Elsevier

Autoimmunity Reviews

Volume 13, Issue 3, March 2014, Pages 281-291
Autoimmunity Reviews

Review
Efficacy of aspirin for the primary prevention of thrombosis in patients with antiphospholipid antibodies: An international and collaborative meta-analysis

https://doi.org/10.1016/j.autrev.2013.10.014Get rights and content

Abstract

We performed a meta-analysis to determine whether aspirin has a significant protective effect on risk of first thrombosis among patients with antiphospholipid antibodies (aPL +). Observational and interventional studies identified from the Medline, Embase and Cochrane databases were selected if they assessed the incidence of first thrombosis in aPL + patients treated with aspirin versus those without. Pooled effect estimates were obtained using a random-effects model. Of 1211 citation retrieved, 11 primary studies (10 observational and 1 interventional) met inclusion criteria, including a total of 1208 patients and 139 thrombotic events. The pooled odds ratio (OR) for the risk of first thrombosis in patients treated with aspirin (n = 601) was 0.50 (95%CI: 0.27 to 0.93) compared to those without aspirin (n = 607), with significant heterogeneity across studies (I2 = 46%, p = 0.05). Subgroup analysis showed a protective effect of aspirin against arterial (OR: 0.48 [95%CI: 0.28–0.82]) but not venous (OR: 0.58 [95% CI: 0.32–1.06]) thrombosis, as well as in retrospective (OR: 0.23 [0.13–0.42]) but not prospective studies (OR: 0.91 [0.52–1.59]). Subgroup analysis according to underlying disease revealed a significant protective effect of aspirin for asymptomatic aPL + individuals (OR: 0.50 [0.25–0.99]), for systemic lupus erythematosus (SLE) (OR: 0.55 [0.31–0.98]) and obstetrical antiphospholipid syndrome (APS) (OR: 0.25 [0.10–0.62]). This meta-analysis shows that the risk of first thrombotic event is significantly decreased by low dose aspirin among asymptomatic aPL individuals, patients with SLE or obstetrical APS. Importantly, no significant risk reduction was observed when considering only prospective studies or those with the best methodological quality.

Introduction

Antiphospholipid antibodies (aPL) are a heterogeneous family of autoantibodies directed against phospholipid and/or phospholipid-binding proteins, which include, among others, lupus anticoagulants (LA), anticardiolipin antibodies (aCL) and anti-β2GPI antibodies (anti-β2GPI) [1], [2]. aPL predispose to pregnancy morbidity and vascular thrombosis, which clinically define the antiphospholipid syndrome [3]. They can be detected in a variety of situations, including auto-immune diseases such as systemic lupus erythematosus (SLE), pre-surgical testing or blood donation in the general population, or during investigations for recurrent spontaneous abortion, fetal death or premature birth. They may also be detected during infections but in that case are mostly transient. The exact prevalence of aPL in the general population as well as in SLE patients is currently debated due to previous aPL assay standardization and threshold issues [4], [5], [6], [7], [8]. Based on a limited number of studies, the incidence of a first thrombotic event is estimated to range from 0 to 1 for 100 patient-years in asymptomatic aPL + individuals, from 2 to 4 for 100 patient-years in aPL + patients with SLE and up to 7 for 100 patient-years in those with obstetrical APS associated with SLE [9], [10], [11]. There is a general agreement on long term anticoagulation to prevent recurrences of thrombosis in patients with APS [12]. However, there is limited evidence regarding the adequate primary prevention of thrombosis in aPL carriers [13]. Aspirin has been shown effective for the primary prevention of arterial thrombotic events in high-risk individuals in the general population [14]. The use of low-dose aspirin has recently been advocated in aPL + patients at high-risk for thrombosis such as those with SLE or positive LA or persistently positive aCL at medium-high titers or in the presence of other thrombotic risk factors [9]. Additionally, low dose aspirin may also prevent venous thrombosis as it has been recently reported in the secondary prevention of venous thromboembolism in the general population [15]. Yet, the prescription of low dose aspirin to prevent the first thrombosis in aPL carriers remains very controversial because of the conflicting results among the previous studies [13]. We therefore conducted a systematic review of the literature and meta-analysis to assess the efficacy of low-dose aspirin for the primary prevention of thrombosis in aPL + patients.

Section snippets

Methods

This meta-analysis was performed in accordance with the recommendations of the Meta-analysis of Observational Studies in Epidemiology (MOOSE) group [16].

Literature search

Our literature search identified 1211 citations, of which 11 unique studies [17], [18], [19], [25], [27], [29], [34], [35], [36], [37] were included in this meta-analysis (Fig. 1). The reasons for the exclusion of some articles after a full text review [20], [25], [26], [28], [38], [39], [40], [41], [42], [43], [44], [45] are shown in Fig. 1.

Publication bias

Visual examination of the funnel plot (Appendix B) only revealed minor asymmetry and Egger's test (p = 0.38) did not show any statistical evidence for

Discussion

Our meta-analysis of 11 studies including 1208 aPL + patients and 139 thrombotic events revealed that aPL + patients treated with long term low-dose aspirin have a 50% risk reduction for the occurrence of a first thrombotic event than those who did not receive this treatment. Additionally, subgroup analysis according to the pathogenic backgrounds revealed that the risk reduction was significant among asymptomatic aPL + individuals as well as among aPL + patients with SLE or obstetrical APS.

Up to

Take-home messages

  • The use of low dose aspirin to prevent a first thrombosis in patients with antiphospholipid antibodies (aPL) remains controversial.

  • Our meta-analysis of 11 primary studies including a total of 1208 patients compared the occurrence of a first thrombotic event in aPL patients with versus without low-dose aspirin.

  • We observed a significant decrease in the risk of arterial but not venous thrombosis in aPL patients treated with low-dose aspirin.

  • The risk of first thrombotic event was significantly

Acknowledgments

None.

Competing interests

No author has any conflict of interest to disclose.

Contributions

Laurent ARNAUD, Alexis MATHIAN, Stephane ZUILY, Denis WAHL & Zahir AMOURA designed the research. Amelia RUFFATTI, Doruk ERKAN, Maria TEKTONIDOU, Ricard CERVERA, Ricardo FORASTIERO, Vittorio PENGO, Marc LAMBERT, Maria Angeles MARTINEZ-ZAMORA, Juan BALASCH, Laurent ARNAUD, Alexis MATHIAN, Stephane ZUILY, Denis WAHL & Zahir AMOURA performed the research. Laurent ARNAUD, Alexis MATHIAN, Stephane ZUILY, Denis

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  • Cited by (0)

    1

    Laurent Arnaud & Alexis Mathian contributed equally to this work.

    2

    Denis Wahl & Zahir Amoura contributed equally to this work.

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