PMID- 30004572 OWN - NLM STAT- MEDLINE DCOM- 20180924 LR - 20230605 IS - 1469-493X (Electronic) IS - 1361-6137 (Linking) VI - 7 IP - 7 DP - 2018 Jul 13 TI - Antiplatelet and anticoagulant agents for primary prevention of thrombosis in individuals with antiphospholipid antibodies. PG - CD012534 LID - 10.1002/14651858.CD012534.pub2 [doi] LID - CD012534 AB - BACKGROUND: Antiphospholipid syndrome (APS) is an autoimmune disease characterised by the presence of antiphospholipid (aPL) antibodies that have prothrombotic activity. Antiphospholipid antibodies are associated with an increased risk of pregnancy complications (recurrent miscarriage, premature birth, intrauterine growth retardation) and thrombotic events (both arterial and venous). The most common thrombotic events include brain ischaemia (stroke or transient ischaemic attack) and deep vein thrombosis. To diagnose APS, the presence of aPL antibodies in two measurements and at least one thrombotic event or pregnancy complication are required. It is unclear if people with positive aPL antibodies but without any previous thrombotic events should receive primary antithrombotic prophylaxis. OBJECTIVES: To assess the effects of antiplatelet or anticoagulant agents versus placebo or no intervention or other intervention on the development of thrombosis in people with aPL antibodies who have not had a thrombotic event. We did not address obstetric outcomes in this review as these have been thoroughly addressed by other Cochrane Reviews. SEARCH METHODS: We searched the Cochrane Vascular Specialised Register (4 December 2017), the Cochrane Central Register of Controlled Trials (CENTRAL) (last search 29 November 2017), MEDLINE Ovid, Embase Ovid, CINAHL, and AMED (searched 4 December 2017), and trials registries (searched 29 November 2017). We also checked reference lists of included studies, systematic reviews, and practice guidelines, and contacted experts in the field. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared any antiplatelet or anticoagulant agents, or their combinations, at any dose and mode of delivery with placebo, no intervention, or other intervention. We also included RCTs that compared antiplatelet or anticoagulant agents with each other or that compared two different doses of the same drug. We included studies performed in people of any age and with no history of thrombosis (as defined by APS Sapporo classification criteria or updated Sydney classification criteria), but with aPL antibodies confirmed on at last two separate measurements. The studies included both pregnant women who tested positive for aPL antibodies and had a history of recurrent obstetric complications, as well as non-pregnancy related cases with positive screening for antibodies, in accordance with the criteria mentioned above. DATA COLLECTION AND ANALYSIS: Pairs of authors independently selected studies for inclusion, extracted data, and assessed the risk of bias for the included studies and quality of evidence using GRADE. Any discrepancies were resolved through discussion or by consulting a third review author when necessary. In addition, one review author checked all the extracted numerical data. MAIN RESULTS: We included nine studies involving 1044 randomised participants. The studies took place in several countries and had different funding sources. No study was at low risk of bias in all domains. We classified all included studies as at unclear or high risk of bias in two or more domains. Seven included studies focused mainly on obstetric outcomes. One study included non-pregnancy-related cases, and one study included both pregnancy-related cases and other patients with positive results for aPL antibodies. The remaining studies concerned women with aPL antibodies and a history of pregnancy failure. Four studies compared anticoagulant with or without acetylsalicylic acid (ASA) versus ASA only and observed no clear difference in thrombosis risk (risk ratio (RR) 0.98, 95% confidence interval (CI) 0.25 to 3.77; 4 studies; 493 participants; low-quality evidence). No major bleeding was reported, but minor bleeding risk (nasal bleeding, menorrhagia) was higher in the anticoagulant with ASA group as compared with ASA alone in one study (RR 22.45, 95% CI 1.34 to 374.81; 1 study; 164 participants; low-quality