Table 1.
Baseline characteristics and results of included trials.
| Study (patients) | Study design | Source of participant | Study Period | Intervention | Conventional treatment | Major GI bleeding, n/N NOAC vs n/N conventional treatment group |
| Atrial Fibrillation (11 studies) | ||||||
| Granger2011 | Double blind randomized | North America, South America, Europe, Asian Pacific | 2006–2010 | Apixaban (2.5 mg twice) | Warfarin | 150/9120 vs 119/9081 |
| Giugliano2013 | Double blind randomized | North America, South America, Europe, Asian Pacific | 2008–2010 | Edoxaban (60 mg, 30mg) | Warfarin | 361/14069 vs 190/7036 |
| Hori2013 | Double blind randomized | Asia | 2007–2010 | Rivaroxaban (15mg) | Warfarin | 8/639 vs 15/639 |
| Connolly2009 | Open-label randomized | North America, South America, Europe, Asian Pacific | 2005–2007 | Dabigatran (150 mg, 110mg) | Warfarin | 315/1291 vs 120/6022 |
| Patel 2011 | Double blind randomized | North America, South America, Europe, Asian Pacific | 2006–2009 | Rivaroxaban (20mg) | Warfarin | 224/7131 vs 154/7133 |
| Connolly2011 | Double blind randomized | North America, South America, Europe, Asian Pacific, South Africa | 2007–2009 | Apixaban (2.5 mg twice) | Aspirin (81–324mg) | 12/2808 vs 14/2791 |
| Chung 2011 | Double blind randomized | Asian countries (Taiwan, South Korea, Hong Kong and Singapore) | 2007–2008 | Edoxaban (60 mg, 30mg) | Warfarin | 0/159 vs 1/75 |
| Ogawa 2011 | Double blind randomized | Japan | Apixaban (2.5 mg twice,5 mg twice) | Warfarin | 0/75 vs 2/143 | |
| Abraham 2017 | Retrospective, propensity matched cohort study. | US, Optum Data Warehouse | 2010–2015 | Apixaban Dabigatran Rivaroxaban | None | 33/6542 222/15787 215/15787 |
| Abraham 2015 | Retrospective, propensity matched cohort study. | US, Optum Data Warehouse | 2010–2013 | Dabigatran Rivaroxaban | Warfarin | 18/7749 vs 22/7749 15/5166 vs 16/5166 |
| Graham 2016 | Retrospective, propensity matched cohort study. | US, fee-for-service Medicare | 2011–2014 | Dabigatran, 150 mg, twice daily; Rivaroxaban, 20 mg, once daily. | None | 362/52 240 656/66 651 |
| Yao 2016 | Retrospective, propensity matched cohort study. | US insurance database | 2010–2015 | Apixaban Dabigatran Rivaroxaban | Warfarin | 14/7695 vs 23/7695 28/14307 vs 28/14307 53/16175 vs 40/16175 |
| Venous thromboembolism or Pulmonary embolism (11 studies) | ||||||
| Bauersachs 2010 | Double blind randomized | 2007–2009 | Rivaroxaban (20mg) | Placebo | 3/598 vs 0/590 | |
| Buller 2012 | Open-label, randomized | 2007–2011 | Rivaroxaban (15 mg twice daily for 3 weeks, followed by 20 mg once daily | Enoxaparin | 1/2420 vs 2/2413 | |
| Yamada 2015 | Double blind randomized | Japan | 2012–2013 | Rivaroxaban (15 or 10 mg twice) | warfarin | 0/77 vs 0/19 |
| Agnelli 2013 (acute VTE) | Double blind randomized | North America, South America, Europe, Asian Pacific | 2008–2012 | Apixaban (5 mg twice) | Enoxaparin (1 mg/kilogram of body weight, 12 h) | 8/2676 vs 19/2689 |
| Agnelli 2013Ext | Double blind randomized | North America, South America, Europe, Asian Pacific | 2008–2011 | Apixaban (2.5 mg, 5mg) | Placebo | 1/1635 vs 1/829 |
| Nakamura 2015 | Double blind randomized | Japan | NA | Apixaban (10 mg twice) | Warfarin | 0/40 vs 0/40 |
| Buller 2013 | Double blind randomized | Europe | 2010–2012 | Edoxaban (60mg) | Warfarin | 27/4118 vs 18/4122 |
| Schulman 2009 | Double blind randomized | Europe, North America | 2006–2008 | Dabigatran (150mg) | Warfarin | 53/1274 vs 35/1265 |
| Schulman 2014 | Double blind randomized | Europe, North America | 2008–2010 | Dabigatran (150 mg twice) | Warfarin | 48/1279 vs 33/1289 |
| Schulman 2013 (RE-MEDY) | Double blind randomized | North America, South America, Europe, Asian Pacific | 2006–2010 | Dabigatran (150 mg twice) | Warfarin | 5/1430 vs 8/1426 |
| Schulman 2013 (RE-SONATE) | Double blind randomized | North America, South America, Europe, Asian Pacific | 2007–2010 | Dabigatran (150 mg twice) | Placebo | 2/681 vs 0/662 |
| Post-surgical prophylaxis of venous thromboembolism (11 studies) | ||||||
| Lassen 2009 | Double blind randomized | Europe | NA | Apixaban (2.5 mg twice) | Enoxaparin (30mg) | 1/1596 vs 6/1588 |
| Lassen 2010K | Double blind randomized | Europe | 2007–2008 | Apixaban (2.5 mg twice) | Enoxaparin (40mg) | 2/1501 vs 2/1508 |
| Lassen 2010H | Double blind randomized | Europe | 2007–2009 | Apixaban (2.5 mg twice) | Enoxaparin (40mg) | 4/2673 vs 0/2659 |
| Fuji 2014K | Double blind randomized | Japan | 2009 | Edoxaban (30mg) | Enoxaparin (2000IU) | 1/354 vs 0/349 |
| Fuji 2015 | Double blind randomized | Japan | 2009–2010 | Edoxaban (30mg) | Enoxaparin (2000IU) | 0/303 vs 2/301 |
| Fuji 2014H | Double blind randomized | Japan | 2008–2009 | Edoxaban (30mg) | Enoxaparin (2000IU) | 1/59 vs 0/29 |
| Eriksson 2007 | Double blind randomized | Europe | 2004–2006 | Dabigatran (150 mg or 220mg) | Enoxaparin | 1/2309 vs 0/1154 |
| Eriksson 2008 | Double blind randomized | Europe | 2006–2007 | Rivaroxaban (10mg) | Enoxaparin (40mg) | 2/2209 vs 1/2224 |
| Kakkar 2008 | Double blind randomized | Europe | 2006–2007 | Rivaroxaban (10mg) | Enoxaparin (40mg) | 1/1228 vs 0/1229 |
| Turpie 2009 | Double blind randomized | North America, Europe | 2006–2007 | Rivaroxaban (10mg) | Enoxaparin (30mg) | 1/1526 vs 0/1508 |
| Lassen 2008 | Double blind randomized | Europe | 2006 | Rivaroxaban 10mg | Enoxaparin (40mg) | 7/12,20 vs 6/1,239 |
NA = non-available.