JACC in a Flash: Time to Loosen the Reins on Antiplatelet Therapy after DES?

The first-generation drug-eluting stent (DES) was associated with remarkably reduced rates of in-stent restenosis and much less need for subsequent target lesion revascularization (TLR) compared to bare-metal stents (BMS). However, excessive inhibition of neointimal formation caused delayed vascular healing with incomplete endothelialization, which has been associated with an increased risk of late stent thrombosis (ST).

Because one of the strongest predictors for ST is early discontinuation of clopidogrel, prolonged dual antiplatelet therapy (DAPT) is highly recommended post-stenting. Current ACC/American Heart Association/Society for Cardiovascular Angiography and Interventions recommendations suggest, at a minimum, patients should be treated with clopidogrel 75 mg and aspirin 325 mg for 1 month after BMS implantation, 3 months after sirolimus-eluting stent (SES) implantation, 6 months after paclitaxel DES implantation, and, ideally, up to 12 months for patients not at high risk for bleeding.

Second-generation DES were developed to overcome safety concerns and maintain the efficacy similar to first-generation DES. Zotarolimus-eluting stents (ZES) have been associated with a higher rate of neointimal coverage at 8 months than SES on intravascular ultrasound (IVUS) and had a pattern of neointimal coverage similar to that of BMS on angioscopy.

Indeed, in an optical coherence tomography study by Jung-Sun Kim, MD, from Yonsei University College of Medicine in Seoul, and colleagues, most of the ZES struts (99.9%) were covered with neointima by 3 months, and late acquired malapposition was not seen. Therefore, a relatively short duration of DAPT may be an option in patients following ZES placement.

The feasibility of this approach was evaluated in a prospective multicenter registry by Hahn et al. Among patients who were event-free at 3 months (n = 812), clopidogrel was discontinued in 661 patients and was continued for longer than 3 months in 151 patients. Discontinuation of clopidogrel at 3 months did not increase the incidence of major adverse coronary events after adjustment for the propensity score.


In the October 9 issue of JACC, Hong et al. reported the results of RESET, which compared 3-month DAPT following Endeavor® ZES (E-ZES; Medtronic, Minneapolis, MN) implantation to standard therapy utilizing 12 months of DAPT following use of other DES. This prospective, open-label, randomized trial was conducted at 26 sites in Korea. One-year follow-up data were available for 98.5% of patients enrolled, including 1,059 patients in the E-ZES arm and 1,058 patients receiving another currently available DES plus standard DAPT.

The abbreviated 3-month DAPT regimen was noninferior to 12 months of standard therapy for the primary endpoint, which was a composite of cardiovascular death, MI, ST, target vessel revascularization (TVR), or bleeding at 1 year. The occurrence of ST was similar between the two groups. From 3 months through 12 months following the index procedure, there were no thrombosis events in the E-ZES group. Also, there were no significant differences for any of the other composite events or individual components of the primary endpoint.

The investigators noted that 1 year of clinical follow-up may not be sufficient to assess late outcomes (very late ST). Also, because very high-risk patients were not included, the results cannot be generalized to the entire population of patients undergoing stenting.

However, as an alternative PCI strategy, the RESET investigators said the implication is that 3 months of DAPT could be useful for selected patients following E-ZES placement, such as: those at risk for bleeding complications; those at risk of poor compliance with medication, especially the elderly population; those with a high probability of unexpected noncardiac surgery or invasive procedures; and those with a low risk of ST.

In an accompanying editorial, Bernhard Witzenbichler, MD, from Charité Hospital in Berlin, asked: has time has come to slacken the reins on antiplatelet therapy after DES? With newer-generation DES, he said, 6 months DAPT might be sufficient and 3 months not completely off-the-wall in low-risk groups. "However, the patient- and device-related criteria safely allowing early DAPT withdrawal or interruption still need to be determined. Until then, we should be cautious and do our best to avoid unplanned discontinuation of DAPT."


  1. Hahn JY, Song YB, Choi JH, et al. Circ J. 2010;74:2314-21.
  2. Kim BK, Hong MK, Shin DH, et al. J Am Coll Cardiol. 2012. doi:10.1016/j.jacc.2012.06.043
  3. Kim JS, Jang IK, Fan C, et al. JACC Cardiovasc Interv. 2009;2:1240-7.
    Witzenbichler B. J Am Coll Cardiol. 2012. doi:10.1016/j.jacc.2012.08.003.

Keywords: Neointima, Paclitaxel, Republic of Korea, Follow-Up Studies, Thrombosis, Drug-Eluting Stents, Tomography, Optical Coherence, Sirolimus, Stents

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