Interventionalists, Including PERTs, Grapple With VTE Risks of COVID-19

Randomized trials testing various anticoagulant strategies are coming, including the large US National Institutes of Health-sponsored ACTIV-4 trial, but given the recent spikes and surges in COVID-19 case numbers, many frontline doctors are still grappling with the thromboembolic risks associated with the infectious disease.

That was the consensus among a group of experts gathered to kick off the TCT Connect 2020. In a session dedicated to interventional cardiology in the COVID-19 era, Sanjum Sethi, MD (NewYork-Presbyterian/Columbia University Irving Medical Center, New York, NY), highlighted the struggle many physicians face when dealing with these critically ill patients at high risk for venous thromboembolism (VTE).

“Prior to the coronavirus, we had a pretty routine way of dealing with this,” said Sethi. “We would confirm the diagnosis of [pulmonary embolism (PE)] on the CT scan, and then risk-stratify the patient using both clinical and imaging markers, and then decide on the appropriate treatment strategy. Now with the advent of the coronavirus, a lot of this changed because a lot of the risk-stratification paradigms we normally have—things like clinical risk factors, imaging, and biomarkers—may actually be abnormal for other reasons if a patient has a severe COVID-19 infection.”

As the director of his center’s pulmonary embolism response team (PERT), Sethi said they had three times as many activations in March and April as they did during the same time frame in 2019. Given how strapped resources were at the height of the pandemic and also because of how sick some of the patients were, they performed fewer invasive procedures and prescribed more systemic thrombolysis with tPA. Additionally, more hemodynamic support than usual was also needed.

Sethi said the management of VTE is similar in patients with and without COVID-19, with unfractionated or low-molecular-weight heparin generally preferred, but that there are many unknowns when it comes to prevention.

“The question really is what to do about thromboprophylaxis?” said Sethi. “What do you about these patients that don’t have confirmed VTE and should we be giving more thromboprophylaxis than normal? And what should we be giving? Low dose? Weight-based? Intermediate dose? Full dose? Or treat based on D-dimer?”

During the presentation, Sethi highlighted several observational studies published to date, including a French study of 107 patients admitted to ICUs with COVID-19. Among these patients, 20.6% had a diagnosis of PE a median of 6 days after admission, most of whom were taking guideline-directed prophylaxis at the time of diagnosis. In a Dutch series, the cumulative incidence of any thrombotic event in critically ill ICU patients with COVID-19 was 31%, said Sethi. And yet in other studies, including one from Northern Italy, there was no evidence of symptomatic deep vein thrombosis in 388 patients with COVID-19 admitted to non-ICU hospital wards.

For Renu Virmani, MD (CVPath Institute, Gaithersburg, MD), important questions remain unanswered as to why pulmonary thromboembolism is increased with this viral infection. “The question really is if it’s in situ or if it’s coming from the right ventricle? What we have seen is that there is both an embolic phenomenon—you see a thrombus in the right ventricle, and a lot of times you see a thrombus in the pulmonary, in the large vessels—but we also see small-capillary thrombus, which isn’t a common phenomenon in most pulmonary embolisms seen before COVID-19,” she explained.

A Fast-Evolving Field

With respect to widespread thromboprophylaxis, there are downsides, primarily bleeding, and there is yet no way to identify the patients at highest risk of VTE, said Sethi. Given how big the problem is, a number of clinical trials are testing various thromboprophylaxis strategies in COVID-19, among them ATTACC, INSPIRATION, IMPROVE-COVID, and FREEDOM COVID-19.

Just a few weeks ago, researchers published observational data from a large series of more than 4,300 adults with confirmed COVID-19 admitted to the Mount Sinai Hospital system. When compared to patients who didn’t receive anticoagulation, therapeutic and prophylactic anticoagulation was associated with a lower risk of mortality and a lower risk of intubation.

Valentin Fuster, MD (Icahn School of Medicine at Mount Sinai, New York), that paper’s senior author and a panelist during today’s TCT session, said he was approached early in the pandemic to conduct an anticoagulation study in patients with COVID-19 but refused because the research question wasn’t clear. Nor was he certain which anticoagulants to study and at what doses. In their observational study, therapeutic- and prophylactic-dose low-molecular-weight heparin, as well as apixaban (Eliquis; Bristol-Myers Squibb), came out on top and this led to the launch of FREEDOM COVID-19 trial, said Fuster.

For Sethi, the anticoagulant dose prescribed for hospitalized COVID-19 patients needs to be determined on a case-by-case basis, with a strong preference for an intermediate dose. In-hospital, said Fuster, they provide anticoagulation to all patients. “Again, this is based on observational studies and it’s my point of view,” he stressed. “I respect people who’d want to use a placebo in a trial, but certainly I would not.”

In patients who’ve left the hospital, Fuster and Sethi said they’d be reluctant to prescribe anticoagulation given the absence of data. Fuster said they are currently following approximately 6,000 patients discharged after a confirmed diagnosis of COVID-19 yet have seen no evidence of thrombosis, at least in the first couple of months.

Sahil Parikh, MD (NewYork-Presbyterian/Columbia University Irving Medical Center), who moderated the session along with Timothy Henry, MD (The Christ Hospital, Cincinnati, OH), observed that despite TCT’s traditional focus on devices and interventions, organizers would be remiss not to address the elephant in the cath lab.

“In this year where we are not meeting in person, but rather virtually because of COVID-19, it would be incomplete of us not to cover this topic,” said Parikh.