Dual antiplatelet therapy (DAPT) with a P2Y₁₂ inhibitor plus aspirin decreases drug-eluting stent (DES) thrombosis [Mauri L et al. N Engl J Med. 2014]. Each year, approximately 5% to 10% of patients with a DES must interrupt DAPT to reduce perioperative bleeding. Premature discontinuation of DAPT, especially during the first postoperative year, results in stent thrombosis rates of 10% to 35%, inversely related to duration after stent placement [Moussa ID, Colombo A. Catheter Cardiovasc Interv. 2009; van Kuijk JP et al. Am J Cardiol. 2009]. The highest stent thrombosis rates have been observed in patients with a paclitaxel-eluting stent (PES) during DAPT discontinuation, leading to increased major adverse cardiac events (MACEs) for prolonged durations, up to 30 months poststenting [Garratt KN et al. Circulation. 2015].

Currently, there is no consensus on the best bridging strategy for patients with a DES discontinuing DAPT preoperatively [Kern MJ et al. Catheter Cardiovasc Interv. 2014]. DES bridging has been attempted with aspirin, heparin, glycoprotein IIb/IIIa inhibitors, low molecular weight heparins, and intravenous cangrelor, but success has been limited. Cilostazol, a phosphodiesterase inhibitor–type 3 that reversibly inhibits platelet activation and aggregation has shown promise as a third antiplatelet agent for high-risk patients and, given its shorter half-life, may be a consideration for perioperative bridging.

The OUTSIDE START Cilostazol Bridge Study, presented by Charles L. Laham, MD, Holy Family Memorial Hospital, Manitowoc, Wisconsin, USA, was a retrospective analysis conducted in patients who required surgery during the first 6 to 12 months after PES placement and discontinued DAPT. The analysis included consecutive patients who were bridged with cilostazol from 2 weeks to 60 months after a PES placement over an 8-year period.

The patients stopped DAPT 8 days before surgery and started cilostazol 100 mg BID on the seventh day preoperatively. Two dosing regimens of cilostazol 1300 mg were used to reduce the risk and degree of perioperative bleeding. Patients undergoing surgery with a low to moderate risk of bleeding had a goal of cilostazol 1300 mg, which they discontinued 24 to 30 hours before surgery. DAPT was resumed 12 to 24 hours after surgery. The goal for patients undergoing high-bleeding-risk surgery was cilostazol 1000 mg, which they stopped 54 to 60 hours prior to surgery. They restarted DAPT 24 to 36 hours after surgery. The primary end points were perioperative bleeding and MACE (cardiac death, myocardial infarction, or urgent revascularization) within the bridged period and up to 1 month after surgery.

A total of 108 patients with ≥ 1 PES who underwent 183 consecutive surgeries stopped DAPT and were bridged by cilostazol (Table 1). Of these, 104 (57%) surgeries were bridged with cilostazol 1300 mg, 60 (32%) with cilostazol 1000 mg, and 10 (5.5%) with 650 to 900 mg. A total of 171 surgeries were adequately bridged with > 600 mg of cilostazol. The remaining 12 patients received an inadequate preoperative dose of 0 to 600 mg cilostazol and failed to resume DAPT postoperatively. No MACE occurred among patients who were successfully bridged with cilostazol. Among patients who were not adequately bridged perioperatively, 1 MACE occurred in the first year, and of note, 3 occurred beyond 12 months, of which 1 occurred up to 40 months post-PES stent placement. The study results are shown in Table 1.

Perioperative cilostazol for DES bridging is feasible in patients at the highest risk of stent thrombosis with PES and completely off DAPT. No MACE or bleeding other than minor nuisance bleeding was reported in patients who were successfully bridged with cilostazol. Dr Laham concluded that this was a clinically driven hypothesis-generating feasibility study. The results should be verified in controlled trials using current-generation DES and bare metal stents with antiplatelet agents in current use.