Slow/ultraslow low-dose thrombolytic therapy for mechanical prosthetic valve thrombosis: a multicenter patient-level pooled analysis
P Sadeghipour, A Guner, S Gunduz, M Kalcik, M MozafaryBazargany, E Kohansal, M Farrashi, O M Gursoy, M Yesin, E Bayam, S Kalkan, R De Caterina, M OzkanAbstract
Background
Despite the apparent emerging success of new thrombolytic regimens in the treatment of mechanical prosthetic valve thrombosis (MPVT), all available studies had small-to-moderate sample sizes, affecting the reliability of individual findings.
Purpose
To perform a patient-level pooled analysis, enabling a multi-center/multi-national investigation of slow/ultraslow low-dose thrombolysis in MPVT; to estimate its efficacy and safety; and to identify predictors of thrombolytic success.
Methods
Our systematic search was limited to prospective studies with at least 10 patients each, testing slow/ultraslow low-dose thrombolysis (i.e., low-dose tissue plasminogen activator (tPA) (i.e., 25 mg) during a 6-hour (slow) or 25-hour (ultraslow) period, repeated - if necessary – up to the maximum dose of 150-200 mg) in the treatment of acute MPVT. The main efficacy and safety outcomes were complete thrombotic resolution and major bleeding. Other outcomes were first-session success, in-hospital mortality (IHM), and cerebral and peripheral thromboembolic events. Pre-specified predictors of success were assessed using multivariable logistic regression.
Results
Authors of two out of nine originally selected studies did not respond to the formal invitation to contribute to patient-level data: one study recruiting pregnant women was excluded (Table 1). After eliminating overlapping patients between studies, 558 episodes of MPVT were found in 540 patients (mean age 44 ± 15 years; 363 (65%) were female); the mitral valve was the most affected valve, 80.7% were obstructive MPVT based on study definition, and 33.5% of patients presented with NYHA ≥III. Overall, thrombosis resolution was achieved in 490/558 episodes (87.8%), with a first-session success in 192/555 (34.6%). Median number of tPA repeats was 2 [IQR 1–3]; mean total dose was 60.7 ± 38.8 mg. IHM occurred in 12/558 episodes (2.1%); bleeding in 34/558 (6.1%), including 9 major bleeding (1.6%) and 5 fatal events (0.9%); cerebral/peripheral thromboembolic events occurred in 15/558 (2.7%). At multivariable analysis (Figure1), NYHA ≥III (OR 0.50, 95%CI 0.29–0.87; p=0.014), and history of PVT (OR 0.38, 95%CI 0.18–0.83; p=0.012) were independently associated with a lower likelihood of success, whereas age, sex, atrial fibrillation, and side (left/right) of PVT were not.
Conclusion
In the present individual-patient pooled analysis of patients with acute MPVT, the slow/ultraslow low-dose thrombolytic regimen achieved a high success rate, as well as low in-hospital mortality, fatal bleeding (<1%), and thromboembolic events. This study is the largest analysis of the newly introduced thrombolytic regimen. Findings support the use of thrombolytic therapy as a compelling alternative to surgery—particularly in haemodynamically stable patients with low NYHA class and without a history of PVT—and the planning of randomised trials against contemporary surgical management.Figure 1