Until the ACC/AHA guideline on the management of acute pulmonary embolism (PE) was published in February, more than a decade had passed since the last one. During this interval, catheter-based interventions have expanded substantially, reshaping management of intermediate-risk PE. The optimal role of catheter-based therapies in this population, however, remains an area of active debate.¹

The 2026 ACC/AHA guideline attempts to further refine risk stratification within intermediate-risk PE, a category that encompasses a broad spectrum of clinical presentations. The updated framework introduces a five-tier risk stratification scheme (categories A through E).

Patients previously categorized as intermediate-risk now fall primarily into category C and D, whereas patients with high-risk PE are classified as category E.²

At the time of guideline development, evidence supporting catheter-based therapies for hard clinical outcomes was limited, with most studies relying on surrogate endpoints, such as improvement in right ventricular (RV)/left ventricular (LV) ratio after intervention.^3-5 Data directly comparing catheter-based therapies with anticoagulation alone – the longstanding standard of care – were sparse.

Consequently, the 2026 guideline does not provide strong recommendations for routine catheter-based intervention. Instead, they suggest considering catheter-based therapy in selected higher-risk patients, particularly those corresponding to group D with transient hypotension or evidence of malperfusion.²

Since the writing of the 2026 PE guideline, two randomized trials have compared catheter-based therapy with anticoagulation alone in this population: STORM-PE and HI-PEITHO.

STORM-PE: First RCT of Mechanical Thrombectomy vs. Anticoagulation Alone

The STORM-PE trial evaluated catheter-directed mechanical thrombectomy using the Penumbra Indigo Aspiration System compared with anticoagulation alone in patients with intermediate-risk PE.

Patients undergoing thrombectomy experienced greater improvement in RV/LV ratio at 48 hours and earlier normalization of vital signs with similar rates of major bleeding and adverse events between groups.

Although the study enrolled only 100 patients and was underpowered to evaluate major clinical outcomes, two PE-related deaths occurred in the thrombectomy arm vs. none in the anticoagulation arm. At 90 days, exploratory endpoints suggested greater six-minute walk distance and return to pre-PE functional status with thrombectomy.

HI-PEITHO: CDT vs. Anticoagulation Alone

The larger HI-PEITHO trial more directly evaluated whether catheter-based therapy improves clinically meaningful outcomes. A total of 544 patients with intermediate-risk PE (using prior ESC classification scheme) were randomized to ultrasound-facilitated catheter-directed fibrinolysis (CDT) plus anticoagulation vs. anticoagulation alone. Participants had additional concerning clinical features, including tachycardia, tachypnea or borderline hypotension.

The primary composite outcome of PE-related death, cardiorespiratory decompensation or recurrent PE within seven days occurred less frequently in the CDT group (4.0% vs. 10.3%; p=0.005). Importantly, this difference was driven largely by worsening clinical status, particularly persistent or worsening National Early Warning Scores (NEWS), rather than differences in cardiogenic shock, cardiac arrest, intubation or PE-related death.

Major bleeding was numerically higher with CDT (4.1% vs. 2.2%; p=0.32), with no intracranial hemorrhage in either arm.

Additional findings warrant emphasis. There was no difference in RV/LV ratio on follow-up imaging between treatment arms, contrasting with earlier catheter-based therapy studies.^3-5 Subgroup analyses showed no benefit in patients older than 75 years or with RV/LV ratio <1.5, paralleling findings from the original PEITHO trial of systemic thrombolysis.

Notably, 87% of screened patients were not enrolled, underscoring the highly selected study population. In addition, the protocol mandated randomization within six hours of diagnosis with intervention within two hours thereafter – timelines that may not reflect typical practice.

Clinical Implications and Evidence Gaps

These trials advance the evidence base but do not yet establish catheter-based therapy as standard of care for most intermediate-risk PE. In particular HI-PEITHO also provides important insight into the natural history of patients treated with anticoagulation alone.

