direct oral anticoagulant (DAO)

systematic review meta-analysis network meta-analysis

Select acute coronary syndromeatrial fibrillationcardiovascular preventionheart failurethrombosis preventionvenous thrombosis elective major knee surgeryAll type of patientuncoded clinical condition ***elective hip replacementmedical patientsorthopaedic surgerypatients with cancersecondary prevention       direct anti-Xadirect factor Xa inhibitorsdirect oral anticoagulantExtended-duration prophylaxisidraparinuxNOACoral direct thrombin inhibitororal factor Xa inhibitororal factor Xa inhibitorssynthetic oligosaccharidesynthetic pentasaccharide rosuvastatinapixabanaspirinbetrixaban clopidogreldabigatranedoxabanidraparinuxotamixabanrivaroxabanximelagatran vs warfarinvs discontinuationvs placebovs placebo and controlvs placebo or controlvs anticoagulantvs antiplateletvs antiplatelet drugsvs heparin/VKAvs Low molecular weight heparinvs UFH       DOAC without heparinheparin - DOAC

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Group by Group by... nothing pathology treatment patient comparator classe classe comparator mechanism clinical condition MA  in first nothing pathology treatment patient comparator classe classe comparator mechanism clinical condition  in second nothing pathology treatment patient comparator classe classe comparator mechanism clinical condition  in third	Description Synopsis Comparison Treatments Patients Characteristics Method Risk of bias References None Tools Indexation					Results Global trial result Main results All results All result tag NCT results	Major bleeding (118)All cause death (105)Coronary event (57)major or clinically relevant non-major bleeding (57)total VTE and all-cause mortality (56)proximal DVT (55)major VTE (fatal and non fatal DVT,PE) (48)distal DVT (47)stroke (fatal and non fatal) (45)ischemic stroke (43)thrombo-embolic event (cerebral or systemic) (41)Haemmorhagic stroke (39)non-fatal pulmonary embolism (39)Fatal stroke (38)systemic thrombo-embolic complication (37)Symptomatic deep-vein thrombosis (37)Cardiovascular death (35)asymptomatic DVT (29)TE event or ischemic stroke or systemic embolism (26)Deep vein thrombosis (21)Symptomatic venous thromboembolism (DVT, PE) (21)Fatal bleeding (19)Gastrointestinal major bleeding (19)myocardial infarction (fatal and non fatal) (18)Lifethreatening major bleeding (15)VTE (15)Non fatal stroke (12)recurrent VTE during treatment (11)Non-lifethreatening major bleeding (10)Bleeding (10)cardiovascular events (8)any bleedings (7)Death related to venous thromboembolism (7)symptomatic pulmonary embolism (6)fatal pulmonary embolism (6)hypertransaminasemia (4)cardiac event (fatal and non fatal ) (3)Venous thromboembolism or death (3)Venous thromboembolism (3)recurrent VTE (3)stent thrombosis (2)major or minor bleeding (2)proximal deep-vein thrombosis (2)Symptomatic pulmonary embolism (1)pulmonary embolism (symptomatic and asymptomatic) (1)Recurrent thromboembolic event (1)Long term death (1)Recurrent DVT/DVT extension (symptomatic) (1)net benefit (1) Options Numeric bar chart forest plot medians
Trial	Studied trt	Control trt	patients	tags	ROB	Trial result	Major bleeding	All cause death
acute coronary syndrome
apixaban
