Table 3 Open in new tab Major bleeding...

Concurrent antiepileptic medication

Person-quarters with NOAC use

Number of bleeding events

Crude major bleeding incidence rate (95% CI) per 1000 person-years

Adjusted incidence rate (95% CI) per 1000 person-years^a

Adjusted incidence rate difference (95% CI) per 1000 person-years^a

Adjusted rate ratio (95% CI)^a

Carbamazepine

With

1530

56.04 (36.74–85.49)

55.65 (36.49–84.88)

6.47 (–17.06–30.01)

1.13 (0.74–1.73)

Without^b

730 193

8525

47.16 (46.07–48.28)

49.18 (47.74–50.65)

Gabapentin

With

6227

108

68.75 (55.06– 85.85)

69.74 (56.04–86.78)

12.76 (–2.53–28.05)

1.22 (0.98–1.52)

Without^b

725 496

8438

46.99 (45.90–48.10)

56.98 (55.32–58.69)

Lamotrigine

With

463

50.11 (20.03–125.31)

51.36 (21.24–124.22)

3.64 (–41.76–49.04)

1.08 (0.44–2.61)

Without^b

731 260

8540

47.18 (46.09–48.29)

47.72 (45.37–50.20)

Levetiracetam

With

10 592

340

131.3 (116.95–147.42)

132.96 (118.54–149.15)

79.88 (64.47–95.30)

2.5 (2.22–2.83)

Without^b

721 131

8206

45.95 (44.87–47.05)

53.08 (50.96–55.30)

Oxcarbazepine

With

2761

55.9 (40.80–76.58)

55.95 (40.89–76.55)

3.77 (–13.85–21.39)

1.07 (0.78–1.47)

Without^b

728 962

8508

47.15 (46.06–48.26)

52.18 (50.52–53.90)

Phenobarbital

With

5702

42.09 (32.61–54.34)

42.25 (32.74–54.52)

–5.55 (–16.37–5.27)

0.88 (0.68–1.14)

Without^b

726 021

8486

47.22 (46.13–48.34)

47.8 (46.52–49.11)

Phenytoin

With

5190

171

134.78 (115.20–157.68)

135.83 (116.23–158.72)

81.4 (60.14–102.66)

2.5 (2.13–2.93)

Without^b

726 533

8375

46.55 (45.47–47.66)

54.43 (52.35–56.59)

Pregabalin

With

4324

61.03 (46.67–79.80)

62.71 (48.27–81.49)

7.59 (–8.92–24.10)

1.14 (0.87–1.48)

Without^b

727 399

8479

47.1 (46.01–48.21)

55.12 (53.40–56.91)

Topiramate

With

1110

55.16 (33.08–91.97)

54.83 (33.02–91.04)

4.4 (–23.47–32.26)

1.09 (0.65–1.81)

Without^b

730 613

8531

47.17 (46.08–48.28)

50.43 (48.68–52.24)

Valproic acid

With

10 848

401

151.3 (136.30–167.96)

153.49 (138.40–170.23)

98.43 (82.37–114.49)

2.79 (2.49–3.12)

Without^b

720 875

8145

45.62 (44.54–46.72)

55.06 (52.77– 57.45)

Zonisamide

With

336

72.83 (32.63–162.56)

72.24 (32.58–160.19)

21.87 (–35.74–79.47)

1.43 (0.65–3.19)

Without^b

731 387

8540

47.17 (46.08–48.28)

50.38 (47.71–53.19)

Table 3

Open in new tab

Major bleeding risk among AF patients taking a non-vitamin K antagonist oral anticoagulant for atrial fibrillation with or without concurrent antiepileptic medications

