Teresa Carman, MD, details treatment and prevention options for vascular diseases induced by COVID.
Good afternoon this afternoon I'm going to talk about preventing and managing covid induced vascular disease. And I have brought no relevant disclosures early on in Covid, we realized that we were not quite sure what we were dealing with, particularly when we saw these patients with a profound waggle apathy and a number of different thrombosis complications. And these really left us a bit confused and a bit concerned about how we were going to optimally manage these patients. Most of the probiotic episodes we saw were debating thrombosis and pulmonary embolism but we also saw spanking thing thrombosis, cerebral thrombosis. We saw arterial promo embolism, myocardial infarction, stroke and acute limb ischemia. These are associated with a remarkable amount of morbidity and mortality. We started to realize that some of the severe complications we were seeing with covid were due to microvascular from moses. This was first identified on autopsy studies. We'll see traumatic episodes in the intra pulmonary charisma, in the kidneys, liver and then we dealt with other probiotic complications like our circuit plotting for ECMO and R. C. V. B. H. D. And then started to recognize the complicated complement mediated vascular injury. Covid vascular apathy um particularly in the outpatient setting. Well what we didn't know at the time and what we're still working through our some of the unknowns. We knew the thrombosis risk was high but we didn't know how to best mitigate that risk. We actually didn't know the magnitude of the problem because we didn't do systematic diagnostic studies in all of these patients. We knew that when patients presented with thrombosis, we needed to find the optimal treatment, but we have a myriad of drugs to do that. We didn't know what the best strategy would be and then what's the optimal strategy for prophylaxis. But we have numerous guidelines and we'll look at those but they're all quite very covid in and of itself is a complex condition and it affects all three of the angles of Burkle's try it, hyper probability stasis and and material injury. We have patient factors that were increasing our robotic risk. These patients are very sick. They have a lot of comorbidities, they're not moving around. We have viral factors and we recognized earlier that there was a lot of information and and emilio uh injury in these patients. But then we used to started to seem you mediate and complicated complement mediated from biotic episodes also. And then of course the human factors that we were dealing with within the blood. What we've come to recognize is that this Trumbo inflammatory process is a very complex process that involves both local as well as systemic interaction. We do have a lot of pro inflammatory cytokines and it's a very active inflammatory state. There's an ethereal inflammation and activation from the virus itself. There's a process that goes on called ketosis which is neutral film, extra cellular traps um which increase our calling. And then of course from moses that occurs at the level of the end of helium itself. Well, we've seen this before, but not to this magnitude. When we don't dealt with H one N one, we would see 20 to 50 year old patients come in typical influenza symptoms. Their rapid influenza testing was normal. They were not started on antivirals, they were presumed to have H one N one and they were sent home. But many of these folks would come back 3-5 days later with really significant arterial and venus normal anabolic of that. And we saw a very complicated patients in this setting. We saw increased nicu admissions, especially with BT and pregnancy, similar to what we're seeing now but nowhere near the same magnitude. And even at that time while we recognized it and while some centers did empirically start anti coagulation in this patient again, the magnitude was not at all this name. So what do we know about this uh process and venus on globalism? Well, this is a systematic review and meta analysis and different from many of the other meta analysis out there. This uh study reported on manuscripts that actually did full screening for DVT and pulmonary embolism. So it gives us an idea of the prevalence of the problem in these patients. So, in 17 studies that looked at reported prevalence of pulmonary embolism, Approximately 32% of patients pulmonary embolism, 32 studies that looked at the prevalence of deep vein thrombosis, 27%. It was clear from the meta analysis that DVT and Pe prevalence is higher with higher de diner levels and the odds ratio for mortality in these patients when they have covid. NBT versus covid alone was about 2.1. As I said, there was a number of different international, national and societal guidelines. All of these guidelines gave us recommendations for in hospital setting prophylaxis. But again, these were empirically. These were derived fairly early in the uh pandemic as well as giving us district post discharge recommendations. However, these guidelines really stem across the spectrum of options that we have all these patients. So no one guideline was necessarily consistent with the next. This pandemic spawned a number of anti coagulation trials. Many of these still ongoing. And this is just a representative of the trials that were available. Um You can see we have trials ongoing in the outpatient. Most of the trials did focus on these floor and ICU patients and very few on post discharge. So we still have some gaps in some unknowns in peace in this condition. What do we know? All patients need to be started on prophylaxis Unless they have an active probiotic event in which case we would obviously have to regulate them. Low molecular weight Heparin is preferred if they are admitted on a Dulac. We immediately changed them to low molecular weight Heparin or a fractionated Heparin if it's deemed necessary by their renal function. Di di mur body body mass or weight and waggle apathy. They affect our doses. We played very close attention to all of those parameters. And again we have national international and society guidelines but with that significant variability many centers have their own homegrown prophylaxis strategies. Now if we're faced with venus tomboy public event we have a lot of considerations in these individuals. First if there D timer is very high we like to confirm that they have a robotic, it obviously changes our management. We screen all of these patients for D. I. C. Covid quite philosophy and pharmacist opinion early on we saw a lot of this as we go through the variants. What we're starting to realize is each variant is a little bit different with respect to their problematic profile with respect to their E. Profiles and things like that. And then if they have a pulmonary embolism we do risk stratification and determine if there's a need for intervention carambola ISIS and these individuals or anti coagulation choice. Typically low and wait half an ARN fractionated heparin. We do realize that the heavens have some anti inflammatory properties and have been associated with improved outcomes. Wait based low molecular weight Heparin is