APPRAISE-1 (10mg od), 2009      NCT	apixaban	placebo			Low risk of bias	negative
APPRAISE-1 (2.5 mg bid), 2009      NCT	apixaban	placebo			Low risk of bias	negative
APPRAISE 2, 2011      NCT	apixaban	placebo			Low risk of bias	negative
dabigatran
REDEEM, 2009    NCT	dabigatran	placebo			Low risk of bias	negative
otamixaban
SEPIA-ACS1 TIMI 42, 2009    NCT	otamixaban	unfractionated heparin			Low risk of bias	suggesting
rivaroxaban
ATLAS ACS-TIMI 46 (2.5mg), 2009      NCT	rivaroxaban 2.5mg	placebo			Low risk of bias	negative
ATLAS ACS 2 - TIMI 51 (2.5mg), 2011      NCT	rivaroxaban 2.5mg	placebo			Low risk of bias	suggesting
ATLAS ACS-TIMI 46 (5mg), 2009      NCT	rivaroxaban 5mg	placebo			Low risk of bias	negative
ATLAS ACS 2 - TIMI 51 (5mg), 2011      NCT	rivaroxaban 5mg	placebo				suggesting
ximelagatran
ESTEEM, 2003	ximelagatran	placebo			Exploratory	-
atrial fibrillation
apixaban
ARISTOTLE, 2011        NCT	apixaban	warfarin standard dose			Low risk of bias	conclusive
phase 2 apixaban    NCT	apixaban	warfarin standard dose			Exploratory	-
dabigatran
phase 2 dabigatran    NCT	dabigatran	warfarin standard dose			Exploratory	-
RE-LY (110mg), 2009      NCT	dabigatran 110mg	warfarin standard dose			Risk of bias	suggesting
PETRO (150mg), 2007	dabigatran 150mg	warfarin standard dose			Exploratory	-
RE-LY (150mg), 2009      NCT	dabigatran 150mg	warfarin standard dose			Risk of bias	suggesting
edoxaban
Weitz (edoxaban phase 2)    NCT	edoxaban	warfarin standard dose			Exploratory	-
phase 2 edoxaban    NCT	edoxaban	warfarin standard dose			Exploratory	-
ENGAGE-AF TIMI 48 High dose, 2013    NCT	edoxaban high dose	warfarin standard dose			Low risk of bias	suggesting
idraparinux
AMADEUS, 2008      NCT	idraparinux	warfarin standard dose			Risk of bias	negative
rivaroxaban
ROCKET-AF, 2010        NCT	rivaroxaban	warfarin standard dose			Low risk of bias	suggesting
ximelagatran
SPORTIF III, 2003	ximelagatran	warfarin standard dose			Risk of bias	suggesting
SPORTIF V, 2005	ximelagatran	warfarin standard dose			Low risk of bias	suggesting
SPORTIF II (ximelagatran vs warfarin standard dose), 2002	ximelagatran	warfarin standard dose			Risk of bias	-
cardiovascular prevention
rivaroxaban
COMPASS (rivaroxaban alone), 2017    NCT	rivaroxaban	aspirin	secondary prevention			-
COMPASS (rivaroxaban + aspirin), 2017      NCT	rivaroxaban + aspirin	aspirin	secondary prevention		Low risk of bias	-
heart failure
rivaroxaban
COMMANDER HF, 2018      NCT	rivaroxaban	placebo				negative
thrombosis prevention
apixaban
ADOPT, 2011      NCT	apixaban	enoxaparin	medical patients		Low risk of bias	suggesting
ADVANCE 3, 2010    NCT	apixaban	enoxaparin	hip surgery		Low risk of bias	suggesting
ADVANCE 2, 2010      NCT	apixaban	enoxaparin (europe regimen)	knee surgery		Low risk of bias	suggesting
APROPOS 2.5mg, 2007    NCT	apixaban	enoxaparin (US regimen)	knee surgery		Low risk of bias	negative
ADVANCE-1, 2008      NCT	apixaban	enoxaparin (US regimen)	knee surgery		Low risk of bias	suggesting
betrixaban
APEX, 2016    NCT	betrixaban	enoxaparin	medical patients		Low risk of bias	suggesting
dabigatran
RE-NOVATE (150mg), 2007      NCT	dabigatran 150mg	enoxaparin	hip surgery		Low risk of bias	negative
RE-NOVATE 2    NCT	dabigatran 220mg	enoxaparin	hip surgery		Low risk of bias	negative
