Catheter-Directed Thrombolysis vs Anticoagulation in Patients With Acute Intermediate-High–risk Pulmonary Embolism
Authors: Sadeghipour Parham , Jenab Yaser , Moosavi Jamal , Hosseini Kaveh , Mohebbi Bahram , Hosseinsabet Ali , Chatterjee Saurav , Pouraliakbar Hamidreza , Shirani Shapour , Shishehbor Mehdi H. , Alizadehasl Azin , Farrashi Melody , Rezvani Mohammad Ali , Rafiee Farnaz , Jalali Arash , Rashedi Sina , Shafe Omid , Giri Jay , Monreal Manuel , Jimenez David , Lang Irene , Maleki Majid , Goldhaber Samuel Z. , Krumholz Harlan M. , Piazza Gregory , Bikdeli Behnood 
Published: October 2022

Importance

The optimal treatment of intermediate-high–risk pulmonary embolism (PE) remains unknown.

Objective

To assess the effect of conventional catheter-directed thrombolysis (cCDT) plus anticoagulation vs anticoagulation monotherapy in improving echocardiographic measures of right ventricle (RV) to left ventricle (LV) ratio in acute intermediate-high–risk PE.

Design, Setting, and Participants

The Catheter-Directed Thrombolysis vs Anticoagulation in Patients with Acute Intermediate-High–Risk Pulmonary Embolism (CANARY) trial was an open-label, randomized clinical trial of patients with intermediate-high–risk PE, conducted in 2 large cardiovascular centers in Tehran, Iran, between December 22, 2018, through February 2, 2020.

Interventions

Patients were randomly assigned to cCDT (alteplase, 0.5 mg/catheter/h for 24 hours) plus heparin vs anticoagulation monotherapy.

Main Outcomes and Measures

The proportion of patients with a 3-month echocardiographic RV/LV ratio greater than 0.9, assessed by a core laboratory, was the primary outcome. The proportion of patients with an RV/LV ratio greater than 0.9 at 72 hours after randomization and the 3-month all-cause mortality were among secondary outcomes. Major bleeding (Bleeding Academic Research Consortium type 3 or 5) was the main safety outcome. A clinical events committee, masked to the treatment assignment, adjudicated clinical outcomes.

Results

The study was prematurely stopped due to the COVID-19 pandemic after recruiting 94 patients (mean [SD] age, 58.4 [2.5] years; 27 women [29%]), of whom 85 patients completed the 3-month echocardiographic follow-up. Overall, 2 of 46 patients (4.3%) in the cCDT group and 5 of 39 patients (12.8%) in the anticoagulation monotherapy group met the primary outcome (odds ratio [OR], 0.31; 95% CI, 0.06-1.69; P = .24). The median (IQR) 3-month RV/LV ratio was significantly lower with cCDT (0.7 [0.6-0.7]) than with anticoagulation (0.8 [0.7-0.9); P = .01). An RV/LV ratio greater than 0.9 at 72 hours after randomization was observed in fewer patients treated with cCDT (13 of 48 [27.0%]) than anticoagulation (24 of 46 [52.1%]; OR, 0.34; 95% CI, 0.14-0.80; P = .01). Fewer patients assigned to cCDT experienced a 3-month composite of death or RV/LV greater than 0.9 (2 of 48 [4.3%] vs 8 of 46 [17.3%]; OR, 0.20; 95% CI, 0.04-1.03; P = .048). One case of nonfatal major gastrointestinal bleeding occurred in the cCDT group.

Conclusions and Relevance

This prematurely terminated randomized clinical trial of patients with intermediate-high–risk PE was hypothesis-generating for improvement in some efficacy outcomes and acceptable rate of major bleeding for cCDT compared with anticoagulation monotherapy and provided support for a definitive clinical outcomes trial.

Trial Registration

ClinicalTrials.gov Identifier: NCT05172115