Trial Delivers Good News for Pulmonary Embolism Treatment

For patients with intermediate-high-risk acute pulmonary embolism, catheter-directed thrombolysis with alteplase plus anticoagulation therapy led to a lower risk of death from any cause and other adverse outcomes compared with anticoagulation therapy alone, an open-label randomized trial showed.

Among 558 patients, 0.7% in the thrombolysis group experienced a composite endpoint of death from any cause, recurrence of pulmonary embolism, or cardiorespiratory decompensation or collapse within 7 days compared with 6.8% of those receiving standard-care anticoagulation alone (relative risk [RR] 0.10, 95% CI 0.02-0.44, P<0.001), reported Viktor Kocka, MD, PhD, of Charles University in Prague, at the European Society of Cardiology Congress in Munich.

This difference was mainly driven by the lower incidence of cardiorespiratory decompensation or collapse in the thrombolysis group (0.7% vs 5.4%; RR 0.13, 95% CI 0.03-0.57), Kocka and co-authors noted in the New England Journal of Medicine, where the study was published.

No deaths occurred in the thrombolysis group by day 7, while four deaths occurred in the standard-care group. By day 30, there was one death in the thrombolysis group and no deaths in the standard-care group. Recurrence of pulmonary embolism occurred in one patient receiving anticoagulation therapy and in the same two patients receiving thrombolysis who experienced cardiorespiratory decompensation or collapse.

Current practice for intermediate-high-risk acute pulmonary embolism often centers on anticoagulation therapy, with rescue reperfusion used for severe clinical deterioration, the researchers explained. “The results of our trial support the concept that, in selected patients treated in interventional centers, earlier catheter-based reperfusion may prevent deterioration before overt collapse occurs and may facilitate faster recovery,” they wrote.

In-hospital mortality from pulmonary embolism is similar or higher than that for myocardial infarction, ranging from 10% to 20%, Kocka said, yet most patients are treated the same way today that they were three decades ago, with routine anticoagulation, “so there is a big clinical need.”

“I hope that these data, together with the previously published data, will change [upcoming European] guidelines and will completely change the paradigm of our treatment of pulmonary embolism,” he noted. The findings translate to a number needed to treat of 17.

Inderjit Singh, MBChB, MD, director of the Pulmonary Vascular Disease Program at Yale School of Medicine in New Haven, Connecticut, told MedPage Today that he was not surprised that thrombolysis had no effect on pulmonary embolism recurrence, but it was “particularly notable” that the primary outcome was driven by the reduction in cardiorespiratory decompensation/collapse rather than a mortality advantage.

“As a clinician, preventing hemodynamic deterioration in the intermediate-high-risk group is meaningful,” he said. “The primary outcome finding suggests that intervening early in this group of patients may be more effective than waiting to ‘rescue’ patients after the experience of hemodynamic deterioration.”

What gave Singh pause, however, was that the procedure was not risk-free, given two cases of intracranial hemorrhage in the thrombolysis group, and the current lack of data on long-term outcomes, though he remains “cautiously optimistic” about safety. He also noted that the study was conducted in highly organized tertiary centers, raising the question of effectiveness and safety in smaller institutions without access to catheter-directed thrombolysis.

“If these findings are replicated and reflected in future guideline updates, there may be a shift from reactive management towards a more proactive reperfusion strategy in carefully selected intermediate-risk pulmonary embolism patients,” Singh said.

The trial enrolled 558 patients with intermediate-high-risk acute pulmonary embolism from 11 tertiary care cardiovascular centers in the Czech Republic from October 2022 through March 2026. Pulmonary embolism, diagnosed by imaging and lab testing, was defined by hemodynamic stability, a simplified Pulmonary Embolism Severity Index score of at least 1 (scale 0-6), and right ventricular dysfunction plus an elevated level of cardiac troponin or natriuretic peptide.

Median age was 64, 40.9% were women, and 49.5% had been transferred from a referring hospital. Nearly all patients (98.2%) had bilateral pulmonary embolism. Baseline demographic and clinical characteristics were similar in both groups.

Initiation of catheter-directed thrombolysis occurred a median 76 minutes after randomization, and within 3 hours for 89.3% of patients. The alteplase dose was a 1-mg bolus through each catheter, infused at 1 mg per hour per catheter for a total of 20 mg. All but one patient had successful catheter placement and initiation of alteplase infusion, which lasted a mean 9.3 hours per patient.

Patients in both groups received unfractionated or low-molecular-weight heparin before randomization and throughout the trial period. Patients transitioned to oral anticoagulation therapy no sooner than 24 hours after randomization at the treating physician’s discretion.

All patients were followed for 7 days, with 99.3% of thrombolysis patients and 94.6% of anticoagulation-alone patients followed for 30 days.

Looking at secondary outcomes, clinically relevant bleeding occurred in 4.6% of patients in the thrombolysis group versus 5% in the standard-care group by day 7 (P=0.85), while major bleeding occurred in 1.4% and 2.2%, respectively (P=0.54). Intracranial hemorrhage occurred in two patients in the thrombolysis group and no patients in the standard-care group.