Antithrombosis in Patients with COVID-19 - Episode 8
Transcript: Gregory Piazza, MD, MS: If we do our very best and we can get these patients out of the ICU [intensive care unit], to the step-down unit, and eventually out of the hospital, our work doesn’t seem to be done. There seems to be a reasonable rate of patients suffering complications once they go home. Venous thromboembolism [VTE] seems to be front and center for that. Why is the risk of venous thromboembolism still elevated after patients are discharged from the hospital? Aren’t they better? Shouldn’t they be out of the woods?
Victor Tapson, MD, FCCP, FRCP: There are a couple reasons for that. One is this markedly reduced mobility we see. We see quarantined DVT [deep vein thromboembolism]. People come into the hospital without COVID-19 [coronavirus disease 2019] because they’re staying home and getting DVT just from stasis. If you put that together with COVID-19 and then you put someone through hospitalization—when you put someone in ICU, they’re losing days and days and days in terms of getting back on their feet.
What this points to is that we really should study and be aggressive with postdischarge prophylaxis. Look at EINSTEIN CHOICE and AMPLIFY-EXT. Look at MARINER and MAGELLAN. We’ve learned that low-dose DOAC [direct oral anticoagulant] prophylaxis is very safe. The bleed rate of a low-dose DOAC might be the same as aspirin. The risk-benefit analysis clearly favors doing this, or at the very least favors studying it.
With higher-risk patients, I’m going to assess them. If they have concomitant cancer or if they have marked reduced mobility, maybe I’ll look at D-dimer at discharge. These are the patients I want to put on prophylaxis, but I hope we can study this too.
Gregory Piazza, MD, MS: Absolutely. Alex, do we know what the rate is of VTE post discharge in patients with COVID-19? Or is it too soon to tell?
Alex Spyropoulos, MD, FACP, FCCP, FRCPC: That’s the other million-dollar question, isn’t it, Greg? What is the rate of VTE? One of the things we’ve done the last decade or so is have high-quality data to inform us on what a high-risk, medically ill patient looks like. We know that there’s a subset of these patients who are indeed at risk for developing severe VTE. Remember, in the medically ill population, when someone experiences a VTE event, it’s not the distal DVT that they get. It’s usually a central, major VTE, and an increased rate from the previous reports of VTE-related deaths. This is very different in terms of the first presentation of VTE and the surgical population, which tends to be younger and less comorbid and experience fewer cardiovascular morbidities. We know that the risk of VTE climbs dramatically in the first 3 weeks after hospital discharge and continues to about 6 weeks after discharge, and then afterward it plateaus. We’ve seen high-quality data from the MARINER trial. We’ve also seen high-quality data from the MAGELLAN and APEX trials. There are very consistent data.
Add COVID-19 on top of that, and in my view, a high VTE-risk population becomes a very high VTE-risk population, although we don’t have those data. We need those data desperately.
Something we’ve learned from key subanalyses is that we can also identify a low-bleed-risk population. If patients go through their hospitalization without a bleeding event, they are an excellent candidate for postdischarge prophylaxis. If they don’t have active cancer, if they don’t have bronchiectasis, if they’re not on dual antiplatelet therapies, if they don’t have other risk factors or a recent history of bleeding or active gastric duodenal disease, these all are appropriate patients.
Lastly, we just published a very important study with a lot of patients suggesting that certain key VTE risk factors—such as a history of VTE, a cancer history, history of thrombophilia, advanced age, and elevated D-dimer—are all very relevant in the COVID-19 population, either as separate risk factors or as part of a risk score, such as an IMPROVE [International Medical Prevention Registry on Venous Thromboembolism] score of 4 or more. These represent very high-risk patients who tend to have a 3-fold increased risk of VTE in the immediate postdischarge period and benefit from extended prophylaxis. In our institution, if you’re hospitalized with COVID-19 and you have an IMPROVE score of 4 or more or an elevated D-dimer or an advanced age, you’re getting postdischarge prophylaxis. Our regimen is what I call the MARINER regimen, which is 10 mg of rivaroxaban for up to about 4 to 6 weeks.
Gregory Piazza, MD, MS: That’s what I was going to ask you. That’s what you would do for your patients whom you feel are at high enough risk that they’re leaving the hospital and need something: 10 mg of rivaroxaban once daily.
Alex Spyropoulos, MD, FACP, FCCP, FRCPC: Yes. Of course, the minority of patients who are on certain antivirals that may interact with DOACs, and this is what Vic and you were saying earlier. There are some drug-drug interactions, so we have to be careful with the DOACs. Ritonavir or lopinavir, there are certain antivirals that would have some interactions that we’d have to be careful with. But the vast majority of patients can go home on a DOAC, as described.
Victor Tapson, MD, FCCP, FRCP: I thought I’d mention that we need more data on JAK inhibitors, IL-6 inhibitors, baricitinib, tocilizumab. What are these drugs doing with this inflammatory state? Are they helping us with the thrombotic state? There’s more to learn here. Maybe we’ll find out in big studies if patients who’ve received some of these drugs and reduced their cytokine storm are going to do better and have less thrombosis.
Gregory Piazza, MD, MS: Vic, along similar lines, we talked about getting patients out of the hospital. What about our patients, especially these elderly patients, who end up in an acute rehab setting or skilled nursing facility? Same approach? Do you give them a DOAC or a low-molecular weight heparin or something else for extended prophylaxis while they’re there?
Victor Tapson, MD, FCCP, FRCP: I strongly suggest a DOAC and a careful risk assessment. If they’re older, they’re already right up there in risk. As Alex said, do the best risk assessment you can, but when you’re older, you’re already high risk. Risk-benefit analysis almost always favors anticoagulation protection versus the risk of bleeding, but that’s got to be assessed. Bleed risk always has to be assessed.
Transcript Edited for Clarity