evidence). In one study ASA was compared with placebo, and there were no clear differences in thrombosis (RR 5.21, 95% CI 0.63 to 42.97; 1 study; 98 participants; low-quality evidence) or minor bleeding risk between the groups (RR 3.13, 95% CI 0.34 to 29.01; 1 study; 98 participants; low-quality evidence), and no major bleeding was observed. Two studies compared ASA with low molecular weight heparin (LMWH) versus placebo or intravenous immunoglobulin (IVIG), and no thrombotic events were observed in any of the groups. Moreover, there were no clear differences in the risk of bleeding requiring transfusion (RR 9.0, 95% CI 0.49 to 164.76; 1 study; 180 participants; moderate-quality evidence) or postpartum bleeding (RR 1.30, 95% CI 0.60 to 2.81; 1 study; 180 participants; moderate-quality evidence) between the groups. Two studies compared ASA with high-dose LMWH versus ASA with low-dose LMWF or unfractionated heparin (UFH); no thrombotic events or major bleeding was reported. Mortality and quality of life data were not reported for any of the comparisons. AUTHORS' CONCLUSIONS: There is insufficient evidence to demonstrate benefit or harm of using anticoagulants with or without ASA versus ASA alone in people with aPL antibodies and a history of recurrent pregnancy loss and with no such history; ASA versus placebo in people with aPL antibodies; and ASA with LMWH versus placebo or IVIG, and ASA with high-dose LMWH versus ASA with low-dose LMWH or UFH, in women with aPL antibodies and a history of recurrent pregnancy loss, for the primary prevention of thrombotic events. In a mixed population of people with a history of previous pregnancy loss and without such a history treated with anticoagulant combined with ASA, the incidence of minor bleeding (nasal bleeding, menorrhagia) was increased when compared with ASA alone. Studies that are adequately powered and that focus mainly on thrombotic events are needed to draw any firm conclusions on the primary prevention of thrombotic events in people with antiphospholipid antibodies. FAU - Bala, Malgorzata M AU - Bala MM AD - Chair of Epidemiology and Preventive Medicine; Department of Hygiene and Dietetics; Systematic Reviews Unit - Polish Cochrane Branch, Jagiellonian University Medical College, Kopernika 7, Krakow, Poland, 31-034. FAU - Paszek, Elzbieta AU - Paszek E FAU - Lesniak, Wiktoria AU - Lesniak W FAU - Wloch-Kopec, Dorota AU - Wloch-Kopec D FAU - Jasinska, Katarzyna AU - Jasinska K FAU - Undas, Anetta AU - Undas A LA - eng GR - ETM/442/CSO_/Chief Scientist Office/United Kingdom PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Review PT - Systematic Review DEP - 20180713 PL - England TA - Cochrane Database Syst Rev JT - The Cochrane database of systematic reviews JID - 100909747 RN - 0 (Antibodies, Antiphospholipid) RN - 0 (Anticoagulants) RN - 0 (Platelet Aggregation Inhibitors) SB - IM UOF - doi: 10.1002/14651858.CD012534 MH - *Antibodies, Antiphospholipid MH - Anticoagulants/*therapeutic use MH - Antiphospholipid Syndrome/*complications MH - Humans MH - Platelet Aggregation Inhibitors/*therapeutic use MH - *Primary Prevention MH - Randomized Controlled Trials as Topic MH - Thrombosis/*prevention & control PMC - PMC6513409 COIS- MMB receives honoraria as freelancer from a systematic review company that also works for pharmaceutical companies (Kleijnen Systematic Reviews Ltd). I am not aware of any direct conflict of interest.
 EP: Abbott Vascular paid for her registration fee for the 20th International Congress of the Polish Cardiac Society.
 WL has no known conflicts of interest.
 DWK is an investigator in a clinical trial on drug-resistant epilepsy conducted by UCB Pharma.
 KJ has no known conflicts of interest.
 AU received honoraria for lectures relating to anticoagulant therapy in Poland and had travel expenses covered by Bayer, Boehringer Ingelheim, Pfizer, and Sanofi-Aventis. EDAT- 2018/07/14 06:00 MHDA- 2018/09/25 06:00 PMCR- 2019/07/13 CRDT- 2018/07/14 06:00 PHST- 2018/07/14 06:00 [pubmed] PHST- 2018/09/25 06:00 [medline] PHST- 2018/07/14 06:00 [entrez] PHST- 2019/07/13 00:00 [pmc-release] AID - CD012534.pub2 [pii] AID - 10.1002/14651858.CD012534.pub2 [doi] PST - epublish SO - Cochrane Database Syst Rev. 2018 Jul 13;7(7):CD012534. doi: 10.1002/14651858.CD012534.pub2.