2026 ACC/AHA Guideline Introduces Five-Tier Risk Stratification for Acute Pulmonary Embolism, Refining Role of Catheter-Based Interventions
核心洞察
The 2026 ACC/AHA multisociety guideline introduces a five-tier risk stratification scheme (categories A through E) for acute PE, replacing the prior three-tier model and better differentiating patients who may benefit from advanced therapies.
Two recent randomized trials, STORM-PE and HI-PEITHO, compared catheter-based interventions with anticoagulation alone in intermediate-risk PE, showing mixed results on clinical outcomes and raising questions about routine use.
HI-PEITHO demonstrated a reduction in the primary composite outcome (4.0% vs. 10.3%; p=0.005) with ultrasound-facilitated catheter-directed fibrinolysis, though the benefit was driven largely by worsening clinical status rather than hard endpoints like death or cardiogenic shock.
The 2026 ACC/AHA multisociety guideline for the management of acute pulmonary embolism (搜索) (PE), published in February, marks the first comprehensive, multidisciplinary clinical guideline on this condition in the United States. Jointly published in Circulation and the Journal of the American College of Cardiology (搜索), the document was developed by a multispecialty group of 10 medical societies spearheaded by the American Hospital Association (搜索) (AHA) and the American College of Cardiology (ACC). Its central innovation is a five-tier risk stratification framework that refines clinical decision-making for a condition that has long suffered from ambiguous specialty ownership.
"The ESC guidelines divide patients with PE into three risk categories: low, intermediate and high," said Cleveland Clinic vascular medicine physician Leben Tefera, MD, who served on the writing committee. "A general classification system like that makes it hard to know which patients are critically ill and might benefit from evolving technology. We wanted a more clinically appropriate classification that would be helpful in differentiating patients who are stable enough to go home the same day from those who are very sick. Now we have it."
A Five-Tier Risk Stratification Framework
The updated classification system consists of five clinical categories ranging from lowest risk (A) to highest risk (E) for adverse outcomes, with categories further divided into subcategories. Patients in Categories A and B have no or mild symptoms and a low risk of severe complications; they typically can be safely discharged from the emergency department. Categories C through E include patients with symptoms of acute PE who are at higher risk of adverse outcomes and require hospitalization.
Patients previously categorized as intermediate-risk under the older three-tier system now fall primarily into categories C and D, while patients with high-risk PE are classified as category E. This granularity, according to Aravinda Nanjundappa, MBBS, MD, an interventional cardiologist at Cleveland Clinic, moves beyond the traditional "stable versus unstable" model and better reflects the spectrum of disease severity seen in clinical practice. "From the perspective of an interventional cardiologist, it helps identify patients who may benefit from advanced therapies while avoiding unnecessary procedures in lower-risk patients, ultimately improving patient care and future clinical trial design," he observed.
Catheter-Based Interventions: Evidence and Uncertainty
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. 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, it suggests considering catheter-based therapy in selected higher-risk patients, particularly those corresponding to group D with transient hypotension or evidence of malperfusion.
Since the guideline's writing, two randomized trials have provided new comparative data: STORM-PE and HI-PEITHO.
STORM-PE: Mechanical Thrombectomy Versus Anticoagulation
The STORM-PE trial evaluated catheter-directed mechanical thrombectomy using the Penumbra Indigo Aspiration System (搜索) 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. However, the study enrolled only 100 patients and was underpowered to evaluate major clinical outcomes. Notably, two PE-related deaths occurred in the thrombectomy arm versus 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: Catheter-Directed Fibrinolysis Versus Anticoagulation
The larger HI-PEITHO trial randomized 544 patients with intermediate-risk PE to ultrasound-facilitated catheter-directed fibrinolysis (CDT) plus anticoagulation versus 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.
Several 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. Subgroup analyses showed no benefit in patients older than 75 years or with RV/LV ratio less than 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. The protocol also mandated randomization within six hours of diagnosis with intervention within two hours thereafter—timelines that may not reflect typical practice.
Clinical Implications and the Path Forward
These trials advance the evidence base but do not yet establish catheter-based therapy as standard of care for most intermediate-risk PE. 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.
The guideline also provides a level 1 recommendation for assessment by a pulmonary embolism response team (PERT) for patients in Categories C through E. Cleveland Clinic's multidisciplinary PERT, operational since 2016, comprises specialists in vascular medicine, pulmonology, critical care medicine, cardiology, and interventional radiology. "We see patients very rapidly after they are diagnosed, and again within four weeks after they are discharged," Dr. Tefera noted. "We evaluate them for ongoing need for anticoagulation, appropriateness of the anticoagulant, and when to stop anticoagulation."
Another major change in the guideline is that low-molecular-weight heparin has replaced unfractionated heparin as a level 1 recommendation for initial parenteral anticoagulation in patients in Categories C1 through E1.
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; PEERLESS II is comparing large-bore mechanical thrombectomy with anticoagulation alone; and PEITHO-3 is testing reduced-dose systemic fibrinolysis. The critical challenge remains identifying the subset of intermediate-high risk patients—group C3 and group D based on the ACC/AHA guideline—who may benefit from early intervention, a question that current evidence has begun to address but not yet resolved.