Risk of venous and arterial thrombosis in non-surgical patients receiving systemic tranexamic acid: A systematic review and meta-analysis.

BACKGROUND: Antifibrinolytic agents such as tranexamic acid (TXA) are commonly used as adjunctive therapies to prevent and treat excessive bleeding. In non-surgical settings, TXA is known to reduce bleeding related mortality. However, impact of TXA use on thrombosis is uncertain. METHODS: We systematically searched the MEDLINE, EMBASE, and CENTRAL databases from January 1985 to August 2018. Studies with the following characteristics were included: (i) RCT design; (ii) compared systemic (oral or intravenous) TXA for prevention or treatment of bleeding for non-surgical indications and placebo or no TXA, and (iii) reported thrombotic events or mortality. A Mantel-Haenzel, random-effects model was used to calculate risk ratios, and risk of bias was assessed using the Cochrane risk of bias tool. RESULTS: Our search identified 22 studies representing 49,538 patients. Those receiving TXA had a significantly lower risk of death from any cause (RR = 0.92; 95% CI = 0.87-0.98; I2 = 0%). There was no significant increase in the risk of stroke (RR = 1.10; 95% CI = 0.68-1.78; I2 = 31%), myocardial infarction (RR = 0.88; 95% CI = 0.43-1.84; I2 = 46%), pulmonary embolism (RR = 0.97; 95% CI = 0.75-1.26; I2 = 0%), or deep vein thrombosis (RR = 0.99; 95% CI = 0.70-1.41; I2 = 0%) from use of TXA. The results were similar when restricted to studies at low risk of bias. CONCLUSIONS: In our systematic review and meta-analysis, the use of tranexamic acid reduced all-cause mortality without increased risk of venous or arterial thrombotic complications.