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Research

Rates of hemorrhage during warfarin therapy for atrial fibrillation

Tara Gomes, Muhammad M. Mamdani, Anne M. Holbrook, J. Michael Paterson, Chelsea Hellings and David N. Juurlink
CMAJ February 05, 2013 185 (2) E121-E127; DOI: https://doi.org/10.1503/cmaj.121218
Tara Gomes
The Leslie Dan Faculty of Pharmacy (Gomes, Mamdani) and the Department of Health Policy, Management, and Evaluation (Juurlink, Mamdani, Paterson), University of Toronto; the Institute for Clinical Evaluative Sciences (Juurlink, Paterson, Hellings, Mamdani); the Sunnybrook Research Institute (Juurlink); and the Keenan Research Centre of the Li Ka Shing Knowledge Institute (Mamdani), St. Michael’s Hospital, Toronto, Ont.; the Department of Family Medicine (Paterson) and Division of Clinical Pharmacology & Therapeutics (Holbrook), McMaster University; and the Centre for Evaluation of Medicines (Holbrook, Paterson), St. Joseph’s Healthcare, Hamilton, Ont.
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  • For correspondence: tara.gomes@ices.on.ca
Muhammad M. Mamdani
The Leslie Dan Faculty of Pharmacy (Gomes, Mamdani) and the Department of Health Policy, Management, and Evaluation (Juurlink, Mamdani, Paterson), University of Toronto; the Institute for Clinical Evaluative Sciences (Juurlink, Paterson, Hellings, Mamdani); the Sunnybrook Research Institute (Juurlink); and the Keenan Research Centre of the Li Ka Shing Knowledge Institute (Mamdani), St. Michael’s Hospital, Toronto, Ont.; the Department of Family Medicine (Paterson) and Division of Clinical Pharmacology & Therapeutics (Holbrook), McMaster University; and the Centre for Evaluation of Medicines (Holbrook, Paterson), St. Joseph’s Healthcare, Hamilton, Ont.
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Anne M. Holbrook
The Leslie Dan Faculty of Pharmacy (Gomes, Mamdani) and the Department of Health Policy, Management, and Evaluation (Juurlink, Mamdani, Paterson), University of Toronto; the Institute for Clinical Evaluative Sciences (Juurlink, Paterson, Hellings, Mamdani); the Sunnybrook Research Institute (Juurlink); and the Keenan Research Centre of the Li Ka Shing Knowledge Institute (Mamdani), St. Michael’s Hospital, Toronto, Ont.; the Department of Family Medicine (Paterson) and Division of Clinical Pharmacology & Therapeutics (Holbrook), McMaster University; and the Centre for Evaluation of Medicines (Holbrook, Paterson), St. Joseph’s Healthcare, Hamilton, Ont.
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J. Michael Paterson
The Leslie Dan Faculty of Pharmacy (Gomes, Mamdani) and the Department of Health Policy, Management, and Evaluation (Juurlink, Mamdani, Paterson), University of Toronto; the Institute for Clinical Evaluative Sciences (Juurlink, Paterson, Hellings, Mamdani); the Sunnybrook Research Institute (Juurlink); and the Keenan Research Centre of the Li Ka Shing Knowledge Institute (Mamdani), St. Michael’s Hospital, Toronto, Ont.; the Department of Family Medicine (Paterson) and Division of Clinical Pharmacology & Therapeutics (Holbrook), McMaster University; and the Centre for Evaluation of Medicines (Holbrook, Paterson), St. Joseph’s Healthcare, Hamilton, Ont.
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Chelsea Hellings
The Leslie Dan Faculty of Pharmacy (Gomes, Mamdani) and the Department of Health Policy, Management, and Evaluation (Juurlink, Mamdani, Paterson), University of Toronto; the Institute for Clinical Evaluative Sciences (Juurlink, Paterson, Hellings, Mamdani); the Sunnybrook Research Institute (Juurlink); and the Keenan Research Centre of the Li Ka Shing Knowledge Institute (Mamdani), St. Michael’s Hospital, Toronto, Ont.; the Department of Family Medicine (Paterson) and Division of Clinical Pharmacology & Therapeutics (Holbrook), McMaster University; and the Centre for Evaluation of Medicines (Holbrook, Paterson), St. Joseph’s Healthcare, Hamilton, Ont.
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David N. Juurlink
The Leslie Dan Faculty of Pharmacy (Gomes, Mamdani) and the Department of Health Policy, Management, and Evaluation (Juurlink, Mamdani, Paterson), University of Toronto; the Institute for Clinical Evaluative Sciences (Juurlink, Paterson, Hellings, Mamdani); the Sunnybrook Research Institute (Juurlink); and the Keenan Research Centre of the Li Ka Shing Knowledge Institute (Mamdani), St. Michael’s Hospital, Toronto, Ont.; the Department of Family Medicine (Paterson) and Division of Clinical Pharmacology & Therapeutics (Holbrook), McMaster University; and the Centre for Evaluation of Medicines (Holbrook, Paterson), St. Joseph’s Healthcare, Hamilton, Ont.
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    Figure 1:

