Association Between Dabigatran vs Warfarin and Risk of Osteoporotic Fractures Among Patients With Nonvalvular Atrial Fibrillation | Atrial Fibrillation | JAMA | JAMA Network
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1.
Sugiyama  T, Kugimiya  F, Kono  S, Kim  YT, Oda  H.  Warfarin use and fracture risk: an evidence-based mechanistic insight.  Osteoporos Int. 2015;26(3):1231-1232.PubMedGoogle ScholarCrossref
2.
Caraballo  PJ, Heit  JA, Atkinson  EJ,  et al.  Long-term use of oral anticoagulants and the risk of fracture.  Arch Intern Med. 1999;159(15):1750-1756.PubMedGoogle ScholarCrossref
3.
Gage  BF, Birman-Deych  E, Radford  MJ, Nilasena  DS, Binder  EF.  Risk of osteoporotic fracture in elderly patients taking warfarin: results from the National Registry of Atrial Fibrillation 2.  Arch Intern Med. 2006;166(2):241-246.PubMedGoogle ScholarCrossref
4.
Rejnmark  L, Vestergaard  P, Mosekilde  L.  Fracture risk in users of oral anticoagulants: a nationwide case-control study.  Int J Cardiol. 2007;118(3):338-344.PubMedGoogle ScholarCrossref
5.
Fusaro  M, Dalle Carbonare  L, Dusso  A,  et al.  Differential effects of dabigatran and warfarin on bone volume and structure in rats with normal renal function.  PLoS One. 2015;10(8):e0133847.PubMedGoogle ScholarCrossref
6.
Panula  J, Pihlajamäki  H, Mattila  VM,  et al.  Mortality and cause of death in hip fracture patients aged 65 or older: a population-based study.  BMC Musculoskelet Disord. 2011;12:105.PubMedGoogle ScholarCrossref
8.
Hospital Authority.  Hospital Authority Statistical Report 2014-2015. http://www.ha.org.hk/haho/ho/stat/HASR1415_2.pdf. Accessed September 8, 2016.
9.
Wong  AYS, Root  A, Douglas  IJ,  et al.  Cardiovascular outcomes associated with use of clarithromycin: population based study.  BMJ. 2016;352:h6926.PubMedGoogle ScholarCrossref
10.
Chan  EW, Lau  WC, Leung  WK,  et al.  Prevention of dabigatran-related gastrointestinal bleeding with gastroprotective agents: a population-based study.  Gastroenterology. 2015;149(3):586-595.e3.PubMedGoogle ScholarCrossref
11.
Wong  AY, Wong  IC, Chui  CS,  et al.  Association between acute neuropsychiatric events and Helicobacter pylori therapy containing clarithromycin.  JAMA Intern Med. 2016;176(6):828-834.PubMedGoogle ScholarCrossref
12.
Chan  EW, Lau  WC, Siu  CW,  et al.  Effect of suboptimal anticoagulation treatment with antiplatelet therapy and warfarin on clinical outcomes in patients with nonvalvular atrial fibrillation: a population-wide cohort study.  Heart Rhythm. 2016;13(8):1581-1588.PubMedGoogle ScholarCrossref
13.
Chui  CS, Chan  EW, Wong  AY, Root  A, Douglas  IJ, Wong  IC.  Association between oral fluoroquinolones and seizures: a self-controlled case series study.  Neurology. 2016;86(18):1708-1715.PubMedGoogle ScholarCrossref
14.
Man  KK, Chan  EW, Coghill  D,  et al.  Methylphenidate and the risk of trauma.  Pediatrics. 2015;135(1):40-48.PubMedGoogle ScholarCrossref
15.
Chui  CS, Man  KK, Cheng  CL,  et al.  An investigation of the potential association between retinal detachment and oral fluoroquinolones: a self-controlled case series study.  J Antimicrob Chemother. 2014;69(9):2563-2567.PubMedGoogle ScholarCrossref
16.
Man  KK, Ip  P, Hsia  Y,  et al.  ADHD drug prescribing trend is increasing among children and adolescents in Hong Kong [published online July 3, 2014].  J Atten Disord. doi:10.1177/1087054714536047Google Scholar
17.
Hippisley-Cox  J, Coupland  C.  Predicting risk of osteoporotic fracture in men and women in England and Wales: prospective derivation and validation of QFractureScores.  BMJ. 2009;339:b4229.PubMedGoogle ScholarCrossref
18.
Austin  PC.  Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples.  Stat Med. 2009;28(25):3083-3107.PubMedGoogle ScholarCrossref
19.
Austin  PC.  Some methods of propensity-score matching had superior performance to others: results of an empirical investigation and Monte Carlo simulations.  Biom J. 2009;51(1):171-184.PubMedGoogle ScholarCrossref
20.
Stuart  EA, Lee  BK, Leacy  FP.  Prognostic score-based balance measures can be a useful diagnostic for propensity score methods in comparative effectiveness research.  J Clin Epidemiol. 2013;66(8)(suppl):S84-S90.e81PubMedGoogle ScholarCrossref