preferred. Um It has less non specific anti inflammatory binding. Um And again if they're admitted on a doe actually change them to an alternative agent we use on fractionated happen particularly if there's renal insufficiency or end stage renal disease this requires more contact for monitoring and they require higher doses because of the inflammatory state. Um And if we have a patient with D. I. C. And the anti thrombin levels there's a concern for relative temperature resistance in the senate. We tend to avoid the dough X. Early on we had interactions with some of our anti retroviral retroviral rules that we were using. We also realize that many of these patients have anti cardio life and antibodies invaded two like protein antibodies and dogs should not be used in patients with A. P. L. A. We don't have enough data in this clinical setting to know what the A. P. L. A. Means. But we still avoid these drugs. There may be other clinical conditions or drugs that we use in this setting. That's also limit our to accuse at discharge. We typically try to avoid warfarin unless the patient is going to a nursing facility or an L. Tack or if they have any stage renal disease. We want to avoid that need for contact and travel for monitoring. We prefer low molecular weight heparin. If the renal function supports that. A doe act I think if it's not contraindicated there's no anti possible but antibodies they don't have any state renal disease. The renal function is okay and they're demonstrating recovery. That means D. Timer is trending down. There's no waggle apathy and the inflammation is resolving and there's no other contraindicated medication. Many of these patients if they're recovering can be treated for three months Typical for a situational DVT or pulmonary embolism. But with prolonged admission, immobility and prolonged recovery recovery, some of these patients do need extended therapy. Well, what do we know about our other patients are at risk arterial patients and patients with cardiovascular disease. This is a trial that looked at pre hospital use of anti platelet agents and survival. And you can see this is about 3500 patients, 90 health systems and all these patients were over the age of 50. They did a propensity matched score cohort. And what you can see is most of the reduction was in patients with pulmonary embolism. There was a reduction in overall in hospital mortality with an absolute reduction of about 2.6%. And there were not a lot of hemorrhagic complications. There was some excess taxes and an increased risk for blood transfusion. And the number needed to treat was relatively low. In this cohort. About 39 patients. Similar results were seen in a in a V. A. Uh study. So 1200 V. A. Facilities they did to propensity matched cohorts, a 14 day cohort and the 30 day cohort for mortality. And you can see in the propensity match cohort uh where they looked at 14 day mortality, there was about a 4% risk reduction and in the 30 day uh mortality cohort. About a 6% mortality risk reduction. So we know that pre hospital use of aspirin, decreased mortality in these patients. And there are ongoing trials looking at anti platelet agents in these patients. Well, what about statin use? This is a trial that looked at patients who were in the age, a COVID cardiovascular disease registry. About 10,000 patients. The vast majority had underlined cardiovascular disease or hypertension on admission and about 42% were on status prior to admission. And you can see the morbidity and mortality in this population was fairly high. Well, there was an overall about 40% mortality reduction in patients who were on status prior to hospital admission. In this meta analysis that looked at 100 and 47,000 patients uh to a little bit different cohorts. A cohort of trials that looked at uh adjusted odds ratio and the adjusted odds ratio, mortality of patients on status was 1000.67. And trials that looked at the hazard ratio, adjusted hazard ratio mortality was about .73. So, in patients who come into the hospital on status, we did see overall reductions in mortality. Now that did not pan out when we started patients on statins as a therapeutic model. So, it really is making sure these patients are on good cardiovascular risk hair before they come into the we did see an increase in stat prescribing food that pandemic. Um and this was a retrospective evaluation prescribing practices. 158 practitioners. About 20,000 patient encounters encounters. And you can see pre pandemic prescribing rate was about 3%, just a little over 3% that dropped off sharply um when in person visits dropped off. But you can see that the uh increase in statin prescriptions, particularly in patients who were being seen by telehealth visits. Um through the early part of the pandemic. Um the in person prescribing went back to about baseline at about 3%,, Diabetes is a very interesting um risk factor in these patients. So, in patients with COVID-19 infection, there's a number of underlying clinical conditions that can be associated with both new onset hyperglycemia in diabetes, as well as worsening of glycemic control. In addition, patients who don't have covid but have um underlying risk. We've also seen that they're at risk for a new onset hyperglycemia in diabetes, even without covid infection. Due to some of the lifestyle changes that we've all had to endure. Well, what do we know about preventing diabetes, diabetes doesn't seem to increase the risk for infection. It does, however, seem to increase the risk for adverse outcomes, including icu admission, mechanical ventilation and mortality, especially if there's preexisting poor control. And there does seem to be an increased risk for long covid symptoms. Um And again, like the previous diagram showed increased nuance of hyperglycemia, including complications like DK and HHS have been seen. We also realized that the lockdown had a lot of impact on our modifiable cardiovascular risk factors. So adults and adolescents in general for more sedentary days. That studies that looked at step counts and active days showed a decreased number of step count and fewer active days. There was an overall increase in alcohol consumption and many adults as well as students. College students reported weight gain. There was little to no effect on smoking or faculties which I guess is a good fallout from this. Between conclusion, COVID-19 demonstrates a clear effects on our vascular events. The majority of these events were being a strong symbolic. The cardiovascular events also increased given the risk of E. T. And the impact prophylaxis guidelines were implemented. These remain in place. There's a lot of ongoing investigation and modifications are to be expected Again, each of these ways seems to behave a little bit differently with respect to what we see in these patients. Given the impact of cardiovascular disease on outcomes, focusing on modifiable cardiovascular risk factors is really important. Making sure that all of our outpatients are on aggressive goal directed medical therapy for the underlying cardiovascular disease risk. This should be reviewed and implemented in all of our patients and with that I thank you for your attention