Catheter-Directed Thrombolysis exhibits impressive results in patients with Intermediate-Risk Pulmonary Embolism: JAMA

IRAN: In the small randomized CANARY trial, which was reported in JAMA Cardiology, a modified reperfusion procedure for intermediate-risk pulmonary embolism (PE) appeared to be effective without leading to significant bleeding.

Reperfusion therapy is debatable for people with intermediate- to high-risk PE owing to the danger of bleeding. This population is varied and challenging to manage. On the contrary, systemic thrombolysis is recommended in clinical practice for high-risk patients unless it is contraindicated by a significant risk of bleeding.

The researchers noted that "the present review indicated a more positive persistent effect for standard CDT compared with anticoagulation monotherapy on several 3-month imaging markers."

"Future research should ascertain if these hypothesized imaging modifications result in any appreciable improvements in clinical outcomes," they added.

The purpose of the study was to compare the effectiveness of anticoagulation monotherapy versus conventional catheter-directed thrombolysis (cCDT) in optimizing echocardiographic measurements of the right ventricle to left ventricle ratio in acute intermediate-high-risk PE.

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 that was carried out in 2 significant cardiovascular centers in Tehran, Iran, between December 22, 2018, and February 2, 2020. Heparin and cCDT (alteplase, 0.5 mg/catheter/h for 24 hours) were given to participants at random, as opposed to anticoagulation alone. The primary outcome was determined by a core laboratory as the percentage of patients having a 3-month echocardiographic RV/LV ratio higher than 0.9. The proportion of patients having an RV/LV ratio greater than 0.9 at 72 hours following randomization and the 3-month all-cause mortality were among the secondary endpoints. The primary safety result was major bleeding (Bleeding Academic Research Consortium type 3 or 5). Unfortunately, the trial was prematurely terminated due to COVID-19 when the researchers had only enrolled 94 patients, leaving it underpowered to evaluate the primary outcome.

Conclusive points of the trial:

• With cCDT, the median (IQR) 3-month RV/LV ratio was considerably lower (0.7 [0.6-0.7] vs. 0.8 [0.7-0.9]) than with anticoagulation (P =.01).
• More patients treated with anticoagulation (24 of 46 [52.1%]; OR, 0.34; 95% CI, 0.14-0.80; P =.01) than those treated with cCDT (13 of 48 [27.0%]) had RV/LV ratios greater than 0.9 at 72 hours following randomization.
• Patients assigned to cCDT were less likely to encounter a 3-month composite of mortality or an 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).
• The cCDT group experienced one instance of significant gastrointestinal hemorrhage that was not fatal.

The majority of the trial participants, according to Bikdeli and colleagues, had low baseline bleeding risk.

The authors concluded that this prematurely terminated randomized clinical trial of patients with intermediate-high-risk PE served as support for a valid clinical outcomes trial by providing evidence for improvement in some efficacy outcomes and an acceptable rate of vascular events for cCDT particularly in comparison with anticoagulation monotherapy.

"Improved prediction models are also required to recognize PE patients who are most at risk for decompensation and would profit from an early aggressive therapy," they suggested.

REFERENCE

Sadeghipour P, Jenab Y, Moosavi J, et al. Catheter-Directed Thrombolysis vs Anticoagulation in Patients With Acute Intermediate-High–risk Pulmonary Embolism: The CANARY Randomized Clinical Trial. JAMA Cardiol. Published online October 19, 2022. doi:10.1001/jamacardio.2022.3591