COBRA REDUCE Randomized Control Trial Results

Dr. Roxana Mehran: This was about close to a thousand patients enrolled over a four year period in 60 sites. And it took that long because what we wanted to do is to make sure that we would evaluate the COBRA Stent with a short duration, extremely short duration of only 14 days of DAPT versus a regular standard of care. And the idea was that we would end up with a lower incidence of bleeding without increasing thrombotic events comparing to a control group.

Dr. Aloke Finn: As you all know, patients on oral anticoagulation are extremely high risk for bleeding. That’s one of the important HBR criteria. And the question becomes what is the best strategy to treat these patients? So, the COBRA Reduce trial was an important trial that was released at TCT. And it really addressed that issue, how best to treat these patients.

Dr. Perwaiz Meraj: And as you can see in the trial results, this was really an ultra high-risk bleeding patient cohort. About 45% of the patients had two or more of the ARC-HBR criteria. All those patients were on oral anticoagulation and specifically, in the COBRA arm, you can see that there were about 68% of high-risk lesions. 20% of those were bifurcation lesions and a significant proportion of patients with diabetes.

Dr. Aloke Finn: The ischemic outcomes for the COBRA REDUCE arm in terms of the COBRA PzF Stent were extremely good overall. There were very few events, 0.6% rate of stent thrombosis with the discontinuation of DAPT at two weeks. I think this stent therefore is uniquely positioned, not only in the short-term to take short-term DAPT, because it heals much more quickly than drug-eluting stents, so there will be much more uncovered strut at early time points. But also late, where the quality of healing is simply superior to drug-eluting stents. So we may see a benefit, not only in terms of shortening DAPT, but also in terms of late events. And that’s probably where the one year or beyond data will become important.

Dr. Roxana Mehran: I was intrigued by the low event rates in both of these arms. And really importantly, I think in a certain patient population, for example, those patients who require urgent surgery or might need to go to surgery. That could be something that you might want to consider.

Dr. Aloke Finn: There are patients out there that are very high risk for bleeding, and 30 days of DAPT, in those patients, is probably unacceptable. So there remain a subpopulation of patients who should be treated with this strategy just simply because their bleeding risk is extremely high.

Dr. Roxana Mehran: I do believe that there is a role for a very short duration of DAPT with this particular stent technology in treating HBR patients, those extremely high risk patients needing surgery or with prior bleed, where we’re really, really concerned about shortening, even shortening less than 30 days.

Dr. Perwaiz Meraj: The COBRA NanoCoated Stent is probably the most unique stent that’s come out in the market in years. And it’s coated with Polyzene-F. Polyzene-F is a fluoropolymer that really allows it to adsorb albumin. And I think that the anti-inflammatory and antithrombotic effects of that adsorption of albumin really Renu Virmani and Aloke Finn have done a great job in demonstrating this in vitro. And you can show that the healing effects, the thrombosis, the lack of antithrombotic events on the stent really make it a very unique item in our armamentarium for treating patients that are high bleeding risk and potentially even having high ischemic risk or high thrombotic risk.

Dr. Aloke Finn: As you all know, it’s a cobalt chromium alloy backbone stent, thin strut, less than a hundred microns, but it also has the Polyzene-F coating. Now that Polyzene-F coating is a permanent polymeric coating made up fluorinated polymer. And as you’re all familiar with, fluorinated polymers have extremely beneficial thrombo-resistant properties.

Dr. Perwaiz Meraj: It’ll be very interesting to see what happens out to 12 months. We know that high bleeding risk patients don’t suddenly don’t become low risk bleeding patients after six months. So we can imagine that the bleeding outcomes will persist and continue. The question comes what happens after their DAPT duration is ceased in the DES arm as compared to the COBRA arm. And what happens to long-term therapy? The other part of the 12 month data that I’m personally very interested in is medication compliance. This is a very unique study. Most clinical trials are looking at a pure stent versus stent comparison. And that’s not what this study is really doing. It’s a therapy comparison. It’s a therapy comparison using the stent as part of that therapy. So what I mean by that is saying that in a high bleeding risk cohort, we’re not just looking at putting a stent in, and that stent is not going to reduce the bleeding, but it’s the way we treat the patient after that stent that may reduce the bleeding.