Concurrent antiepileptic medication	Person-quarters with NOAC use	Number of bleeding events	Crude major bleeding incidence rate (95% CI) per 1000 person-years	Adjusted incidence rate (95% CI) per 1000 person-years^a	Adjusted incidence rate difference (95% CI) per 1000 person-years^a	Adjusted rate ratio (95% CI)^a
Carbamazepine
With	1530	21	56.04 (36.74–85.49)	55.65 (36.49–84.88)	6.47 (–17.06–30.01)	1.13 (0.74–1.73)
Without^b	730 193	8525	47.16 (46.07–48.28)	49.18 (47.74–50.65)	6.47 (–17.06–30.01)	1
Gabapentin
With	6227	108	68.75 (55.06– 85.85)	69.74 (56.04–86.78)	12.76 (–2.53–28.05)	1.22 (0.98–1.52)
Without^b	725 496	8438	46.99 (45.90–48.10)	56.98 (55.32–58.69)	12.76 (–2.53–28.05)	1
Lamotrigine
With	463	6	50.11 (20.03–125.31)	51.36 (21.24–124.22)	3.64 (–41.76–49.04)	1.08 (0.44–2.61)
Without^b	731 260	8540	47.18 (46.09–48.29)	47.72 (45.37–50.20)	3.64 (–41.76–49.04)	1
Levetiracetam
With	10 592	340	131.3 (116.95–147.42)	132.96 (118.54–149.15)	79.88 (64.47–95.30)	2.5 (2.22–2.83)
Without^b	721 131	8206	45.95 (44.87–47.05)	53.08 (50.96–55.30)	79.88 (64.47–95.30)	1
Oxcarbazepine
With	2761	38	55.9 (40.80–76.58)	55.95 (40.89–76.55)	3.77 (–13.85–21.39)	1.07 (0.78–1.47)
Without^b	728 962	8508	47.15 (46.06–48.26)	52.18 (50.52–53.90)	3.77 (–13.85–21.39)	1
Phenobarbital
With	5702	60	42.09 (32.61–54.34)	42.25 (32.74–54.52)	–5.55 (–16.37–5.27)	0.88 (0.68–1.14)
Without^b	726 021	8486	47.22 (46.13–48.34)	47.8 (46.52–49.11)	–5.55 (–16.37–5.27)	1
Phenytoin
With	5190	171	134.78 (115.20–157.68)	135.83 (116.23–158.72)	81.4 (60.14–102.66)	2.5 (2.13–2.93)
Without^b	726 533	8375	46.55 (45.47–47.66)	54.43 (52.35–56.59)	81.4 (60.14–102.66)	1
Pregabalin
With	4324	67	61.03 (46.67–79.80)	62.71 (48.27–81.49)	7.59 (–8.92–24.10)	1.14 (0.87–1.48)
Without^b	727 399	8479	47.1 (46.01–48.21)	55.12 (53.40–56.91)	7.59 (–8.92–24.10)	1
Topiramate
With	1110	15	55.16 (33.08–91.97)	54.83 (33.02–91.04)	4.4 (–23.47–32.26)	1.09 (0.65–1.81)
Without^b	730 613	8531	47.17 (46.08–48.28)	50.43 (48.68–52.24)	4.4 (–23.47–32.26)	1
Valproic acid
With	10 848	401	151.3 (136.30–167.96)	153.49 (138.40–170.23)	98.43 (82.37–114.49)	2.79 (2.49–3.12)
Without^b	720 875	8145	45.62 (44.54–46.72)	55.06 (52.77– 57.45)	98.43 (82.37–114.49)	1
Zonisamide
With	336	6	72.83 (32.63–162.56)	72.24 (32.58–160.19)	21.87 (–35.74–79.47)	1.43 (0.65–3.19)
Without^b	731 387	8540	47.17 (46.08–48.28)	50.38 (47.71–53.19)	21.87 (–35.74–79.47)	1