    Incident rate of visits to hospital with hemorrhages in 30-day increments after the start of warfarin therapy among older patients (≥ 66 yr) with atrial fibrillation. Rates are stratified by CHADS2 score at the start of treatment.

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    Table 1:

    Baseline characteristics of people starting warfarin therapy after atrial fibrillation was diagnosed

    CharacteristicPatients, no. (%)*
    n = 125 195
    Age at start of study, yr, median (IQR)77 (72–82)
    Age category, yr
     66–7553 260 (42.5)
     76–8556 026 (44.8)
     ≥ 8615 909 (12.7)
    Male sex61 911 (49.5)
    Income quintile
     124 945 (19.9)
     227 033 (21.6)
     324 707 (19.7)
     423 401 (18.7)
     524 752 (19.8)
     Missing357 (0.3)
    Rural residence18 942 (15.1)
    Charlson comorbidity index
     036 616 (29.2)
     126 397 (21.1)
     ≥ 239 919 (31.9)
     No admission to hospital22 263 (17.8)
    Drugs prescribed in past 1 yr, no., median (IQR)8 (5–12)
    Previous admission to hospital for hemorrhage5 596 (4.5)
    Resident of long-term care facility6 411 (5.1)
    Comorbidity (past 3 yr)
     Renal disease1 876 (1.5)
     Liver disease3 873 (3.1)
     Alcoholism3 801 (3.0)
     Dementia11 831 (9.5)
    Medication use (past 120 d)
     Acetylsalicylic acid24 328 (19.4)
     Acetylsalicylic acid and clopidogrel557 (0.4)
     Acetylsalicylic acid and dipyridamole817 (0.7)
     Other nonsteroidal anti-inflammatory drugs20 671 (16.5)
     Clopidogrel4 151 (3.3)
     Ticlopidine1 092 (0.9)
    Time to starting warfarin therapy, d, median (IQR)7 (2–22)
     021 573 (17.2)
     1–741 278 (33.0)
     8–1421 090 (16.8)
     15–3016 976 (13.6)
     31–10024 278 (19.4)
    CHADS2 score (components)
     Congestive heart failure44 011 (35.2)
     Hypertension94 063 (75.1)
     Age > 75 yr78 408 (62.6)
     Diabetes30 437 (24.3)
     Previous stroke26 661 (21.3)
    CHADS2 score
     08 655 (6.9)
     130 108 (24.0)
     244 716 (35.7)
     329 713 (23.7)
     49 599 (7.7)
     51 860 (1.5)
     6544 (0.4)
    • Note: IQR = interquartile range.

    • ↵* Unless otherwise indicated.

