Effort induced subclavian vein thrombosis, also known as Paget-Schroetter syndrome (PSS) can be treated non-operatively with direct oral anticoagulation (AC), with percutaneous catheter directed thrombolysis (CDT), first rib resection (FRR) or a combination of treatments. Currently, there is no consensus on the optimal management of PSS. Our objective was to summarize the current evidence for management of PSS with explicit attention to the clinical outcomes of different management strategies. Main questions we wanted to address were: if surgical management of PSS consisting of CDT followed by FRR is superior to non-operative management with AC; does the use of CDT improve the outcomes of non-operative treated patients and does the use of CDT improve the outcomes of surgical treated patients with PSS?

A systematic review and meta-analysis was conducted following the PRISMA 2020 guidelines. The Cochrane, Pubmed and Embase databases were searched for reports published between January 1990 and December 2021. Primary endpoints were: the proportions of symptomfree patients at last follow up per treatment modality. Secondary outcomes were: primary patency, recurrence of thrombosis or persistent occlusion and patency at last follow up. Meta-analyses of the primary endpoints were performed for pooled single arms of different treatment modalities, using a general linear mixed model, displaying proportions of symptomfree patients. Meta-analyses of the pooled primary outcomes of al reports comparing treatment modalities were performed using a random effects model, displaying Risk Ratio's (RR). The Chi-square test was used to asses statistical significant differences between the incidences of secondary outcomes provided by all reports.

60 reports were included (2653 patients). The overall quality was rated ''moderate''. Non-operative management was reported in 24 reports (465 patients). The reported proportions of symptom free patients at last follow up from single arm analyses were: AC 0.54 (n=180, 95% CI 0.17 - 0.88) and CDT+AC 0.71 (n=150, 95% CI 0.44 - 0.89). Five reports compared AC with CDT+AC (43 vs. 70 patients). Meta-analysis showed a RR of 1.05 (95% CI 0.86 - 1.28; P = 0.64) of being symptom free at last follow-up. Secondary endpoints when comparing AC with CDT+AC did not differ significantly. Surgical management was reported in 51 reports (2208 patients). The reported proportions of symptom free patients at last follow up from single arm analyses were: FRR+AC 0.80 (n=171, 95% CI 0.56 - 0.93) and CDT+FRR 0.96 (n= 1284, 95% CI 0.91 - 0.98). Ten reports compared FRR + AC with CDT+FRR (142 vs 255 patients). Meta-analysis showed a RR of 1.09 (95% CI 0.91 - 1.31; P= 0.35) of being symptom free at last follow-up. Secondary outcomes were superior for patients treated by CDT+FRR versus to FRR+AC. Four reports were eligible for meta-analysis comparing AC with CDT+FRR (59 vs. 615 patients). Meta-analysis showed a RR of 2.47 (95% CI 0.86 - 7.09; P= 0.09) of being symptom free at last follow-up in favor of CDT+FFR. Secondary endpoints were in favor of CDT+FRR. Seven reports were included for meta-analysis comparing CDT+AC and CDT+FRR (47 vs 64 patients). RR was 1.38 of being symptom free when receiving CDT+FRR compared to CDT+AC (95% CI 0.86 - 2.22; P=0.18). Secondary endpoints were in favor of CDT+FRR.

This article supports the current consensus that a pro-active management of PSS with CDT followed by FRR results in the most favorable functional outcome with only 4% of patients reporting persistent symptoms. Nevertheless good functional outcomes were observed in patients with non-operative management only. Young and active patients who are unwilling to alter their high functional demand are in our opinion best of with CDT followed by FRR. Objectively informing the patient and shared-decision-making are essential when treating patients with PSS. The current recommendations are based on low grade evidence and need to be supported or rejected by future prospective randomized trials.

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