Meeting News CoveragePerspective

OUTSIDE START: Cilostazol may be safe bridging therapy for DAPT interruption

SAN DIEGO — Patients with a high–thrombosis-risk paclitaxel-eluting stent who were given cilostazol before undergoing a surgical procedure safely transitioned off dual antiplatelet therapy and had low rates of bleeding and major adverse cardiac events in the perisurgical period, according to data presented at the Society for Cardiovascular Angiography and Interventions Scientific Sessions.

Charles L. Laham, MD, FSCAI, and colleagues reported 8-year experience with outpatient cilostazol bridging in patients with paclitaxel-eluting stents who underwent surgery during the at-risk thrombosis period.

Charles Laham

Charles L. Laham

“Patients on [dual antiplatelet therapy] can be a challenge to manage with surgery because there are significant risks of [stent thrombosis] if DAPT is stopped, while there are also significant risks of bleeding if it is not stopped,” Laham, an interventional cardiologist at Holy Family Memorial Hospital in Manitowoc, Wisc., said. “To manage these ‘double jeopardy’ risks, we evaluated bridging antiplatelet therapy using the shorter-acting antiplatelet drug cilostazol.”

Cilostazol is a phosphodiesterase inhibitor-type 3 with a 12-hour half-life approved for use in claudication.

Laham said at a press conference that the decision to consider cilostazol for bridging therapy was “out of clinical necessity and not intended as research” and was thus a retrospective study.

All patients in the OUTSIDE START study stopped both DAPT agents 8 days before their surgical procedure. Seven days before surgery, the patients started receiving cilostazol 100 mg twice per day or 50 mg, if intolerant of the full dose, especially if undergoing high–bleeding-risk surgery.

Lower bleeding risk patients stopped cilostazol 24 to 30 hours prior to the procedure and resumed DAPT 12 to 24 hours after surgery. Patients at higher risk for bleeding during surgery stopped cilostazol 54 to 60 hours before surgery and resumed DAPT 24 to 36 hours after surgery. Patients were considered “fully bridged” if they received at least 600 mg of cilostazol prior to surgery and resumed DAPT by at least 48 hours after surgery, according to a press release.

Overall, 108 patients who had paclitaxel-eluting stents had 183 operations with a cilostazol bridge from 2005 to 2012, from half to 60 months after implantation.

Laham and colleagues assessed the incidence of MACE and bleeding during bridging and within 30 days after surgery.

According to results presented at SCAI 2015, 171 patients who were fully bridged at an optimal dose of greater than 500 mg experienced no MACE. The cilostazol success rate was 100% on treatment and 98% by intention to treat, Laham said.

Twelve patients in the study did not receive the full cilostazol bridge/DAPT resumption protocol due to surgeon or personal preference or other varying reasons; of those, four experienced MACE, according to the release, for an overall MACE rate of 2.2%. These four events included urgent repeat PCI at 7.5 months, death at 12.5 months, urgent repeat PCI at 28 months and MI at 40 months. The overall MACE rate was 2.2% in the study, with events exclusively in these four essentially unbridged patients, Laham told Cardiology Today. “These low MACE rates compare to historical MACE rates of 7% to 35% with DAPT interruption postoperatively with paclitaxel-eluting stents in the studied period,” he said.

The researchers also analyzed data from 55 patients who underwent surgery and stopped DAPT within the first year. In those patients with paclitaxel-eluting stents during the peak risk period, the 1-year MACE rate was 1.8% overall and 0% among those who were adequately bridged.

The researchers noted that the current study involved only patients who had received higher thrombotic risk paclitaxel-eluting stents, but did not include patients with newer-generation stents.

“This study is hypothesis-generating,” Laham said. “All these concepts ideally should be further verified, preferably in controlled trials involving the current generation of drug-eluting stents and bare-metal stents with all current antiplatelet agents in current use and respecting current DAPT duration guidelines.”

In addition, “close patient and surgeon involvement, regular discussion and postoperative follow-up appears essential to bridging success,” he said. “Alternative strategies may be in order for those in whom protocol noncompliance occurs, [such as] inpatient monitoring, alternative bridging, considering cancelling the procedure and/or insistence on urgent DAPT resumption,” among other considerations.

Reference:

Laham CL, et al. Late-Breaking Clinical Trials. Presented at: Society for Cardiovascular Angiography and Interventions Scientific Sessions; May 6-9, 2015; San Diego.

Disclosure: The researchers report no relevant financial disclosures.

SAN DIEGO — Patients with a high–thrombosis-risk paclitaxel-eluting stent who were given cilostazol before undergoing a surgical procedure safely transitioned off dual antiplatelet therapy and had low rates of bleeding and major adverse cardiac events in the perisurgical period, according to data presented at the Society for Cardiovascular Angiography and Interventions Scientific Sessions.

Charles L. Laham, MD, FSCAI, and colleagues reported 8-year experience with outpatient cilostazol bridging in patients with paclitaxel-eluting stents who underwent surgery during the at-risk thrombosis period.

Charles Laham

Charles L. Laham

“Patients on [dual antiplatelet therapy] can be a challenge to manage with surgery because there are significant risks of [stent thrombosis] if DAPT is stopped, while there are also significant risks of bleeding if it is not stopped,” Laham, an interventional cardiologist at Holy Family Memorial Hospital in Manitowoc, Wisc., said. “To manage these ‘double jeopardy’ risks, we evaluated bridging antiplatelet therapy using the shorter-acting antiplatelet drug cilostazol.”