Concurrent antiepileptic medication	Person-quarters with NOAC use	Number of bleeding events	Crude major bleeding incidence rate (95% CI) per 1000 person-years	Adjusted incidence rate (95% CI) per 1000 person-years^a	Adjusted incidence rate difference (95% CI) per 1000 person-years^a	Adjusted rate ratio (95% CI)^a
Carbamazepine
With	1530	21	56.04 (36.74–85.49)	55.65 (36.49–84.88)	6.47 (–17.06–30.01)	1.13 (0.74–1.73)
Without^b	730 193	8525	47.16 (46.07–48.28)	49.18 (47.74–50.65)	6.47 (–17.06–30.01)	1
Gabapentin
With	6227	108	68.75 (55.06– 85.85)	69.74 (56.04–86.78)	12.76 (–2.53–28.05)	1.22 (0.98–1.52)
Without^b	725 496	8438	46.99 (45.90–48.10)	56.98 (55.32–58.69)	12.76 (–2.53–28.05)	1
Lamotrigine
With	463	6	50.11 (20.03–125.31)	51.36 (21.24–124.22)	3.64 (–41.76–49.04)	1.08 (0.44–2.61)
Without^b	731 260	8540	47.18 (46.09–48.29)	47.72 (45.37–50.20)	3.64 (–41.76–49.04)	1
Levetiracetam
With	10 592	340	131.3 (116.95–147.42)	132.96 (118.54–149.15)	79.88 (64.47–95.30)	2.5 (2.22–2.83)
Without^b	721 131	8206	45.95 (44.87–47.05)	53.08 (50.96–55.30)	79.88 (64.47–95.30)	1
Oxcarbazepine
With	2761	38	55.9 (40.80–76.58)	55.95 (40.89–76.55)	3.77 (–13.85–21.39)	1.07 (0.78–1.47)
Without^b	728 962	8508	47.15 (46.06–48.26)	52.18 (50.52–53.90)	3.77 (–13.85–21.39)	1
Phenobarbital
With	5702	60	42.09 (32.61–54.34)	42.25 (32.74–54.52)	–5.55 (–16.37–5.27)	0.88 (0.68–1.14)
Without^b	726 021	8486	47.22 (46.13–48.34)	47.8 (46.52–49.11)	–5.55 (–16.37–5.27)	1
Phenytoin
With	5190	171	134.78 (115.20–157.68)	135.83 (116.23–158.72)	81.4 (60.14–102.66)	2.5 (2.13–2.93)
Without^b	726 533	8375	46.55 (45.47–47.66)	54.43 (52.35–56.59)	81.4 (60.14–102.66)	1
Pregabalin
With	4324	67	61.03 (46.67–79.80)	62.71 (48.27–81.49)	7.59 (–8.92–24.10)	1.14 (0.87–1.48)
Without^b	727 399	8479	47.1 (46.01–48.21)	55.12 (53.40–56.91)	7.59 (–8.92–24.10)	1
Topiramate
With	1110	15	55.16 (33.08–91.97)	54.83 (33.02–91.04)	4.4 (–23.47–32.26)	1.09 (0.65–1.81)
Without^b	730 613	8531	47.17 (46.08–48.28)	50.43 (48.68–52.24)	4.4 (–23.47–32.26)	1
Valproic acid
With	10 848	401	151.3 (136.30–167.96)	153.49 (138.40–170.23)	98.43 (82.37–114.49)	2.79 (2.49–3.12)
Without^b	720 875	8145	45.62 (44.54–46.72)	55.06 (52.77– 57.45)	98.43 (82.37–114.49)	1
Zonisamide
With	336	6	72.83 (32.63–162.56)	72.24 (32.58–160.19)	21.87 (–35.74–79.47)	1.43 (0.65–3.19)
Without^b	731 387	8540	47.17 (46.08–48.28)	50.38 (47.71–53.19)	21.87 (–35.74–79.47)	1

Adjusted by inverse probability of treatment weighting using the propensity score (sex, age, medical utilization, chronic kidney disease stage, anaemia, myocardial infarction, congestive heart failure, peripheral vascular disease, cerebrovascular disease, dementia, chronic pulmonary disease, rheumatic disease, peptic ulcer disease, mild liver disease, diabetes, hemiplegia or paraplegia, moderate or severe liver disease, percutaneous coronary intervention, coronary artery bypass surgery, transient ischaemic attack, hypertension, aspirin, clopidogrel, ticagrelor, ticlopidine, warfarin, glucocorticoids, insulin, lipid-lowering agents, hypoglycaemic agents, antihypertensive, non-steroid anti-inflammatory drugs, proton pump inhibitors, residence, income level, and occupation).

Without indicates NOAC alone.

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