Identification | Study design | Country | Relevant patients | Intervention vs control | Follow-up | Mean age (SD)/(IQR) years | Female (%) | Outcomes |
Cohen et al23 | RCT | UK | 116 adults, with thrombotic APS (venous), receiving standard-intensity warfarin≥3 months since the last event. Women, if fertile, with adequate contraception. | 57 switched to Rivaroxaban (oral, one time a day, 20 mg, or 15 mg if creatinine clearance ≤29 mL/min) and 59 remained on Warfarin (target INR 2.0–3.0). | 210 days. | Rivaroxaban—47 (17). Warfarin—50 (14). | Rivaroxaban—42 (74%). Warfarin—42 (71%). | Primary: percentage change in endogenous thrombin potential from randomisation to day 42. Secondary: occurrence of TE and bleeding events to day 210, thrombin generation, markers of in-vivo coagulation activation, adherence to treatment and quality of life. |
Goldhaber et al25* | Posthoc subgroup analysis | Worldwide | 151 adult patients (with symptomatic, proximal DVT or PE in RE-COVER/RE-COVER II trials and additionally treated with AC for 3–12 months or with dabigatran during RE-COVER/RE-COVER II trials in RE-MEDY). | 71 on Dabigatran (oral, two times a day, 150 mg) and 80 on Warfarin (INR range 2.0–3.0). | 6 months in RE-COVER/RE-COVER II trials and 6–36 months in RE-MEDY. | Dabigatran —47.8 (14.9). Warfarin— 47.4 (16.8). | Dabigatran—24 (33.8%). Warfarin—31 (38.7%). | Primary— efficacy: recurrent symptomatic and objectively verified venous thromboembolism or death associated with venous thromboembolism (or unexplained death in the placebo-control study). Secondary: major bleeding, clinically relevant non-major bleeding, all bleeding events. |
Martinelli et al29† | Prospective cohort | Italy | 28 patients, with thrombotic APS (venous). | 13 on Rivaroxaban (oral, two times a day, 15 mg for 21 days followed by 20 mg one time a day or 20 mg one time a day if switched from VKA) and 15 on VKA. | 21.9 months (mean). | Rivaroxaban —46.2 (16.4). Warfarin— 43.1 (15.8). | Rivaroxaban—4 (30.8 %). VKA—5 (33.3 %). | Primary: recurrence of thrombosis. Secondary: major bleeding and clinically relevant non-major bleeding. |
Pengo et al22 | RCT | Italy | 120 adults, with APS positive for all 3 aPL tests (triple positivity) and history of thrombosis (arterial, venous and/or biopsy proven microthrombosis). | 59 on rivaroxaban (oral, one time a day, 20 mg or 15 mg if creatinine clearance 30–50 mL/min) and 61 on warfarin (target INR 2.0–3–0). | 611 days. | Rivaroxaban— 46.5 (10.2). Warfarin— 46.1 (13.2). | Rivaroxaban—39 (66%). Warfarin—38 (62%). | Primary: TE events, major bleeding and vascular death. Secondary: DVT, PE, intracerebral thrombosis, retinal thrombosis, peripheric or mesenteric artery thrombosis, small vessels thrombosis, AMI, stroke/TIA, fatal bleeding, clinically overt bleeding, critical area bleeding, minor bleeding, compliance with treatment. |
Malec et al30 | Prospective cohort | Poland | 176 patients diagnosed with APS. | DOACs: 36 on rivaroxaban (one time a day, 20 mg), 42 on apixaban (two times a day, 5 mg) and 4 on dabigatran (two times a day, 150 mg). 94 on VKA (target INR 2.0–3.0). | 51 months (median). | DOACs— 44 (11). VKA—45 (13). | DOACs—69 (84%). VKA—77 (82%). | Primary: symptomatic TE events (venous or arterial), PE, SVT, stroke, TIA, MI. Secondary: major bleeding, clinically relevant non-major bleeding. |
Ordi-Ros et al24 | RCT | Spain | 190 adults, with thrombotic APS (venous or arterial) and a positive aPL testing on 2 occasions at least 3 months apart. | 95 on rivaroxaban (one time a day, 20 mg or 15 mg if creatinine clearance 30–49 mL/min/1.73 m2) and 95 on VKA (target INR 2.0–3.0 or 3.1–4.0 if history of recurrent thrombosis). | 36 months. | Rivaroxaban—47 (40–55). VKA—51 (38–63). | Rivaroxaban—61 (64.2%). VKA—60 (63.2%). | Primary: new thrombotic events, major bleeding. Secondary: time to thrombosis, type of thrombotic event, non-major bleeding, CV death, changes in level of selected biomarkers. |
Sato et al31 | Retrospective cohort | Japan | 54 patients, with APS. | 18 on DOACs (5 on rivaroxaban, 12 on edoxaban and 1 on apixaban) and 36 on warfarin. | 60 months (at most). | DOACs—47.7 (17.1). Warfarin—42.6 (13.4). | DOACs—15 (83.3%). Warfarin—30 (83.3%). | Primary: event-free survival for 5 years (recurrence of arterial/venous thrombosis and severe bleeding requiring hospitalisation and/or transfusion). |
*Considering only patients with APS.
†Authors only present age at index thrombosis.
AC, anticoagulation; AMI, acute myocardial infarction; aPL, antiphospholipid; APS, antiphospholipid syndrome; CV, cardiovascular; DOACs, direct oral anticoagulants; DVT, deep vein thrombosis; MI, myocardial infarction; PE, pulmonary embolism; RCT, randomised controlled trial; SVT, supraventricular tachycardia; TE, thromboembolism; TIA, transient ischaemic attack; VKA, vitamin K antagonists.