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Recombinant tissue plasminogen activator as a modifier of treatment effect in prosthetic valve thrombosis: systematic review and meta-regression
Session:
Prémio Melhor Comunicação Oral
Speaker:
Emídio Mata
Congress:
CPC 2026
Topic:
D. Heart Failure
Theme:
11. Acute Heart Failure
Subtheme:
11.7 Acute Heart Failure - Other
Session Type:
Sessão de Prémios
FP Number:
---
Authors:
Emídio Mata; Bernardo Resende; Ana Marta Pinto; Margarida Castro; João Gameiro; Sílvia Ribeiro; Gonçalo Ferraz-Costa; Lino Gonçalves; António Lourenço
Abstract
<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:Aptos,sans-serif"><strong><span style="font-size:11.0pt">Background:</span></strong><span style="font-size:11.0pt"> Obstructive prosthetic valve thrombosis (PVT) is a rare but potentially fatal complication. Optimal first-line therapy remains debated. Historically, surgery has been favoured, but advances in low-dose, slow-infusion recombinant tissue plasminogen activator (rt-PA) protocols have improved outcomes with fibrinolysis.</span></span></span></p> <p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:Aptos,sans-serif"><strong><span style="font-size:11.0pt">Objective:</span></strong><span style="font-size:11.0pt"> To compare surgical and fibrinolytic approaches for PVT using meta-analysis and meta-regression, focusing on how rt-PA–based protocols may modify treatment effects.</span></span></span></p> <p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:Aptos,sans-serif"><strong><span style="font-size:11.0pt">Methods:</span></strong><span style="font-size:11.0pt"> A systematic search of five databases identified studies comparing fibrinolysis and surgery for PVT. Random-effects meta-analyses estimated pooled risk ratios (RRs) with 95% confidence intervals, and mixed-effects meta-regression assessed the influence of rt-PA use on in-hospital mortality, complete valve restoration (without death), and recurrence.</span></span></span></p> <p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:Aptos,sans-serif"><strong><span style="font-size:11.0pt">Results:</span></strong><span style="font-size:11.0pt"> Thirteen studies (12 observational, 1 RCT; 586 fibrinolysis, 714 surgery) from 1978–2023 were included. Streptokinase (SK) was the most common fibrinolytic agent, while urokinase (UK) and rt-PA were less frequent, with rt-PA use increasing in recent studies.</span></span></span></p> <p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:Aptos,sans-serif"><span style="font-size:11.0pt">Across all studies, fibrinolysis and surgery had similar in-hospital mortality (RR 0.62 [0.32–1.21] I²=57%), though fibrinolysis showed lower complete valve restoration (RR 2.02 [1.25–3.27] I²=70%). Restricting analyses to rt-PA–based regimens, fibrinolysis significantly reduced in-hospital mortality (RR 0.12, [0.04–0.40] I²=0%) without affecting valve restoration (RR 1.62 [0.64–4.13] I²=82%).</span></span></span></p> <p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:Aptos,sans-serif"><span style="font-size:11.0pt">Meta-regression showed that for cohorts with 0% rt-PA usage, the baseline RR for in-hospital mortality was 1.24 [0.68–2.26]. Each 10% increase in rt-PA usage reduced RR by 19% (0.81 [0.70–0.93], P = 0.003), with low–moderate residual heterogeneity (I² = 27.5%) and 67% of between-study variance explained. For complete valve restoration, the baseline RR at 0% rt-PA usage was 2.74 [1.41–5.34], favouring surgery. Each 10% rise in rt-PA usage corresponded to a nonsignificant 7% RR reduction (0.93 [0.84–1.04], P = 0.20), suggesting a trend toward improved valve restoration with fibrinolysis.</span></span></span></p> <p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:Aptos,sans-serif"><strong><span style="font-size:11.0pt">Discussion: </span></strong><span style="font-size:11.0pt">Despite historical preference for surgery, modern rt-PA-based fibrinolysis may be comparable and possibly superior for obstructive PVT, providing similar rates of valve restoration while significantly reducing in-hospital mortality. Meta-regression identifies rt-PA as a strong moderator of treatment effect, with greater usage linked to lower mortality.</span></span></span></p>
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