As COVID-19-related incidences of VTE have increased clinical awareness of thromboembolism, questions remain about how to manage the condition even in non-COVID situations.
During the CHEST 2022 discussion session, Controversial Issues in VTE Management, on Wednesday, October 19, panelists reviewed the latest guidance on the role of key treatments in patients with VTE: anticoagulants and antiplatelet agents, systemic thrombolysis for intermediate-risk acute pulmonary embolism (PE), and catheter-directed thrombolysis.
These topics deserve continued attention from physicians because they are in flux and will undergo frequent changes, said Session Chair, Lisa Moores, MD, FCCP, senior author of CHEST’s 2021 VTE guideline update.
The role of anticoagulants and antiplatelets
In the population of patients with COVID-19 and VTE, researchers are investigating the role and dosing of standard and novel anticoagulants, such as heparin; antiplatelet drugs, such as aspirin or clopidogrel; and fibrinolysis with a tissue plasminogen activator (tPA), said Vijay Balasubramanian, MD, FCCP, clinical professor of medicine at UCSF Fresno and chair of CHEST’s Pulmonary Vascular Disease Section.
Anticoagulants have been shown to lower mortality in patients hospitalized with COVID-19, with an adaptive randomized study suggesting the strategy is superior to usual care. Amid debate about when and how anticoagulants should be given, the ACTION trial has generated data in favor of prophylactic vs therapeutic treatment.
That doesn’t benefit critically ill patients, who may better respond to treatment with a tPA before anticoagulation, Dr. Balasubramanian said. In the STARS study, tPA followed by 7 days of therapeutic heparin improved oxygenation in intubated patients with severe COVID-19 respiratory failure.
“The pendulum has swung since the onset of COVID,” he said. “Initially, we thought therapeutic anticoagulation was very helpful in critically ill patients; whereas, by 2022, we have learned that therapeutic anticoagulation in critically ill patients is probably harmful.”
Less clear is the role of antiplatelet agents, Dr. Balasubramanian said. Adding an antiplatelet inhibitor to anticoagulant treatment has not demonstrated effectiveness, and a study showed that aspirin did not reduce mortality or the risk of invasive mechanical ventilation in hospitalized patients with COVID-19, although it was associated with a small increase in their likelihood of being discharged alive within 28 days.
Selecting patients for tPA
Frontline thrombolysis is not reserved for critically ill patients, as some with intermediate-risk, or submassive, PE may benefit, said Bhavinkumar Dalal, MBBS, MD, FCCP, associate professor at Oakland University’s William Beaumont School of Medicine.
Because intermediate PEs confer a mortality rate of 3% to 20%, they may respond to tPA, Dr. Dalal said. Patients in this population with “a mortality probability in the double digits” are the most likely to benefit, he said.
Dr. Dalal listed five “D’s” that indicate when thrombolytic therapy might be appropriate for patients with intermediate PEs:
- Diameter with a right ventricle (RV)/left ventricle (LV) ratio as high as 1.4 or 1.5
- Deep vein thrombosis that is proximal and associated with PE
- Data, particularly borderline low blood pressure, high lactate, and significant hypoxia
- Diseases, specifically comorbid COPD and/or congestive heart failure
- Deterioration that appears 24 to 48 hours after treatment has begun
Dr. Dalal suggested researching each patient’s typical blood pressure, as any drop of 40 points or more constitutes hypotension—even if systolic pressure remains above 90 mm Hg.
Selecting patients for catheter-directed thrombolysis
Thrombolytic therapy is typically administered systemically for patients with acute PE, but what are the advantages to catheter-directed intervention, and when is it appropriate?
While systemic tPA reduces the risk of mortality and hemodynamic decompensation compared with anticoagulation, it creates an “unacceptable” incidence of bleeding, even in clinical trial populations selected for their low bleeding risk, said Parth Rali, MD, associate professor at the Lewis Katz School of Medicine at Temple University Hospital.
Catheter-directed thrombolysis (CDT) can be a good alternative when anticoagulation is not sufficient to treat intermediate-risk PE, Dr. Rali said. It administers doses 5 to 10 times lower, yet more durable, than tPA infusions and is associated with a much lower rate of bleeding. Administered with or without ultrasound guidance using small- or large-bore suction or pharmacomechanical catheters, CDT improves patients’ RV/LV ratio by 25% to 30% at 48 hours, he said.
To select patients, Dr. Rali suggested combining data from predictive bleeding risk scoring systems. Characteristics that increase bleeding risk include cerebrovascular accident, advanced age, cancer, syncope, a history of bleeds, anemia, an abnormal creatinine/glomerular filtration rate, and many more.
“CDT takes time, a lot of coordination, and we need to plan early,” he cautioned. “The decision is easy; execution is still difficult and challenging. Sometimes we say, ‘Use the CDT when things are failing,’ but then, that may be too late.”