Catheter-Directed Thrombolysis vs Anticoagulation in Patients With Acute Intermediate-High–risk Pulmonary Embolism

Abstract

ImportanceThe optimal treatment of intermediate-high–risk pulmonary embolism (PE) remains unknown.ObjectiveTo 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 ParticipantsThe 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.InterventionsPatients were randomly assigned to cCDT (alteplase, 0.5 mg/catheter/h for 24 hours) plus heparin vs anticoagulation monotherapy.Main Outcomes and MeasuresThe 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.ResultsThe 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 RelevanceThis 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 RegistrationClinicalTrials.gov Identifier: NCT05172115

Interventional therapies for pulmonary embolism

“…In the open-label, randomized CANARY trial 110 , CDT using the Cragg–McNamara catheter was compared with anticoagulation alone in patients with intermediate–high-risk PE (Table 4 ). Patients in the CDT group received either 12 mg alteplase (unilateral PE) or 24 mg alteplase (bilateral PE) over 24 h. Patients in the anticoagulation group received enoxaparin (1 mg/kg twice daily).…”

“…In total, three patients died, all of whom were in the anticoagulation group. In summary, the CANARY trial 110 is the largest RCT to date comparing CDT against anticoagulation, but the trial was underpowered and prematurely stopped, so the findings should be regarded as hypothesis-generating only.…”

“…Some of these interventional therapies have been shown to reduce RVD 110 , 120 , 128 , 131 , 132 , an indicator of early mortality in patients with PE 61 , 75 , 147 . However, most of these data are derived from observational and retrospective studies that were not adequately powered to assess the effect on clinical end points and did not have an appropriate control group.…”

Catheter-Directed Treatment of Submassive Pulmonary Embolism—A Cautious Step Closer?

“…Despite the small size of the CANARY trial, several findings are noteworthy, particularly the low rate of major hemorrhage. It is doubtful that this result is solely attributable to the locally delivered reduced dose of thrombolytic therapy, as the lower bleeding risk of the patients enrolled (mean age, 58 years) may also be a major factor.…”

“…[1][2][3] However, use of thrombolytic therapy for intermediaterisk or submassive pulmonary embolism, defined by right ventricular dysfunction without hemodynamic compromise, remains controversial due to the high risk of bleeding, including intracranial bleeding, associated with this treatment. [2][3][4] Sadeghipour and colleagues 5 report results from the Catheter-Directed Thrombolysis vs Anticoagulation in Patients With Acute Intermediate-High-Risk Pulmonary Embolism (CANARY) randomized clinical trial. The trial was designed as an open-label randomized assessment of conventional catheter-directed thrombolysis (cCDT) plus anticoagulation vs anticoagulation monotherapy in improving echocardiographic measures, specifically the right ventricle to left ventricle (RV/LV) ratio, measured at 3 months.…”