Final findings from the COBRA-REDUCE randomised trial assessing 14-day dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) with the Cobra PzF (CeloNova BioSciences) nanocoated stent have shown that the device did not meet its non-inferiority criteria with respect to thrombotic ischaemic events compared to standard drug-eluting stents with three to six months of DAPT.
This was the conclusion presented by Robert Byrne (RSCI University of Health Sciences, Dublin, Ireland) who detailed the COBRA-REDUCE trial findings during a late-breaking trial session at CRT 2022 (27 February–1 March, Washington DC, USA).
Further to the headline finding, Byrne detailed that at 12 months the trial’s composite ischaemic endpoint of all-cause death, myocardial infarction (MI), definite or probable stent thrombosis, ischaemia-driven target lesion revascularisation (TLR) or ischaemic stroke was significantly higher in patients treated with the Cobra PzF stent, primarily driven by an increased rate of ischaemia-driven TLR.
Byrne commented that while the results “do not support a routine strategy of Cobra PzF stenting with 14 days DAPT in patients receiving oral anticoagulants”, he said that the investigational device may benefit selected patients with high bleeding risk or those with whom an early interruption of DAPT for surgery, for example, is likely.
The COBRA-REDUCE study randomised 996 high-bleeding-risk patients across 59 enrolling global sites to receive either the Cobra PzF stent (n=495) with 14-day DAPT or a US Food and Drug (FDA)-approved drug-eluting stent (n=501) with three or six months DAPT. During his presentation, Byrne described Cobra PzF as a drug-free stent coated with a polyzene-F polymer, which is “thromboresistant, non-inflammatory and pro-healing”. The thin-strut stent has a thickness of 71μm and is made of cobalt-chromium alloy, he said.
Preclinical data for the device suggest thromboresistance and there is also a suggestion that healing and neointimal thickness is lower in comparison with a bare-metal stent, Byrne detailed in his presentation, adding that existing data from the PzF SHIELD trial, published in 2017, show “encouraging” clinical results, leading to the approval of the stent by the FDA in that same year.
The COBRA-REDUCE trial looked at the use of the device in high bleeding risk patients in particular. Investigators hypothesised that in patients undergoing PCI who were receiving oral anticoagulation, with or without dose reduction, a 14-day duration of DAPT after stenting with Cobra PzF, versus three to six months duration of DAPT after stenting with a standard FDA-approved drug-eluting stent would provide superior outcomes in terms of bleeding and non-inferior outcomes in the composite of death, MI, stent thrombosis and ischaemic stroke.
During his presentation, Byrne noted that, as is typical for patients with high bleeding risk, patients were typically older as compared to those normally seen in drug-eluting stent trials, with a mean age of around 74 years. Over a third of patients had diabetes, and comorbidities were “relatively well represented” in the patient population. All patients had at least one major criterion for high bleeding risk, and about 40% of patients had greater than two major criteria, according to the Academic Research Consortium for high bleeding risk (ARC-HBR) criteria.
Oral anticoagulation dose intensity could be reduced at the discretion of the treating physician, Byrne explained, noting that patients with dose reduction were seen more frequently than in patients who had drug-eluting stent implantation, which was associated with a longer duration of DAPT prescribed per protocol.
Detailing the results, Byrne explained that the primary endpoint, incidence of BARC level 2‒5 bleeding after 14 days was seen in 7.79% of patients with the Cobra PzF stent, compared to 9.75% with the standard strategy. “The difference of two percentage points was less than expected and not statistically significant,” he told CRT attendees.
Furthermore, the thrombotic co-primary endpoint of all-cause death, MI, stent thrombosis or ischaemic stroke was seen in 7.52% with the Cobra PzF strategy compared to 4.9% in the drug-eluting stent group. “Non-inferiority was not declared,” Byrne commented.
Secondary bleeding endpoints were statistically similar between the two groups, Byrne noted, and outlining the secondary thrombotic endpoints, he drew attention to the primary endpoint of interest, the composite thrombotic embolic endpoint, which occurred in 13.1% in the Cobra group and 8.7% in the standard drug-eluting stent group. “This was driven by a difference in ischaemia-driven target lesion revascularisation in favour of the drug-eluting stent”, said Byrne.
Noting some limitations of the study, Byrne acknowledged that it was an open-label design, and added that there was a difference in anticoagulation dose intensity reduction, which was at the discretion of the operator, “confounding somewhat the comparison of bleeding events between the groups”.
In his concluding remarks, Byrne told the CRT audience that in patients undergoing PCI for acute or chronic coronary syndromes who are receiving oral anticoagulation, stenting with Cobra PzF stents with 14 days DAPT did not reduce bleeding and did not meet non-inferiority criteria with respect to thrombotic ischaemic events compared to standard drug-eluting stents with three to six months of DAPT.
“At 12 months the rate of the composite ischaemic endpoint was significantly higher in patients treated with the Cobra PzF stent and that was a difference that was driven mainly by an increase in the rate of ischaemia-driven TLR,” Byrne said.