The risk of venous thromboembolism associated with the use of tranexamic acid and other drugs used to treat menorrhagia: a case-control study using the General Practice Research Database

Abstract

Objective: To assess whether use of tranexamic acid is associated with an increased risk of venous thromboembolism (VTE).

Design: Nested case-control study.

Setting: Database study using the General Practice Research Database for the years 1992-1998.

Population: Women aged 15-49 years with a diagnosis of menorrhagia.

Methods: Multivariate conditional logistic regression was used to estimate the risk for VTE associated with different drug treatments for menorrhagia, adjusting for confounders.

Main outcome measures: Adjusted odds ratios with 95% CI.

Results: A total of 134 cases of VTE and 552 matched controls were identified. Recent use of tranexamic acid was scarce, yielding an adjusted odds ratio for VTE of 3.20 (95% CI 0.65-15.78). The use of mefenamic acid (ORadj 5.54 [95% CI 2.13-14.40]) or norethisterone (ORadj 2.41 [95% CI 1.00-5.78]) was associated with an increased risk of VTE, as was a recent--in relation to menorrhagia--diagnosis of anaemia or a haemoglobin value <11.5 g/dl (ORadj 2.23 [95% CI 1.02-4.86]).

Conclusions: We found that tranexamic acid was associated with an increased risk of VTE, although the risk estimate did not reach statistical significance. Increased risks of VTE associated with other treatments for menorrhagia were observed. The increased risk of VTE observed with a diagnosis of anaemia--a proxy for more severe menorrhagia--suggests that menorrhagia could be a prothrombotic condition. The observed association between VTE, tranexamic acid and other treatments for menorrhagia may thus partly be explained by confounding by indication. The possibility that menorrhagia is itself a risk factor for VTE merits further investigation.