Weighing Bleeding Risk in Pulmonary Embolism, With Samantha Pettigrew, MD

At CHEST 2026 in Phoenix, Samantha Pettigrew, MD, a pulmonary and critical care physician at Temple University Hospital, urged clinicians to look past imaging endpoints in pulmonary embolism trials and weigh bleeding risk and functional recovery when selecting advanced therapies for intermediate-risk pulmonary vascular disease.¹

Pettigrew presented “Pulmonary Embolism Care in 2026: New Randomized Clinical Trials and What’s Coming Next” as part of the Pulmonary Vascular Disease Section programming.¹ Catheter-based thrombolysis and mechanical thrombectomy have spread rapidly in intermediate-risk pulmonary embolism (PE), and many devices reached practice on the strength of safety data and imaging measures such as clot burden. In an interview with HCPLive, Pettigrew said imaging gains alone do not establish the size of the clinical benefit or whether an invasive intervention outperforms anticoagulation.

“Is it better than just giving the patient a blood thinner or anticoagulation to begin with? Those are things trials don’t tell us if they just have an imaging endpoint,” Pettigrew said.

Low-Dose Alteplase and Ultrasound-Assisted Thrombolysis in STRATIFY

Pettigrew highlighted the STRATIFY trial, an open-label, multicenter randomized trial conducted in Denmark.² The team randomized 210 patients with acute intermediate-high-risk PE 1:1:1 to 20 mg alteplase infused across 6 hours via ultrasound-assisted thrombolysis (USAT) (n = 71), the same dose delivered intravenously (n = 70), or heparin alone (n = 69).² The primary end point was change in the refined modified Miller score (rmMS), a CT angiography measure of thrombus burden, at 48 to 96 hours.²

Low-dose thrombolysis reduced the rmMS by 3.6 points compared with heparin alone ((95% CI 2.2–5.0, P < 0.001).² Delivery by USAT added no clot reduction compared with the intravenous route (mean difference, −0.1; 95% CI, −1.9 to 1.7; P =.88).²

Pettigrew said the bleeding signal was not unexpected, given the concern pulmonologists and intensivists carry any time they administer tissue plasminogen activator (tPA). Unless a patient is rapidly deteriorating, she recommended reviewing every absolute and relative contraindication to tPA before treatment. She noted the review takes only a few minutes, and she sometimes pulls the list up on her phone.

Pettigrew also stressed confirming both the clinician and the patient understand the bleeding risk before treatment when the clinical scenario allows time for the discussion.

Functional Outcomes After Mechanical Thrombectomy in STORM-PE

Pettigrew said mechanical thrombectomy has become increasingly prevalent, in part because removing the clot feels as though it offers the fastest route to recovery. STORM-PE enrolled 100 patients with acute intermediate-high risk PE at 22 international sites and compared computer-assisted vacuum thrombectomy (CAVT) with Penumbra’s Lightning Flash system plus anticoagulation against anticoagulation alone.³

At 90 days, patients in the CAVT arm walked farther on the 6-minute walk test (479 m vs 368 m; P =.003) and reached 94% of predicted distance compared with 75.2% in the anticoagulation arm (P =.022).³ A greater proportion of CAVT-treated patients reported no physical limitation by New York Heart Association (NYHA) functional class (97% vs 76%; P =.022).³ Safety through 90 days was comparable between arms, with no device-related deaths.³

Pettigrew called these among the first randomized functional data in the field, addressing whether patients can return to normal life rather than simply survive hospitalization and avoid feared bleeding outcomes.

Looking Ahead in Pulmonary Embolism

She said she is most anticipating PEERLESS II, a prospective, multicenter randomized trial comparing the FlowTriever system plus anticoagulation with anticoagulation alone in intermediate-risk PE.⁴ For patients who do not fit neatly into a guideline category, Pettigrew advised developing a plan together with colleagues, PE specialists, and interventionalists.

“No matter how many trials we do, no matter how many papers we write, you’re never going to come up with a guideline for every single use case,” said Pettigrew. “Treat the patient in front of you, not the guidelines.”

Watch part 1 here: New Trials Favor PE Intervention in Sicker Intermediate-Risk Patients

Editor’s note: A reported disclosure for Pettigrew includes Inari Medical.

References

1. Pettigrew S. Pulmonary embolism care in 2026: new randomized clinical trials and what’s coming next. Presented at CHEST 2026; October 18-21, 2026; Phoenix, AZ.

2. Kjaergaard J, Bang LE, Sonne-Holm E, et al. Randomized trial of low-dose, ultrasound-assisted thrombolysis or heparin for pulmonary embolism. Cardiovasc Res. 2026;122(4):539-549. doi:10.1093/cvr/cvag038

3. Kay B. New STORM-PE data show improved functional outcomes with CAVT plus anticoagulation. Vascular News. Published April 14, 2026. Accessed October 20, 2026. https://vascularnews.com/new-storm-pe-data-show-improved-functional-outcomes-with-cavt-plus-anticoagulation/

4. The PEERLESS II Study. ClinicalTrials.gov identifier: NCT06055920. Accessed October 20, 2026. https://clinicaltrials.gov/study/NCT06055920