Tenecteplase may be a safe and effective alternative to alteplase in patients with obstructive mechanical prosthetic heart valve thrombosis, findings of a randomised clinical trial comparing the two thrombolytic therapies has shown.
Gautam Sharma (All India Institute of Medical Sciences, New Delhi, India) and colleagues report the findings of their study, involving 83 patients with obstructive prosthetic heart valve thrombosis, in a paper published this month in JAMA Cardiology.
The investigators found that patients with obstructive prosthetic valve thrombosis had higher rates of complete thrombolytic success, a shorter duration of hospital stay, and similar adverse events with tenecteplase as compared with alteplase.
The optimal treatment approach for obstructive valve thrombosis remains controversial, Sharma et al write in their JAMA Cardiology paper, acknowledging that evidence suggests thrombolytic therapy is a safe alternative to surgery. Slow infusion of low-dose alteplase is seen as the thrombolytic agent of choice, with success rates of 85–90%, but the fibrin specificity of tenecteplase has contributed to its efficacy in conditions such as ischaemic stroke. The thrombolytic agent has, anecdotally, been considered safe, they write, but its comparison to the standard of care remains unevaluated.
The study, an open-label, parallel-group randomised clinical trial conducted at the All India Institute of Medical Sciences, saw patients receive either a low-dose slow infusion of alteplase or weight-based bolus doses of tenecteplase. Echocardiographic normalisation of valve haemodynamics, symptomatic improvement, and fluoroscopic leaflet motion normalisation were the criteria used to assess efficacy. Complete success was achieved when all three criteria were met, and partial success was achieved when two of three criteria were met.
The investigators anticipated an absolute difference in effect size of 5% in favour of tenecteplase. As a conservative estimate, they assumed an absolute difference of 2.5% and a non-inferiority margin that would preserve 40% of alteplase’s efficacy.
Eighty-three patients, with an average age of just over 39 years, were randomised to receive either strategy, 40 receiving tenecteplase and 43 alteplase. The investigators found that tenecteplase was non-inferior to alteplase with regard to the primary efficacy outcome, with complete thrombolytic success occurring in 97.5% of patients in the tenecteplase group and 81.4% of patients in the alteplase group. Overall thrombolytic success stood at 97.5% in the tenecteplase group compared to 90.7% for alteplase. Additionally, patients receiving alteplase had a longer median duration of hospital stay.
“Our patients in either group had high rates of thrombolytic success and a low rate of complications,” the authors write. “A concern with accelerated thrombolysis was the proposed increased risk of embolism, especially in large thrombi. We encountered much lower rates of embolism than previously reported, speaking to the safety of fibrin-specific thrombolytics.”
Some study limitations are highlighted by the authors in their JAMA Cardiology paper, notably the open-label design and exclusion of patients with cardiogenic shock, as well as only a minority having New York Heart Association (NYHA) class IV symptoms, making it difficult to extrapolate results to these subgroups. Furthermore, the study lacks long-term follow-up, limiting assessment of late complications, and most patients were young with a low bleeding risk. “Whether the therapeutic benefit would translate to an older population remains unknown,” they state.
“In this randomised clinical trial comparing tenecteplase with alteplase in patients with obstructive thrombosis of mechanical prosthetic valves, we found tenecteplase to be non-inferior with regard to thrombolytic success,” the authors write in their concluding remarks. “Patients treated with tenecteplase had higher rates of complete success with the first dose and a shorter duration of hospitalisation.”