21.
Pasternak  B, Svanström  H, Melbye  M, Hviid  A.  Association between oral fluoroquinolone use and retinal detachment.  JAMA. 2013;310(20):2184-2190.PubMedGoogle ScholarCrossref
22.
Gage  BF, Birman-Deych  E, Kerzner  R, Radford  MJ, Nilasena  DS, Rich  MW.  Incidence of intracranial hemorrhage in patients with atrial fibrillation who are prone to fall.  Am J Med. 2005;118(6):612-617.PubMedGoogle ScholarCrossref
23.
Stürmer  T, Rothman  KJ, Avorn  J, Glynn  RJ.  Treatment effects in the presence of unmeasured confounding: dealing with observations in the tails of the propensity score distribution—a simulation study.  Am J Epidemiol. 2010;172(7):843-854.PubMedGoogle ScholarCrossref
24.
Tufano  A, Coppola  A, Contaldi  P, Franchini  M, Minno  GD.  Oral anticoagulant drugs and the risk of osteoporosis: new anticoagulants better than old?  Semin Thromb Hemost. 2015;41(4):382-388.PubMedGoogle ScholarCrossref
25.
Szulc  P, Arlot  M, Chapuy  MC, Duboeuf  F, Meunier  PJ, Delmas  PD.  Serum undercarboxylated osteocalcin correlates with hip bone mineral density in elderly women.  J Bone Miner Res. 1994;9(10):1591-1595.PubMedGoogle ScholarCrossref
26.
Ivaska  KK, Gerdhem  P, Akesson  K, Garnero  P, Obrant  KJ.  Effect of fracture on bone turnover markers: a longitudinal study comparing marker levels before and after injury in 113 elderly women.  J Bone Miner Res. 2007;22(8):1155-1164.PubMedGoogle ScholarCrossref
27.
January  CT, Wann  LS, Alpert  JS,  et al; ACC/AHA Task Force Members.  2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society.  Circulation. 2014;130(23):e199-e267.PubMedGoogle ScholarCrossref
28.
Feskanich  D, Weber  P, Willett  WC, Rockett  H, Booth  SL, Colditz  GA.  Vitamin K intake and hip fractures in women: a prospective study.  Am J Clin Nutr. 1999;69(1):74-79.PubMedGoogle Scholar
29.
Pilon  D, Castilloux  AM, Dorais  M, LeLorier  J.  Oral anticoagulants and the risk of osteoporotic fractures among elderly.  Pharmacoepidemiol Drug Saf. 2004;13(5):289-294.PubMedGoogle ScholarCrossref
30.
Misra  D, Zhang  Y, Peloquin  C, Choi  HK, Kiel  DP, Neogi  T.  Incident long-term warfarin use and risk of osteoporotic fractures: propensity-score matched cohort of elders with new onset atrial fibrillation.  Osteoporos Int. 2014;25(6):1677-1684.PubMedGoogle ScholarCrossref
31.
Woo  C, Chang  LL, Ewing  SK, Bauer  DC; Osteoporotic Fractures in Men Study Group.  Single-point assessment of warfarin use and risk of osteoporosis in elderly men.  J Am Geriatr Soc. 2008;56(7):1171-1176.PubMedGoogle ScholarCrossref
32.
Jamal  SA, Browner  WS, Bauer  DC, Cummings  SR; Study of Osteoporotic Fractures Research Group.  Warfarin use and risk for osteoporosis in elderly women.  Ann Intern Med. 1998;128(10):829-832.PubMedGoogle ScholarCrossref
33.
Sato  Y, Honda  Y, Jun  I.  Long-term oral anticoagulation therapy and the risk of hip fracture in patients with previous hemispheric infarction and nonrheumatic atrial fibrillation.  Cerebrovasc Dis. 2010;29(1):73-78.PubMedGoogle ScholarCrossref
34.
Benzinger  P, Rapp  K, König  HH,  et al.  Risk of osteoporotic fractures following stroke in older persons.  Osteoporos Int. 2015;26(4):1341-1349.PubMedGoogle ScholarCrossref
35.
Leslie  WD, Lix  LM; Manitoba Bone Density Program.  Absolute fracture risk assessment using lumbar spine and femoral neck bone density measurements: derivation and validation of a hybrid system.  J Bone Miner Res. 2011;26(3):460-467.PubMedGoogle ScholarCrossref
36.
Henau  K, Van Eycken  E, Silversmit  G, Pukkala  E.  Regional variation in incidence for smoking and alcohol related cancers in Belgium.  Cancer Epidemiol. 2015;39(1):55-65.PubMedGoogle ScholarCrossref
37.
Ip  TP, Cheung  SK, Cheung  TC,  et al; OSHK Task Group for Formulation of 2013 OSHK Guideline for Clinical Management of Postmenopausal Osteoporosis in Hong Kong; Osteoporosis Society of Hong Kong.  The Osteoporosis Society of Hong Kong (OSHK): 2013 OSHK guideline for clinical management of postmenopausal osteoporosis in Hong Kong.  Hong Kong Med J. 2013;19(suppl 2):1-40.PubMedGoogle ScholarCrossref
Original Investigation
March 21, 2017

