding (0.5% vs. 1.9%; HR 0.26; 95% CI 0.07-0.91; P=.035).
But session panelist Paul A. Gurbel, MD, of Sinai Center for Thrombosis Research, Baltimore, said he was reluctant to draw any conclusions about DAPT duration from the study because it was underpowered to assess stent thrombosis. Moreover, he suggested future studies should include a measure of thrombotic risk.
OPTIMIZE was funded by Medtronic.
Feres reports receiving consultant fees/honoraria from Biosensors International, Eli Lily, Medtronic CardioVascular, Sanofi-Aventis and Terumo.
Gurbel reports receiving grants and consultant fees from several pharmaceutical manufacturers.
Kereiakes reports receiving consulting fees from Abbott Vascular, Ablative Solutions, Boston Scientific, HCRI, Medpace and REVA Medical.
Montalescot reports receiving research grants or consultant/lecture fees from several device and pharmaceutical manufacturers.