People on oral anticoagulation (OAC) undergoing percutaneous coronary intervention (PCI) did not fare well with a treatment tailored to their high bleeding risk — Cobra PzF stent implantation and a short duration of dual antiplatelet therapy (DAPT) — the COBRA-REDUCE trial showed.
At 6 months, the rate of actionable bleeds was similar between those randomized to Cobra PzF stenting with 14 days of DAPT and peers who had second-generation drug-eluting stent (DES) placement followed by the standard 3-6 months of DAPT (BARC 2-5 bleeding 7.5% vs 8.9%, P=0.477).
The lack of a significant reduction in bleeding was “somewhat surprising,” as the hypothesis of the study had been that the Cobra PzF group would have a superior outcome, according to Robert Byrne, MB BCh, PhD, of Mater Private Hospital, RCSI University in Dublin, in a presentation at the virtual TCT Connect conference.
The Cobra PzF and short DAPT strategy also failed to meet non-inferiority in terms of thrombotic events (combined incidence of death, myocardial infarction (MI), stent thrombosis, and ischemic stroke) at 7.7% versus 5.2% of controls (P=0.061 for non-inferiority).
No between-group differences were found in the individual endpoints of all cause death, cardiac death, MI, stent thrombosis, or ischemic stroke. Only excess ischemia-driven target lesion revascularization (TLR) was suggested for the Cobra PzF strategy (3.7% vs 0.9%, P=0.004).
Byrne highlighted the low event rates in both groups — especially the 0.6% incidence of stent thrombosis in both study arms — and the “very good performance” of second-generation DES in particular in the trial.
“I was surprised with these results. We will need to see these data more closely,” commented Roxana Mehran, MD, of Mount Sinai School of Medicine in New York City.
She said she is “still wondering” about the MI rates (2.8% for Cobra vs 1.7% for controls, P=0.279) and noted that TLR may be expected to be higher in a non-DES platform in an unblinded trial.
Cobra PzF is a thin-strut cobalt chromium stent with Polyzene-F nanocoating, instead of drug elution technology, for rapid healing. It was FDA approved in 2017 for PCI followed by 30 days of DAPT.
Short DAPT has been shown to help patients at high bleeding risk undergoing stenting with various devices.
The COBRA-REDUCE open-label trial was conducted at 59 sites in Europe and the U.S.
Investigators randomized 996 patients on long-term OAC at the time of PCI. The cohort averaged just over age 74, and women accounted for 28% of the group. Approximately 30% of patients had presented with an acute coronary syndrome.
Warfarin, apixaban (Eliquis), and rivaroxaban (Xarelto) were among the most popular OAC agents used by study participants. The most common indication for OAC was atrial fibrillation, which was noted in roughly 90% of patients. Few had mechanical heart valves or venous thromboembolism.
Patients in the control arm received second-generation FDA-approved DES (most commonly everolimus-eluting stents such as Xience).
People stayed on triple therapy until clopidogrel (Plavix) was withdrawn (at 14 days in Cobra group vs at 3-6 months with DES). Patients remained on aspirin and OAC, with OAC dose reduction permitted at the discretion of their site investigator.
Importantly, the DES plus standard DAPT group had significantly more patients undergo dose reduction of OAC within 6 months (56% vs 46% for Cobra group, P=0.006).
Moreover, the lack of bleeding benefit in the Cobra arm is likely “due to the anticoagulant being the primary reason for bleeding, rather than clopidogrel,” according to Cindy Grines, MD, president of Society for Cardiovascular Angiography and Interventions and of Northside Cardiovascular Institute in Atlanta.
She noted prior studies finding minimal or no advantage in bleeding reduction from stopping DAPT early, though these did not include patients on triple therapy.
Byrne noted that the tail end of COBRA-REDUCE trial enrollment coincided with the beginning of the COVID-19 pandemic. As such, follow-up remains incomplete in some patients and data on medication compliance not available to be shared, he cautioned.
“Ongoing follow-up and planned analysis of secondary outcomes at 12 months is awaited in order to assess comparative efficacy of the treatment arms in relation to the study devices,” he said.
“Integrated analyses of bleeding events according to medication compliance, OAC dose and number of ARC-HBR criteria will permit examination of interaction between treatment effect, anticoagulation intensity and baseline bleeding risk,” he added.
The trial was sponsored by CeloNova Biosciences.
Byrne disclosed a relevant relationship (institutional) with CeloNova Biosciences.