RE-NOVATE (220mg), 2007      NCT	dabigatran 220mg	enoxaparin	hip surgery		Low risk of bias	negative
RE-MODEL (150mg), 2007	dabigatran 150mg	enoxaparin (europe regimen)	knee surgery		Low risk of bias	negative
RE-MODEL (220mg), 2007	dabigatran 220mg	enoxaparin (europe regimen)	knee surgery		Low risk of bias	negative
RE-MOBILIZE (150mg), 2008	dabigatran 150mg	enoxaparin (US regimen)	knee surgery		Low risk of bias	negative
RE-MOBILIZE (220mg), 2008	dabigatran 220mg	enoxaparin (US regimen)	knee surgery		Low risk of bias	negative
edoxaban
STARS J-V    NCT	edoxaban	enoxaparin (short duration)	hip surgery		Low risk of bias	suggesting
rivaroxaban
MARINER, 2018        NCT	rivaroxaban	placebo	medical patients		Low risk of bias	suggesting
RECORD 1, 2008      NCT	rivaroxaban	enoxaparin	hip surgery		Low risk of bias	suggesting
RECORD 3, 2008    NCT	rivaroxaban	enoxaparin (europe regimen)	knee surgery		Low risk of bias	suggesting
ODIXa-HIP 10mg, 2006	rivaroxaban	enoxaparin (short duration)	hip surgery		Low risk of bias	suggesting
RECORD 2, 2008    NCT	rivaroxaban (long duration)	enoxaparin (short duration)	hip surgery		Low risk of bias	suggesting
ODIXa-KNEE, 2005	rivaroxaban	enoxaparin (US regimen)	knee surgery		Low risk of bias	negative
RECORD 4, 2009    NCT	rivaroxaban	enoxaparin (US regimen)	knee surgery		Low risk of bias	suggesting
venous thrombosis
apixaban
AMPLIFY-EXT 2.5mg, 2012      NCT	apixaban 2.5mg	discontinuation			Low risk of bias	suggesting
AMPLIFY-EXT 5mg, 2012      NCT	apixaban 5mg	discontinuation			Low risk of bias	suggesting
Botticelli DVT, 2008      NCT	apixaban (without LMWH)	LMWH/VKA			Exploratory	-
AMPLIFY, 2013      NCT	apixaban (without LMWH)	LMWH/VKA		DOAC without heparin	Low risk of bias	suggesting
dabigatran
RE-MEDY, 2011      NCT	dabigatran	warfarin			Low risk of bias	suggesting
RE-SONATE, 2011    NCT	dabigatran	discontinuation			Low risk of bias	suggesting
RE-COVER II, 2011    NCT	heparin/dabigatran	heparin/VKA		heparin - DOAC	Low risk of bias	suggesting
RE-COVER, 2009      NCT	heparin/dabigatran	heparin/VKA		heparin - DOAC	Low risk of bias	suggesting
edoxaban
Hokusai-VTE Cancer, 2017      NCT	edoxaban	dalteparin	patients with cancer		Risk of bias	negative
Edoxaban Hokusai VTE, 2013      NCT	heparin/edoxaban	heparin/VKA		heparin - DOAC	Low risk of bias	suggesting
idraparinux
Van Gogh (subgroup), 2011	idraparinux	standard treatment	patients with cancer		Exploratory	negative
rivaroxaban
SELECT D, 2018	rivaroxaban	dalteparin	patients with cancer		Risk of bias	suggesting
EINSTEIN-extension, 2009    NCT	rivaroxaban	discontinuation			Low risk of bias	suggesting
EINSTEIN (subgroup), 2014	rivaroxaban	enoxaparin	patients with cancer			suggesting
Einstein-DVT Evaluation, 2010    NCT	rivaroxaban (without LMWH)	LMWH/VKA		DOAC without heparin	Low risk of bias	suggesting
Einstein-DVT Dose-Ranging Study, 2008	rivaroxaban (without LMWH)	LMWH/VKA				-
Einstein-PE Evaluation, 2012      NCT	rivaroxaban (without LMWH)	LMWH/VKA			Risk of bias	-
rosuvastatin
VanGogh extension, 2007      NCT	idraparinux	discontinuation				suggesting
ximelagatran
THRIVE III, 2003	ximelagatran	discontinuation			Low risk of bias	suggesting
Schulman (subgroup), 2003	ximelagatran	placebo	patients with cancer			-
THRIVE I, 2003	ximelagatran (without LMWH)	LMWH/VKA				-