Cilostazol is a phosphodiesterase inhibitor-type 3 with a 12-hour half-life approved for use in claudication.

Laham said at a press conference that the decision to consider cilostazol for bridging therapy was “out of clinical necessity and not intended as research” and was thus a retrospective study.

All patients in the OUTSIDE START study stopped both DAPT agents 8 days before their surgical procedure. Seven days before surgery, the patients started receiving cilostazol 100 mg twice per day or 50 mg, if intolerant of the full dose, especially if undergoing high–bleeding-risk surgery.

Lower bleeding risk patients stopped cilostazol 24 to 30 hours prior to the procedure and resumed DAPT 12 to 24 hours after surgery. Patients at higher risk for bleeding during surgery stopped cilostazol 54 to 60 hours before surgery and resumed DAPT 24 to 36 hours after surgery. Patients were considered “fully bridged” if they received at least 600 mg of cilostazol prior to surgery and resumed DAPT by at least 48 hours after surgery, according to a press release.

Overall, 108 patients who had paclitaxel-eluting stents had 183 operations with a cilostazol bridge from 2005 to 2012, from half to 60 months after implantation.

Laham and colleagues assessed the incidence of MACE and bleeding during bridging and within 30 days after surgery.

According to results presented at SCAI 2015, 171 patients who were fully bridged at an optimal dose of greater than 500 mg experienced no MACE. The cilostazol success rate was 100% on treatment and 98% by intention to treat, Laham said.

Twelve patients in the study did not receive the full cilostazol bridge/DAPT resumption protocol due to surgeon or personal preference or other varying reasons; of those, four experienced MACE, according to the release, for an overall MACE rate of 2.2%. These four events included urgent repeat PCI at 7.5 months, death at 12.5 months, urgent repeat PCI at 28 months and MI at 40 months. The overall MACE rate was 2.2% in the study, with events exclusively in these four essentially unbridged patients, Laham told Cardiology Today. “These low MACE rates compare to historical MACE rates of 7% to 35% with DAPT interruption postoperatively with paclitaxel-eluting stents in the studied period,” he said.

The researchers also analyzed data from 55 patients who underwent surgery and stopped DAPT within the first year. In those patients with paclitaxel-eluting stents during the peak risk period, the 1-year MACE rate was 1.8% overall and 0% among those who were adequately bridged.

The researchers noted that the current study involved only patients who had received higher thrombotic risk paclitaxel-eluting stents, but did not include patients with newer-generation stents.

“This study is hypothesis-generating,” Laham said. “All these concepts ideally should be further verified, preferably in controlled trials involving the current generation of drug-eluting stents and bare-metal stents with all current antiplatelet agents in current use and respecting current DAPT duration guidelines.”

In addition, “close patient and surgeon involvement, regular discussion and postoperative follow-up appears essential to bridging success,” he said. “Alternative strategies may be in order for those in whom protocol noncompliance occurs, [such as] inpatient monitoring, alternative bridging, considering cancelling the procedure and/or insistence on urgent DAPT resumption,” among other considerations.

Reference:

Laham CL, et al. Late-Breaking Clinical Trials. Presented at: Society for Cardiovascular Angiography and Interventions Scientific Sessions; May 6-9, 2015; San Diego.

Disclosure: The researchers report no relevant financial disclosures.

    Perspective
    Michael R. Jaff

    Michael R. Jaff

    This is an interesting observational study about cilostazol and its potential role in patients with ACS and CAD. It is particularly interesting to me given that cilostazol has an on-label indication for treatment of mild to moderate intermittent claudication due to peripheral artery disease in the limbs. We don’t often have a chance to take what we have in PAD and share that with the cardiac community; it is usually the other way around and we extrapolate cardiac data for our treatment of patients with PAD. [This study provides] a novel little twist in the armamentarium of therapies that now is going to be studied.

    • Michael R. Jaff, DO
    • Cardiology Today Editorial Board member Massachusetts General Hospital VasCore Training and Education Center

    Disclosures: Jaff reports serving as a noncompensated advisor for Abbott Vascular, Boston Scientific, Cordis and Medtronic; serving as a compensated advisor for Cardinal Health; equity investment in PQ Bypass; and serving on the board of VIVA Physicians Inc. and CBSET.

    Perspective
    Roxana Mehran

    Roxana Mehran

    This is the first major report of large numbers of patients [using this strategy]. It is very interesting. Obviously, it is hard to randomize patients [to this strategy]. The number of patients is small. The event rate is zero. I never believe a zero event rate for anything. If we [study] more patients, I think we will see more events.

    This [study addresses] a very important questions that clinicians have all the time: [What to do when] a stent is placed and the patient needs urgent surgery during the time when DAPT is still mandatory for protection against stent thrombosis? We do need an answer to this question. Use of cilostazol is an interesting, novel way of bridging patients. Let’s see if it can be repeated [in further studies].

    • Roxana Mehran, MD
    • Cardiology Today’s Intervention Associate Medical Editor Icahn School of Medicine at Mount Sinai

    Disclosures: Mehran reports financial ties with Abbott Laboratories, AstraZeneca, Boston Scientific, Bristol-Myers Squibb, CSL Behring, Covidien, Janssen Pharmaceuticals, Maya Medical, Merck, Sanofi Aventis and The Medicines Company.

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