Catheter-directed fibrinolysis safe in intermediate-high-risk pulmonary embolism
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In adults with intermediate-high-risk pulmonary embolism, catheter-directed fibrinolysis plus anticoagulation appears safe and was associated with favorable imaging-based findings compared with anticoagulation monotherapy, data show.
“Our results are not practice-changing for now, but the safety of the intervention is noteworthy, particularly when considered in pooled analyses along with prior trials,” Behnood Bikdeli, MD, MS, instructor in medicine at Harvard Medical School and an associate physician at the division of cardiovascular medicine at Brigham and Women’s Hospital, told Healio. “Because of ongoing equipoise, I encourage clinicians and patients to consider enrollment in one of the several ongoing outcomes trials so that all of us can stop guessing and have high-quality knowledge about optimal management strategies in intermediate-high-risk PE.”
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Assessing RV/LV ratio
For the CANARY trial, Bikdeli and colleagues assessed the effect of conventional catheter-directed thrombolysis plus anticoagulation vs. anticoagulation monotherapy in improving echocardiographic measures of right ventricle to left ventricle ratio in acute intermediate-high-risk PE. The study was conducted in two large CV centers in Tehran, Iran, between December 2018 and February 2020. Researchers randomly assigned participants to conventional catheter-directed thrombolysis plus anticoagulation (alteplase [Activase, Genentech], 0.5 mg/catheter/hour for 24 hours) plus heparin vs. anticoagulation monotherapy. The primary outcome was the proportion of patients with a 3-month echocardiographic RV/LV ratio greater than 0.9, assessed by a core laboratory. Secondary outcomes included the proportion of patients with an RV/LV ratio greater than 0.9 at 72 hours after randomization and 3-month all-cause mortality. Researchers also assessed major bleeding.
The findings were published in JAMA Cardiology.
The study was prematurely stopped due to the COVID-19 pandemic after recruiting 94 participants (mean age, 58 years; 29% women), of whom 85 completed the 3-month echocardiographic follow-up.
Improved echocardiographic measures
Within the cohort, 4.3% of participants in the conventional catheter-directed thrombolysis group and 12.8% in the anticoagulation monotherapy group met the primary outcome, for an OR of 0.31 (95% CI, 0.06-1.69; P = .24). The median 3-month RV/LV ratio was significantly lower with conventional catheter-directed thrombolysis (0.7; 95% CI, 0.6-0.7) than with anticoagulation monotherapy (0.8; 95% CI, 0.7-0.9; P = .01).
Researchers observed an RV/LV ratio greater than 0.9 at 72 hours after randomization in fewer patients treated with conventional catheter-directed thrombolysis (27%) than with anticoagulation monotherapy (52.1%; OR = 0.34; 95% CI, 0.14-0.8; P = .01). Fewer patients assigned to conventional catheter-directed thrombolysis experienced death or RV/LV greater than 0.9 at 3 months (4.3% vs. 17.3%; OR = 0.2; 95% CI, 0.04-1.03; P = .048).
Researchers observed one case of nonfatal major gastrointestinal bleeding in the conventional catheter-directed thrombolysis group.
“There are several lines of research to be pursued,” Bikdeli told Healio. “From a comparative effectiveness standpoint, we are anxiously waiting the completion of several large, randomized trials that test various forms of catheter-directed therapies, including fibrinolysis and thrombectomy, or even low-dose systemic fibrinolysis. We also need more effective tools to allow for better prognostication of these patients. As is, ‘intermediate-high risk’ is a meaningful category but very heterogenous. We need to do a better job finding patients who do well, and those who are more likely to decompensate, thereby being better candidates for advanced therapies.”
Bikdeli said more research is also needed to determine whether certain therapies are better suited for particular patient subgroups.
“We need to understand the trade-offs not only for short-term outcomes, but also durable outcomes including mortality, bleeding and recurrent venous thrombosis, as well as patient-reported outcomes such as persistent dyspnea, quality of life and functional capacity,” Bikdeli said.
Longer-term data needed
In a related editorial, Elaine Hylek, MD, MPH, professor of medicine at Boston University School of Medicine, wrote that several of the study findings are noteworthy despite the small size of CANARY, 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,” Hylek wrote.
Hylek added that well-designed trials are needed to guide clinical practice in patient selection, optimal dose, timing of intervention and effective mode of delivery, given the heightened risk for mortality among patients with submassive PE.
“Importantly, the investigators were able to demonstrate efficacy with the dose of catheter-directed alteplase used in this study,” Hylek wrote. “Whether or not the RV/LV ratio and degree of change over time can be extrapolated to meaningful longer-term improvement in patient exercise capacity and quality of life awaits further study.”
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For more information:
Behnood Bikdeli, MD, MS, can be reached at behnood.bikdeli@yale.edu; Twitter: @bbikdeli.
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