Table 2.
DOACs versus VKAs in patients with nonvalvular atrial fibrillation and CKD
| Author | Type of trial | N | CrCl | Treatment arms | Age, years | Males, % | AntiPLT use, % | TTR for VKA | Median FU, years | Stroke/SE HR (95% CI) | Mortality HR (95% CI) | Major bleeding HR (95% CI) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Moderate CKD | ||||||||||||
| RE-LY investigators [58] | Post hoc RCT | 3,374 | 30–50 | Dabigatran 150 mg bid | 75±7 | 53 | 42 | – | 2.0 | 0.55 (0.34–0.89) | 1.03 (0.82–1.30) | 1.22 (0.95–1.58) |
| Dabigatran 110 mg bid | 0.78 (0.51–1.21) | 0.97 (0.77–1.24) | 1.02 (0.78–1.33) | |||||||||
| ARISTOTLE investigators [59] | Post hoc RCT | 3,017 | 25–50 | Apixaban 5/2.5 mg bid | 78±7 | 47 | 35 | – | 1.8 | 0.61 (0.39–0.94) | 0.78 (0.63–0.96) | 0.48 (0.37–0.64) |
| ROCKET AF investigators [60] | Post hoc RCT | 2,450 | 30–50 | Rivaroxaban 15 mg qd | – | – | – | – | 1.9 | 0.84 (0.57–1.23) | – | 0.98 (0.73–1.3) |
| J-ROCKET Investigators [61] | Post hoc RCT | 284 | 30–50 | Rivaroxaban10 mg qd | 78 (74–81) | 70 | 43 | – | 2.2 | 0.82 (0.25–2.69) | 1.04 (0.07–16.7) | 0.89 (0.36–2.18) |
| ENGAGE-AF TIMI 48 [62] | Post hoc RCT | 2,740 | 30–50 | Edoxaban 30 mg qd | 79 (75–83) | 46 | 29 | 67 | 2.8 | 0.87 (0.65–1.18) | 0.82 (0.69–0.97) | 0.76 (0.58–0.98) |
| Severe CKD | ||||||||||||
| Stanifer et al. [50] | Post hoc RCT | 269 | 25–30 | Apixaban 5/2.5 mg bid | 81 (76–85) | 40 | 39 | 55 | 1.8 (median) | 0.55 (0.20–1.51) | 1.02 (0.64–1.67) | 0.34 (0.14–0.80) |
| Ashley et al. [63] | Cohort | 1,514 | <30 | DOACs | – | – | – | – | – | 0.41 (0.20–0.82) | 0.75 (0.51–1.10) | 1 (0.29–3.45) |
| Welander et al. [64] | Cohort | 1,113 | <30 | DOACs | – | – | – | 67 | – | 1.01 (0.50–2.04) | 1.46 (1.11–1.91) | 0.61 (0.40–0.92) |
| Yao et al. [65] | Cohort | 917 | <30 | Apixaban | – | – | – | – | – | 0.83 (0.26–2.67) | 0.83 (0.45–1.54) | 1.03 (0.57–1.84) |
| Rivaroxaban | 0.25 (0.03–1.96) | 0.51 (0.16–1.68) | 0.81 (0.33–1.96) | |||||||||
| Dabigatran | – | 1.35 (0.37–4.94) | 0.62 (0.12–3.16) | |||||||||
| Weir et al. [66] | Cohort | 2,317 | <30 | Rivaroxaban | 80±8 | 40 | 51 | – | – | 0.93 (0.46–1.90) | 0.91 (0.65–1.28) | |
| Hsu et al. [67] | Cohort | 1,011 | <30 | Dabigatran | – | – | – | 40 | – | 0.36 (0.03–3.97) | – | 1.93 (0.31–11.9) |
| Rivaroxaban | 0.74 (0.13–4.33) | 1.79 (0.39–8.25) | ||||||||||
| Apixaban | – | 0.08 (0.01–1.55) | ||||||||||
| Edoxaban | 0.30 (0.04–2.47) | 0.34 (0.03–3.87) | ||||||||||
| Coleman et al. [68] | Cohort | 6,744 | <30 | Rivaroxaban | 72 (63–80) | 61 | 18 | – | 1.4 | 0.55 (0.27–1.10) | – | 0.68 (0.47–0.99) |
| 18 | ||||||||||||
| Hanni et al. [69] | Cohort | 861 | <25 | Apixaban 5/2.5 mg bid | 74±14 | 47 | 72 | – | 0.5 | 0% | 11.8% | 0.8% |
| Warfarin | 67±15 | 76 | 1.4% | 14.9% | 1.6% | |||||||
| Schafer et al. [70] | Cohort | 604 | <30 | Apixaban 5/2.5 mg bid | 74±12 | 50 | 61 | – | 0.7±0.3 | 0.7% | – | 1.5% |
| Warfarin | 71±14 | 0.8±0.3 | 0.3% | 8.4% | ||||||||
| Herndon et al. [71] | Cohort | 111 | <30 | Apixaban 5/2.5 mg bid | 71±8 | 100 | 53 | – | – | 2.0% | – | 7.0% |
| Warfarin | 72±8 | 0% | 14.0% | |||||||||
| Stanton et al. [72] | Matched cohort | 146 | <30 | Apixaban 5/2.5 mg bid | 79±12 | 40 | 64 | 68 | – | 7.5% | – | 9.6% |
| Warfarin | 79±14 | 49 | 7.5% | 17.8% | ||||||||
| End-stage kidney disease | ||||||||||||
| VALKYRIE investigators [43] | RCT | 132 | HD | Rivaroxaban 10 mg qd | 80 (74–84) | 67 | 33 | 48 | 1.8 (1–3.4) | 0.41 (0.25–0.68) | 65.2% | 0.39 (0.17–0.90) |
| Rivaroxaban 10 mg qd + vitamin K2 | 80 (73–83) | 41 | 0.34 (0.19–0.61) | 64.3% | 0.48 (0.22–1.08) | |||||||
| Warfarin | 80 (72–84) | 32 | 72.7% | |||||||||
| RENAL-AF investigators [44] | RCT | 154 | HD | Apixaban 5/2.5 mg bid | 69 (61–76) | 64 | 39 | 44 | 330 days | 3.0% | 26.0% | 1.20 (0.63–2.30) |
| Warfarin (reference) | 68 (61–73) | 47 | 340 days | 3.3% | 18.0% | |||||||
| AXADIA-AFNET 8 [45] | RCT | 97 | HD | Apixaban 2.5 mg bid Phenprocoumon | 75±8 | 70 | 34 | 51 | 429 days | 20.8% | 18.8 | 0.93 (0.53–1.65) |
| 506 days | 30.6% | 24.5% | ||||||||||
Warfarin is the reference arm for all studies, unless stated otherwise.
antiPLT, antiplatelet; BID, twice daily; CHA2DS2-VASc, congestive heart failure, hypertension, age ≥75 years (doubled), diabetes mellitus, stroke (doubled), vascular disease, age 65–74 years and sex category (female); C.I., confidence interval; CKD, chronic kidney disease; CrCl, creatinine clearance (in mL/min); DOAC, direct oral anticoagulant; FU, follow-up; HD, hemodialysis; HR, hazard ratio; ICH, intracranial hemorrhage; N, total number of patients; QD, once daily: RCT, randomized controlled trials; Retro, retrospective; SD, standard deviation; SE, systemic embolism, TTR, time in therapeutic range; VKA, vitamin K antagonist.