Introduction: Since the management of free-floating thrombus (FFT), a critical clinical entity associated with an increased risk of stroke or transient ischemic attack (TIA), is controversial, we performed a systematic review of the efficacy of various medical interventions in the management of FFT and factors associated with FFT resolution and recurrence.

Methods: We included studies from PubMed and EMBASE that reported patients diagnosed with FFT-related stroke or TIA who received anticoagulation or antiplatelet therapy or a combination. The primary outcomes were stroke recurrence and thrombus resolution. Statistical significance was determined at p<0.05 using Fisher's exact test, the chi-square test, the Mann–Whitney test, or the Kruskal–Wallis test.

Results: Our review (61 studies) included 179 patients diagnosed with FFT with a median follow-up duration of 7 months. Resolution of the thrombus occurred in 117 (65%), while 20 (12.6%) experienced recurrence, predominantly manifesting as TIAs. The incidence of cardioembolism was greater in the patients with unresolved thrombi (7.7% (n=9), p=0.025). Patients who received combination therapy involving antiplatelet agents, anticoagulants, and statins showed a higher probability of clot resolution ([OR] 11.4; 95% [CI] 1.436-91.91; p=0.021) compared to those treated with anticoagulant or antiplatelet therapy alone ([OR] 1.201; 95% [CI] 0.601-2.40; p=0.604, [OR] 0.780; 95% [CI] 0.317-1.92; p=0.588), respectively. Notably, ulcerated plaques predicted recurrence ([OR] 8.2; 95% [CI] 1.02-66.07; p=0.048).

Conclusions: Combination medical therapy of antiplatelets, anticoagulants, and statins is superior to anticoagulant or antiplatelet therapy alone. Moreover, the identification of ulcerated plaques as a significant predictor of recurrence underscores the importance of targeted interventions in high-risk patients.