Patients managed conservatively with rescue escalation for deterioration did not experience higher rates of cardiogenic shock, cardiac arrest or respiratory failure, supporting watchful waiting with close monitoring for many patients.⁷

The management of acute PE continues to evolve rapidly. Several ongoing trials will further inform practice: PE-TRACT is evaluating catheter-directed therapy with primary endpoints of peak VO₂ at three months and NYHA class at 12 months;⁹ PEERLESS II is comparing large-bore mechanical thrombectomy with anticoagulation alone;¹⁰ and PEITHO-3 is testing reduced-dose systemic fibrinolysis.¹¹

The cornerstone of care remains individualized risk assessment, balancing the likelihood of clinical deterioration against procedural risk. Current evidence suggests that catheter-based therapies may benefit carefully selected patients, while anticoagulation remains sufficient for an overwhelming majority. The critical challenge is identifying the subset of intermediate-high risk patients (group C3 and group D based on the recent ACC/AHA guideline) who may benefit from early intervention – a question that current evidence has begun to address but not yet resolved.

References

1. Jaff MR, McMurtry MS, Archer SL, et al. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension. Circulation. 2011;123:1788-1830.
2. Creager MA, Beckman JA, et al. 2026 AHA/ACC guideline for the management of acute pulmonary embolism. JACC. 2026;87(13):1626-1710.
3. Kucher N, Boekstegers P, Müller OJ, et al. Randomized, controlled trial of ultrasound-assisted catheter-directed thrombolysis for acute intermediate-risk pulmonary embolism. Circulation. 2014;129:479-486.
4. Piazza G, Hohlfelder B, Jaff MR, et al. A prospective, single-arm, multicenter trial of ultrasound-facilitated catheter-directed thrombolysis for acute massive and submassive pulmonary embolism: the SEATTLE II study. JACC Cardiovasc Interv. 2015;8:1382-1392.
5. Tapson VF, Sterling K, Jones N, et al. A randomized trial of the optimum duration of acoustic pulse thrombolysis procedure in acute intermediate-risk pulmonary embolism: the OPTALYSE-PE trial. JACC Cardiovasc Interv. 2018;11:1401-1410.
6. Lookstein RA, Konstantinides SV, Weinberg I, et al. Randomized controlled trial of mechanical thrombectomy with anticoagulation versus anticoagulation alone for acute intermediatehigh risk pulmonary embolism: primary outcomes from the STORM-PE Trial. Circulation. 2026;153:21-34.
7. Rosenfield K, Klok FA, Piazza G, et al. Ultrasound-facilitated, catheter-directed thrombolysis for acute pulmonary embolism. N Engl J Med. 2026;March 28: DOI: 10.1056/NEJMoa2516567.
8. Meyer G, Vicaut E, Danays T, et al. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med. 2014;370:1402-1411.
9. Sista AK, Troxel AB, Tarpey T, et al. Rationale and design of the PE-TRACT trial: A multicenter randomized trial to evaluate catheter-directed therapy for the treatment of intermediate-risk pulmonary embolism. Am Heart J. 2025 Mar;281:112-122.
10. Giri J, Mahfoud F, Gebauer B, et al. PEERLESS II: A randomized controlled trial of large-bore thrombectomy versus anticoagulation in intermediate-risk pulmonary embolism. J Soc Cardiovasc Angiogr Interv. 2024 May 3;3(6):101982.
11. Sanchez O, Meyer G, et al; PEITHO-3 Investigators. Reduced-dose intravenous thrombolysis for acute intermediate-high-risk pulmonary embolism: rationale and design of the Pulmonary Embolism International THrOmbolysis (PEITHO)-3 trial. Thromb Haemost. 2022 May;122(5):857-866.

Clinical Topics: Anticoagulation Management, Vascular Medicine

Keywords: Cardiology Magazine, ACC Publications, CM-Jul-Aug-2026, Pulmonary Embolism, Guidelines as Topic, Interventional Cardiology, Anticoagulation Therapy, Anticoagulants, Catheters