Coupling the Cobra PzF stent with just 14 days of dual-antiplatelet therapy (DAPT) fell short of expectations on two counts when pitted against contemporary drug-eluting stents (DES) and standard DAPT in high-bleeding risk patients in the COBRA-REDUCE trial.
"This is a negative trial but the performance of the study stent was actually quite good considering a short duration of DAPT," coprincipal investigator Robert A. Byrne, MB BCh, PhD, Cardiovascular Research Institute Dublin, Mater Private Hospital, Ireland, said at TCT Connect, the virtual meeting of Transcatheter Cardiovascular Therapeutics (TCT) 2020.
Cobra PzF (CeloNova Biosciences) is a thin 71 μm-strut cobalt-chromium stent nanocoated with a polyzene-F polymer that has been shown to improve thromboresistance and reduce inflammation and neointimal hyperplasia compared with bare metal stents in preclinical studies, he observed.
It was approved in the United States in 2017 for patients with symptomatic de novo coronary lesions based on results of the PzF Shield trial.
The open-label COBRA-REDUCE trial, conducted at 59 sites in the United States and Europe, enrolled 996 patients with acute or chronic coronary syndrome who met at least one Academic Research Consortium for High Bleeding Risk (ARC HBR) criterion and were receiving or had an indication for long-term oral anticoagulation (OAC) with a Coumadin-derivative or a novel OAC.
Byrne and colleagues hypothesized that 14 days of DAPT after stenting with the Cobra PzF would be superior in terms of BARC 2-5 bleeding and noninferior in the composite of death, myocardial infarction, stent thrombosis, or ischemic stroke to 3 to 6 months of DAPT after stenting with an FDA-approved second-generation DES.
In all, 481 patients were treated with the Cobra PzF stent and 499 patients with DES including Xience (Abbott) or Promus (Boston Scientific) in 53%, Synergy (Boston Scientific) in 24%, and Resolute Onyx (Medtronic) in 19%.
About 90% of patients had atrial fibrillation as the indication for long-term OAC, which consisted largely of apixaban, vitamin K antagonists, and rivaroxaban. Aspirin was used throughout the study in both groups.
OAC dose reductions were allowed at the investigator's discretion and were more common with DES than the Cobra PzF (56% vs 46%; P = .006), Byrne said.
At 6 months, BARC 2-5 type bleeding after 14 days or hospital discharge had occurred in 7.5% of patients treated with Cobra PzF and short DAPT and 8.9% of patients treated with DES and standard DAPT (P = .477).
The coprimary thrombotic composite endpoint occurred in 7.7% and 5.2%, respectively, which did not meet the noninferiority margin (P = .061; 95% upper limit CI, 5.15%).
Secondary bleeding and thromboembolic endpoints were not significantly different, except for ischemia-driven target lesion revascularization, at 3.7% in the Cobra group and 0.9% in the DES group (P = .004).
This compares favorably with that seen in other studies of high-bleeding risk patients with DES, Byrne said. In addition, definite/probable stent thrombosis was only 0.6% in both groups.
"This was a courageous, well-designed trial. Okay, it didn't make it but, without any drug, it was very ambitious," session comoderator Marie-Claude Morice, MD, Hôpital privé Jacques Cartier, Massy, France, said.
"I'm also much impressed by the very low rate of stent thrombosis, 0.6%," she added. "In the LEADERS FREE trial, the rate at 1 year was 2%, so it seems we are making progress even in the high-risk patient."
Panelist Pieter C. Smits, MD, PhD, Maasstad Hospital, Rotterdam, the Netherlands, said it's an important trial in an understudied patient population in terms of optimal DAPT, but questioned whether the investigators had any second thoughts about its design.
"I wonder if you would redesign your trial because you have done a trial, in which you have tried to establish a pharma strategy, and combined it again with a stent comparison," he said. "This dual-trial design makes the results less prominent on what we can do."
Smits also asked whether allowing investigators to limit the novel OAC dose may have negatively influenced the outcome. "I presume that investigators who will prescribe triple therapy for 3 to 6 months are more likely to reduce the NOAC dose compared to patients who only received 14 days of DAPT."
Byrne replied: "We certainly wanted to keep the trial as close to clinical practice as we could and, in our experience, many investigators do reduce the intensity of the OAC during the period of triple therapy, even though really the guidelines don't give this recommendation, although they have changed somewhat since we designed and started the trial."
Further analyses are planned into the OAC imbalance between the two groups, medication compliance, and discontinuation noncompliance, Byrne said. Follow-up and analyses of secondary outcomes at 12 months are also planned. As for the trial design, "we designed it specifically as a strategy trial; of course, you could make an argument for a factorial design," he said.
The study was sponsored by CeloNova BioSciences. Byrne reported an institutional research contract with CeloNova with a prior employer.
Transcatheter Cardiovascular Therapeutics 2020. Presented October 17, 2020.
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Cite this: 14-Day DAPT, COBRA PzF Stent Strike Out in COBRA-REDUCE - Medscape - Oct 19, 2020.