Association Between Dabigatran vs Warfarin and Risk of Osteoporotic Fractures Among Patients With Nonvalvular Atrial Fibrillation

Author Affiliations
  • 1Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
  • 2Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
  • 3Department of Pediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
  • 4University of Birmingham Institute of Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom
  • 5Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
  • 6Cardiology Division, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR, China
  • 7Osteoporosis Centre, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR, China
  • 8Research Department of Practice and Policy, UCL School of Pharmacy, London, United Kingdom
JAMA. 2017;317(11):1151-1158. doi:10.1001/jama.2017.1363
Key Points

Question  What is the risk of osteoporotic fracture associated with the use of dabigatran compared with warfarin among patients with nonvalvular atrial fibrillation (NVAF)?

Findings  In this population-based cohort study of 8152 patients, use of dabigatran was associated with a significantly lower risk of osteoporotic fracture compared with warfarin (incidence, 0.7 vs 1.1 per 100 person-years) during a mean follow-up of approximately 500 days.

Meaning  Among adults with NVAF receiving anticoagulation, the use of dabigatran compared with warfarin was associated with a lower risk of osteoporotic fracture; further studies may be warranted to assess this further.

Abstract

Importance  The risk of osteoporotic fracture with dabigatran use in patients with nonvalvular atrial fibrillation (NVAF) is unknown.

Objective  To investigate the risk of osteoporotic fracture with dabigatran vs warfarin in patients with NVAF.

Design, Setting, and Participants  Retrospective cohort study using a population-wide database managed by the Hong Kong Hospital Authority. Patients newly diagnosed with NVAF from 2010 through 2014 and prescribed dabigatran or warfarin were matched by propensity score at a 1:2 ratio with follow-up until July 31, 2016.

Exposures  Dabigatran or warfarin use during the study period.

Main Outcomes and Measures  Risk of osteoporotic hip fracture and vertebral fracture was compared between dabigatran and warfarin users using Poisson regression. The corresponding incidence rate ratio (IRR) and absolute risk difference (ARD) with 95% CIs were calculated.

Results  Among 51 496 patients newly diagnosed with NVAF, 8152 new users of dabigatran (n = 3268) and warfarin (n = 4884) were matched by propensity score (50% women; mean [SD] age, 74 [11] years). Osteoporotic fracture developed in 104 (1.3%) patients during follow-up (32 dabigatran users [1.0%]; 72 warfarin users [1.5%]). Results of Poisson regression analysis showed that dabigatran use was associated with a significantly lower risk of osteoporotic fracture compared with warfarin (0.7 vs 1.1 per 100 person-years; ARD per 100 person-years, −0.68 [95% CI, −0.38 to −0.86]; IRR, 0.38 [95% CI, 0.22 to 0.66]). The association with lower risk was statistically significant in patients with a history of falls, fractures, or both (dabigatran vs warfarin, 1.6 vs 3.6 per 100 person-years; ARD per 100 person-years, −3.15 [95% CI, −2.40 to −3.45]; IRR, 0.12 [95% CI, 0.04 to 0.33]), but not in those without a history (0.6 vs 0.7 per 100 person-years; ARD per 100 person-years, −0.04 [95% CI, 0.67 to −0.39]; IRR, 0.95 [95% CI, 0.45 to 1.96]) (P value for interaction, <.001).

Conclusions and Relevance  Among adults with NVAF receiving anticoagulation, the use of dabigatran compared with warfarin was associated with a lower risk of osteoporotic fracture. Additional study, perhaps including randomized clinical trials, may be warranted to further understand the relationship between use of dabigatran vs warfarin and risk of fracture.

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