Bilateral lysis of aortic saddle thrombus with early tissue plasminogen activator (BLASTT): a prospective, randomized, placebo-controlled study in feline acute aortic thromboembolism

Abstract

Objectives: The aim of this study was to investigate the impact of tissue plasminogen activator (TPA) on the treatment of feline aortic thromboembolism (FATE).

Methods: Cats diagnosed with FATE involving ⩾2 limbs were enrolled in a prospective, multicenter, double-blinded, randomized, placebo-controlled study within 6 h of an event. Diagnosis was made by clinical findings and one confirmatory criterion. Cats received placebo or TPA (1 mg/kg/h with the first 10% by bolus). All cats received pain control and thromboprophylaxis. The primary outcome was a change from baseline in a published limb score at 48 h. Secondary outcomes included 48 h survival, survival to discharge and complication proportions. Statistical analyses included pattern-mixture models, logistic regression and Fisher's exact, Student's t- and Mann-Whitney-Wilcoxon tests.

Results: Based on a power analysis, 40 cats were enrolled; however, only 20 survived to 48 h (TPA, n = 12; placebo, n = 8 [P = 0.34]). There was a statistically significant improvement in limb scores compared with baseline for both groups (P <0.001). Limb score at 48 h was 1 point lower (better) in the TPA group (P = 0.19). Thrombolysis had no statistically significant effect on 48 h survival (P = 0.22). Lower affected limb lactate was associated with better 48 h survival (odds ratio 1.53, 95% confidence interval 1.08-2.17; P = 0.02). The survival to discharge rates were 45% (TPA) and 30% (placebo; P = 0.51). Complications in the TPA and placebo groups included acute kidney injury (22% and 19%, respectively; P = 1.00) and/or reperfusion injuries (33% and 19%, respectively; P = 0.45).

Conclusions and relevance: Survival and complication rates of acute FATE were not different with or without thrombolysis. High in-hospital mortality decreased the statistical power to detect a statistically significant difference between treatments with regard to our primary outcome.

Keywords: Thrombolysis; alteplase; embolism; ischemic neuropathy; rTPA; thrombosis.

Figure 1

Patient flow diagram for 40 cats diagnosed with feline aortic thromboembolism (FATE) enrolled in a prospective study in a tissue plasminogen activator (TPA) group (20 cats) and saline placebo group (20 cats). *One cat in the TPA group was alive at 48 h but did not get a limb score; one cat in the placebo group had a limb score performed immediately before euthanasia at the 48 h mark

Figure 2

Mean ± SD (vertical lines) for limb scores over 48 h in 40 cats diagnosed with feline aortic thromboembolism (FATE) enrolled in a prospective study in a tissue plasminogen activator (TPA) group (n = 20) and saline placebo group (n = 20 cats). *^$Limb score different over time within the same group (P <0.05). There was no significant difference between the treatments. ▲and straight line = TPA group; ♦ and dashed line = placebo group. The numbers in parenthesis below the various time points represent the number of cats in each group remaining at that time point (TPA/placebo)