    • View popup
    Table 2:

    Rates of hemorrhage by length of time since starting warfarin therapy

    CharacteristicHemorrhages during 5-yr follow-up, no. (%)*Rate of hemorrhage, % per person-year (95% CI)
    First 30 dRemainder of 5-yr follow-upOverall
    Overall, no.10 84011.8 (11.1–12.4)3.4 (3.4–3.5)3.8 (3.8–3.9)
    CHADS2 score
     0382 (3.5)7.2 (5.5–9.5)1.6 (1.4–1.7)1.8 (1.6–2.0)
     11 845 (17.0)7.3 (6.3–8.4)2.3 (2.2–2.4)2.5 (2.4–2.6)
     2–37 053 (65.1)13.3 (12.5–14.3)3.8 (3.7–3.9)4.3 (4.2–4.4)
     4–61 560 (14.4)16.7 (14.3–19.4)6.0 (5.7–6.3)6.7 (6.3–7.0)
    Type of hemorrhage
     Intracranial549 (5.1)0.4 (0.4–0.5)0.2 (0.2–0.2)0.2 (0.2–0.2)
     Upper gastrointestinal2 829 (26.1)4.0 (3.8–4.2)0.9 (0.8–0.9)1.0 (1.0–1.0)
     Lower gastrointestinal3 956 (36.5)4.6 (4.4–4.9)1.2 (1.2–1.3)1.4 (1.4–1.4)
     Other4 190 (38.7)4.7 (4.5–5.0)1.3 (1.3–1.3)1.5 (1.5–1.5)
    Age ≤ 75 yr, no.36849.2 (8.4–10.2)2.6 (2.5–2.7)2.9 (2.8–3.0)
    CHADS2 score
     0382 (10.4)7.2 (5.5–9.5)1.6 (1.4–1.7)1.8 (1.6–2.0)
     11 204 (32.7)6.8 (5.7–8.1)2.0 (1.9–2.2)2.3 (2.1–2.4)
     2–31 881 (51.1)12.1 (10.6–13.9)3.4 (3.3–3.6)3.9 (3.7–4.0)
     4–6217 (5.9)13.1 (8.2–20.7)5.5 (4.8–6.4)6.0 (5.3–6.9)
    Type of hemorrhage
     Intracranial194 (5.3)0.4 (0.3–0.4)0.1 (0.1–0.1)0.2 (0.1–0.2)
     Upper gastrointestinal1 055 (28.6)3.9 (3.5–4.3)0.7 (0.7–0.7)0.8 (0.8–0.9)
     Lower gastrointestinal1 268 (34.4)3.5 (3.2–3.9)0.9 (0.9–0.9)1.0 (1.0–1.0)
     Other1 406 (38.2)3.3 (3.0–3.7)1.0 (1.0–1.0)1.1 (1.1–1.1)
    Age > 75 yr, no.7 15613.7 (12.7–14.6)4.1 (4.0–4.2)4.6 (4.5–4.7)
    CHADS2 score
     00 (0.0)———
     1641 (9.0)8.5 (6.6–10.9)2.8 (2.6–3.1)3.1 (2.9–3.4)
     2–35 172 (72.3)13.8 (12.8–15.0)4.0 (3.9–4.1)4.5 (4.4–4.6)
     4–61 343 (18.8)17.3 (14.6–20.3)6.1 (5.7–6.4)6.8 (6.4–7.1)
    Type of hemorrhage
     Intracranial355 (5.0)0.5 (0.4–0.5)0.2 (0.2–0.2)0.2 (0.2–0.2)
     Upper gastrointestinal1 774 (24.8)4.1 (3.8–4.3)1.0 (1.0–1.0)1.1 (1.1–1.2)
     Lower gastrointestinal2 688 (37.6)5.5 (5.1–5.9)1.5 (1.5–1.6)1.7 (1.7–1.8)
     Other2 784 (38.9)5.7 (5.3–6.1)1.6 (1.5–1.6)1.8 (1.8–1.8)
    • Note: CI = confidence interval.

    • ↵* Unless otherwise indicated

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Rates of hemorrhage during warfarin therapy for atrial fibrillation
Tara Gomes, Muhammad M. Mamdani, Anne M. Holbrook, J. Michael Paterson, Chelsea Hellings, David N. Juurlink
CMAJ Feb 2013, 185 (2) E121-E127; DOI: 10.1503/cmaj.121218

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Rates of hemorrhage during warfarin therapy for atrial fibrillation
Tara Gomes, Muhammad M. Mamdani, Anne M. Holbrook, J. Michael Paterson, Chelsea Hellings, David N. Juurlink
CMAJ Feb 2013, 185 (2) E121-E127; DOI: 10.1503/cmaj.121218
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