For patients with symptomatic left-sided mechanical prosthetic valve thrombosis (PVT), the optimal treatment strategy between urgent surgery and fibrinolytic therapy (FT) has been uncertain. The SAFE-PVT trial, the first randomised controlled trial (RCT) to directly compare these approaches, found that while surgery is associated with a higher risk of complications and death, FT often results in residual valve dysfunction.¹

The SAFE-PVT trial was a single-centre, open-label RCT with blinded outcome assessment conducted in India. The study enrolled 79 adult patients (mean age 36 years) with symptomatic left-sided PVT of recent onset (≤2 weeks). Most patients had a thrombosed mitral prosthesis (72.2%), and 43% were in New York Heart Association (NYHA) class III/IV at presentation.

Patients were randomised to either urgent surgery (valve replacement or thrombectomy; n=39) or FT with low-dose, slow-infusion tissue plasminogen activator (t-PA; n=40). The primary efficacy outcome was a complete clinical response, defined as discharge from hospital with fully restored valve function and no major complications. The primary safety outcome was a composite of in-hospital death, non-fatal stroke, non-fatal major bleed, or systemic embolism.

There was no significant difference in the primary efficacy outcome between the two groups. A complete clinical response was achieved in 71.8% of patients in the surgery arm compared to 67.5% in the FT arm (odds ratio [OR] 1.22; 95% confidence interval [CI] 0.46–3.19; P=0.689).

However, the primary composite safety outcome occurred significantly more often in the surgery group (28.2% vs. 7.5%; OR 5.14; 95% CI 1.28–20.5; P=0.021). This difference was primarily driven by a higher rate of in-hospital deaths in the surgery arm compared to the FT arm (18% vs. 2.5%, respectively; P=0.035).

While surgery restored valve function in all patients who underwent the procedure, 25% of patients in the FT group (10/40) had residual valve dysfunction at discharge.

The findings from SAFE-PVT challenge current guidelines, which often recommend surgery as a first-line therapy for left-sided PVT.² The trial investigators concluded, "In symptomatic left-sided PVT, urgent surgery is not more efficacious than FT. Surgery is associated with a higher risk of complications, including death, while FT is more often associated with residual valve dysfunction."¹ Although FT appears to be a safer initial option, the high rate of residual valve dysfunction remains a clinical concern, potentially predisposing patients to future adverse events. The authors suggest that the focus of future research should be on improving the quality of oral anticoagulation to prevent PVT from occurring.

This study was funded by the Indian Council of Medical Research.

References

1. Karthikeyan G, Rajashekar P, Devasenapathy N, et al. Urgent surgery vs fibrinolytic therapy for left-sided prosthetic valve thrombosis: a randomized trial. Eur Heart J. 2025;46(34):3373–3381. https://doi.org/10.1093/eurheartj/ehaf391

2. Vahanian A, Beyersdorf F, Praz F, et al. 2021 ESC/EACTS guidelines for the management of valvular heart disease. Eur Heart J. 2022;43:561–632. https://doi.org/10.1093/eurheartj/ehab395

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