Fast versus ultra-slow thrombolytic infusion regimens in patients with obstructive mechanical prosthetic valve thrombosis: a pilot randomized clinical trial

Background Thrombolysis is an alternative to surgery for mechanical prosthetic valve thrombosis (MPVT). Randomized clinical trials have yet to test safety and efficacy of a proposed ultraslow thrombolytic infusion regimen. Methods and Results This single-center, open-label, pilot randomized clinical trial randomized adult patients with acute obstructive MPVT to an ultraslow thrombolytic regimen (25 mg of recombinant tissue-type plasminogen activator [rtPA] infused in 25h) and a fast thrombolytic regimen (50 mg of rtPA infused in 6h). If thrombolysis failed, a repeated dose of 25 mg of rtPA for 6h was administered in both groups up to a cumulative dose of 150 mg or the occurrence of a complication. Primary outcome was a complete MPVT resolution (>75% fall in the obstructive gradient by transthoracic echocardiography, <10° limitation in opening and closing valve motion angles by fluoroscopy, and symptom improvement). Key safety outcome was a BARC type III or V major bleeding. Overall, 120 patients, including 63 (52.5%) women, at a mean age of 36.3±15.3 years, were randomized. Complete thrombolysis success was achieved in 51 patients (85.0%) in the ultraslow-regimen group and 47 patients (78.3%) in the fast-regimen group (OR, 1.58; 95% CI, 0.25 to 1.63; P = 0.34). One case of transient ischemic attack and 3 cases of intracranial hemorrhage (absolute risk difference, −12.5%; 95% CI, −23.1% to −1.0%; P = 0.04). were observed only in the fast-regimen group. Conclusions The ultraslow thrombolytic regimen conferred a high thrombosis resolution rate without major complications. Such findings should be replicated in more adequately powered trials (IRCT20181022041406N2).