As treatment for high-bleeding-risk (HBR) patients with acute or chronic coronary syndromes, the Cobra PzF nanocoated coronary stent followed by 2 weeks of dual antiplatelet therapy (DAPT) did not reduce bleeding and failed to demonstrate noninferiority to standard drug-eluting stents (DES) with 3 to 6 months of DAPT with respect to thrombotic events, according to study results presented Saturday at the TCT Connect virtual conference.
Robert A. Byrne, MB, BCh, PhD, of Mater Private Hospital, RCSI University of Medicine and Health Sciences, Dublin, presented the results of COBRA-REDUCE. The study was a randomized, open-label, active-controlled, assessor-blinded, multicenter trial that aimed to determine whether the Cobra PzF stent with a shorter-duration DAPT (14 days) results in a lower incidence of bleeding without increasing thrombotic events in comparison with U.S. Food and Drug Administration-approved second-generation DES with standard DAPT (3 to 6 months) in patients taking oral anticoagulants.
The Cobra PzF NCS (Celonova Biosciences) is made of a cobalt chromium alloy that is 71 micrometers thick. It is coated with polyzene-F, which is no more than 0.05 micrometers thick.
A total of 996 patients were enrolled between February 2016 and May 2020 in 59 sites in Europe and the U.S. Of those patients, who were deemed HBR because of a requirement for oral anticoagulants (vitamin K antagonist or non-vitamin K antagonist), 495 were randomized to the Cobra (treatment) group and 501 to the control (standard DES and DAPT).
The patients’ mean age was 74.4 years, 27% were women, 36.2% had diabetes, 12.1% had a history of stroke, and 6.6% had severe renal insufficiency; 29.3% of patients presented with acute coronary syndrome.
One co-primary endpoint was Bleeding Academic Research Consortium (BARC) 2-5 bleeding after 14 days. The two groups showed no difference in this outcome (treatment 7.5% vs. control 8.9%;p=0.477).
The other co-primary endpoint was a thrombotic composite of death, myocardial infarction (MI), stent thrombosis or ischemic stroke at 6 months. The Cobra stent failed to meet noninferiority (treatment 7.7% vs. control 5.2%; difference +2.5%; upper bound of 95% confidence interval, 5.15%; prespecified noninferiority margin difference range, 0% to 5%; p-noninferiority = 0.061).
Turning to secondary bleeding endpoints, there was no significant difference between the groups on BARC 3-5 bleeding after 14 days, BARC 3-5 bleeding after randomization or BARC 2-5 bleeding after randomization; however, BARC 1-5 bleeding after randomization was significantly lower in the Cobra group (13% vs. 18.3%; p=0.026).
A similar pattern was seen with secondary thrombo-embolic endpoints at 6 months. There were no significant differences between the groups on death, cardiac death, MI, definite or probable stent thrombosis or ischemic stroke; however, the Cobra group did have a significantly higher rate of ischemia-driven target lesion revascularization (3.7% vs. 0.9%; p=0.004).
Byrne concluded that despite failing to reduce bleeding and failing to show noninferiority with regard to thrombotic events, the Cobra stent was safe, with stent thrombosis rates “considerably lower than those seen in earlier trials” with high-bleeding-risk patients, despite only 14 days of DAPT. He added that ongoing follow-up and planned analysis of the secondary outcomes at 12 months is anticipated to assess comparative efficacy of the treatment arms in relation to the study devices.
During a press conference announcing the results, Byrne noted that the end of the study period coincided with the onset and early peak of the COVID-19 pandemic, which made it difficult to complete follow-up in a small number of patients.
The study received funding from Celonova Biosciences.