Ms. Jang
Clinical question: Do patients with acute intermediate-high-risk pulmonary embolism (PE) benefit more in terms of cardiac function from reperfusion therapy with conventional catheter-directed thrombolysis (cCDT) plus anticoagulation, or does monotherapy anticoagulation have the similar outcomes?
Background: The role of reperfusion therapy in intermediate-high-risk PE is still debated. Rather than full-dose systemic fibrinolytic therapy, which raises concerns for increased bleeding events, this study explores whether a smaller-dose catheter-directed approach (cCDT) delivered into the pulmonary arteries, followed by anticoagulation therapy, can reduce bleeding events caused by systemic therapy and provide overall improved cardiac function. However, there is little existing evidence to suggest that a combination of cCDT and anticoagulation therapy is superior to monotherapy anticoagulation.
Study design: Randomized clinical trial
Setting: Two large cardiovascular centers in Tehran, Iran from December 22, 2018, through February 2, 2020.
Synopsis: This was a randomized clinical trial of 94 patients called the CANARY Trial (Catheter-Directed Thrombolysis versus Anticoagulation Monotherapy in Patients With Acute Intermediate-High-Risk Pulmonary Embolism). Patients were randomly assigned to receive either cCDT (alteplase, 0.5 mg/catheter/h for 24 hours) plus heparin followed by anticoagulation therapy (n=48) or anticoagulation monotherapy (n=46). For both groups, anticoagulation was defined as twice-daily subcutaneous enoxaparin 1 mg/kg, and transition to oral anticoagulation was permissible at the discretion of treating clinicians. The primary endpoint was determined by achieving greater than a 0.9 right ventricle/left ventricle (RV/LV) ratio measured by transthoracic echocardiography at the three-month follow-up. The outcomes of the trial were that numerically fewer cCDT patients (4.3%) had over a 0.9 RV/LV ratio than those in the monotherapy group (12.8%). Notably, all three deaths in the study occurred in the monotherapy group and one gastrointestinal (non-fatal) bleed occurred in the cCDT group. While treatment of intermediate-high-risk PE with cCDT did not achieve a statistically significant reduction in the percentage of patients with an RV/LV ratio greater than 0.9, it did improve echocardiographic markers of RV recovery.
Limitations: The trial ended prematurely due to the COVID-19 pandemic. Additionally, only 85 of the 94 enrolled participants returned for their three-month follow-up transthoracic echocardiogram. Also, women were underrepresented (30%).
Bottom line: Due to premature termination, the study was not able to decipher significant differences between cCDT and anticoagulation monotherapy. There does not appear to be a clear mortality benefit nor a high risk of bleeding with cCDT in this patient population. Larger studies with longer follow-ups will be needed to assess whether cCDT benefits long-term RV function in patients with intermediate-high-risk PE.
Citation: Sadeghipour P, Jenab Y, et al. Catheter-directed thrombolysis vs anticoagulation in patients with acute intermediate-high–risk pulmonary embolism: the CANARY randomized clinical trial. JAMA Cardiol. 2022;7(12):1189-97.
Ms. Jang is a hospitalist nurse practitioner on an inpatient oncology/medicine primary team at Stanford Health Care in Palo Alto, Calif.