DENVER, CO — Dual-antiplatelet therapy (DAPT) after PCI in patients with acute coronary syndromes might sometimes be shortened to as little as 3 months using a polymer drug-eluting stent (DES) loaded with sirolimus and an endothelium-promoting antibody—that is, if a preliminary study’s results are confirmed in large randomized trials[1].
Observers of the Short-term Dual Antiplatelet Therapy in Patients With ACS Treated With the COMBO Dual-Therapy Stent (REDUCE) trial, presented here at TCT 2017, uniformly said it was too underpowered for firm conclusions, and some also raised questions about its mixed-bag composite primary end point.
Others took issue with the declaration of noninferiority for 3-month DAPT, which was compared with 12-month DAPT in the diverse ACS cohort, when some predefined secondary end points for shorter DAPT “went in the wrong direction” even if they fell short of significance.
The novel COMBO stent (OrbusNeich) used in REDUCE not only elutes restenosis-fighting sirolimus, it also administers an antibody agent that attracts endothelial progenitor cells. They promote reendothelialization at the PCI target site, which is supposed to reduce the risk of thrombosis.
The device is available in Europe, having gained the CE Mark in 2013 after safety and efficacy comparisons with the paclitaxel-eluting Taxus Liberté stent (Boston Scientific) in patients with symptomatic chronic CAD.
The safest and most effective DAPT duration after coronary stenting in patients with ACS is unknown; such patients are at increased risk of stent thrombosis compared with stable patients getting PCI. The treatment aims to achieve an acceptable balance between risk of bleeding with DAPT on board vs the risk of ischemic events if it is withdrawn.
The message from REDUCE is that the ultrashort 3-month DAPT duration is noninferior to a more conventional 12-month course of DAPT specifically in patients with ACS getting a DES, according to Dr Harry Suryapranata (Radboud University Medical Center, Nijmegen, the Netherlands), who presented the study.
The trial’s 1496 patients included about one-half with ST-segment-elevation MI (STEMI) and about half with either unstable angina or non-STEMI, he said.
At 12 months for the 751 patients randomized in hospital to the short DAPT course and the 745 randomized to the longer DAPT duration showed an 8.2% and 8.4% rate for the primary end point, respectively (odds ratio 0.97, 95% CI 0.67–1.41, P noninferiority <0.001).
The primary end point was a composite of all-cause mortality, MI, stent thrombosis, stroke, target-vessel revascularization (TVR), and Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding. Patients were entered over 2 years at 36 hospitals in Europe and Asia.
The results suggest that the short DAPT strategy could be considered for some patients getting the COMBO stent, “even in an ACS population,” Suryapranata said when presenting the trial here.
No Significant Differences in Secondary End Points in REDUCE
| Secondary end points | 3 mo DAPT, n=729 (%) | 12 mo DAPT, n=734 (%) | P |
|---|---|---|---|
| All-cause mortality | 1.9 | 0.8 | 0.07 |
| Cardiac mortality | 1.1 | 0.4 | 0.13 |
| MI | 2.3 | 1.9 | 0.57 |
| Stent thrombosis* | 1.2 | 0.4 | 0.08 |
| Target-lesion revascularization | 3.3 | 3.4 | 0.35 |
| Bleeding | 2.5 | 3.0 | 0.54 |
|
*Definite or probable |
|||
As a panelist following that presentation, Dr Eric Peterson (Duke University Medical Center, Durham, NC) said he takes issue with the implication that the COMBO may be appropriate for people who might especially benefit from shorter-duration DAPT, such as those at increased risk of bleeding.
“You’re not exactly testing that population here,” he said. The trial’s event rate suggests that its patients don’t well represent “the high-risk group that might be at risk and wanting a shorter duration” of DAPT.
“So while I would extend it to the very healthy, I’m not 100% sure that I’d extend it right yet to all comers,” Peterson said.
Also on the panel, Dr Deepak Bhatt (Brigham & Women’s Hospital, Boston, MA) took issue with the trial’s noninferiority claim. “I think it’s hard to claim that when mortality and, in this case, stent thrombosis are both going in the wrong direction,” he said.
“Yes, it’s not powered for that, but it’s hard to feel good about claiming noninferiority for this composite end point,” Bhatt said, “with the trends going the wrong way.”
Dr Robert Harrington (Stanford University, CA), also a panelist, brought up another issue with the secondary end point, which represents the components of the primary end point and combines ischemic events with bleeding events—those outcomes DAPT seeks to balance.
“You’ve put them together, and you’ve created a noninferiority comparison that is very difficult now to tease out, since you do have the excess of ischemic events, and the bleeding events are the same,” Harrington said.
The underpowered study is nonetheless “provocative,” Bhatt said. It’s appropriate to be seeking shorter DAPT regimens, and conducting trials to show they are safe and effective, “even in ACS.”
Suryapranata discloses receiving institutional research support for REDUCE from OrbusNeich. Peterson reports no relevant financial relationships. Bhatt discloses that he has received research funding from Amarin, Amgen, AstraZeneca, Bristol-Myers Squibb, Chiesi, Eisai, Ethicon, Forest Laboratories, Ironwood, Ischemix, Lilly, Medtronic, Pfizer, Roche, Sanofi, and the Medicines Company. Harrington discloses receiving grants or research contracts from AstraZeneca, the Medicines Company, Portola, St Jude Medical, Sanofi, Novartis, Bristol-Myers Squibb, and Jannsen; consulting or serving on speaker’s bureaus for Amgen, Gilead, Medscape, MyoKardia, the Medicines Company, and Bayer; and having equity interest in MyoKardia, Element Science, and Scanadu.
Follow Steve Stiles on Twitter: @SteveStiles2. For more from theheart.org | Medscape Cardiology, follow us on Twitter and Facebook.
Tidak ada komentar:
Posting Komentar