Jenny I Shen1, Maria E Montez-Rath2, Colin R Lenihan2, Mintu P Turakhia3, Tara I Chang4, Wolfgang C Winkelmayer5. 1. Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Palo Alto, CA; Division of Nephrology and Hypertension, Harbor-UCLA Medical Center, Torrance, CA. 2. Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Palo Alto, CA. 3. Division of Cardiovascular Medicine, Department of Medicine, Palo Alto, CA; Veterans Affairs Palo Alto Health Care System, Stanford University School of Medicine, Palo Alto, CA. 4. Section of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, TX. 5. Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Palo Alto, CA; Division of Cardiovascular Medicine, Department of Medicine, Palo Alto, CA. Electronic address: wolfgang.winkelmayer@bcm.edu.
Abstract
BACKGROUND: Although warfarin is indicated to prevent ischemic strokes in most patients with atrial fibrillation (AF), evidence supporting its use in hemodialysis patients is limited. Our aim was to examine outcomes after warfarin therapy initiation, relative to no warfarin use, following incident AF in a large cohort of hemodialysis patients who had comprehensive prescription drug coverage through Medicare Part D. STUDY DESIGN: Retrospective observational cohort study. SETTING & PARTICIPANTS: Patients in the US Renal Data System undergoing maintenance hemodialysis who had AF newly diagnosed in 2007 to 2011, with Medicare Part D coverage, who had no recorded history of warfarin use. PREDICTOR: Warfarin therapy initiation, identified by a filled prescription within 30 days of the AF event. OUTCOMES: Death, ischemic stroke, hemorrhagic stroke, severe gastrointestinal bleeding, and composite outcomes. MEASUREMENTS: HRs estimated by applying Cox regression to an inverse probability of treatment and censoring-weighted cohort. RESULTS: Of 12,284 patients with newly diagnosed AF, 1,838 (15%) initiated warfarin therapy within 30 days; however, ∼70% discontinued its use within 1 year. In intention-to-treat analyses, warfarin use was marginally associated with a reduced risk of ischemic stroke (HR, 0.68; 95% CI, 0.47-0.99), but not with the other outcomes. In as-treated analyses, warfarin use was associated with reduced mortality (HR, 0.84; 95% CI, 0.73-0.97). LIMITATIONS: Short observation period, limited number of nonfatal events, limited generalizability of results to more affluent patients. CONCLUSIONS: In hemodialysis patients with incident AF, warfarin use was marginally associated with reduced risk of ischemic stroke, and there was a signal toward reduced mortality in as-treated analyses. These results support clinical equipoise regarding the use of warfarin in hemodialysis patients and underscore the need for randomized trials to fill this evidence gap.
BACKGROUND: Although warfarin is indicated to prevent ischemic strokes in most patients with atrial fibrillation (AF), evidence supporting its use in hemodialysis patients is limited. Our aim was to examine outcomes after warfarin therapy initiation, relative to no warfarin use, following incident AF in a large cohort of hemodialysis patients who had comprehensive prescription drug coverage through Medicare Part D. STUDY DESIGN: Retrospective observational cohort study. SETTING & PARTICIPANTS: Patients in the US Renal Data System undergoing maintenance hemodialysis who had AF newly diagnosed in 2007 to 2011, with Medicare Part D coverage, who had no recorded history of warfarin use. PREDICTOR: Warfarin therapy initiation, identified by a filled prescription within 30 days of the AF event. OUTCOMES: Death, ischemic stroke, hemorrhagic stroke, severe gastrointestinal bleeding, and composite outcomes. MEASUREMENTS: HRs estimated by applying Cox regression to an inverse probability of treatment and censoring-weighted cohort. RESULTS: Of 12,284 patients with newly diagnosed AF, 1,838 (15%) initiated warfarin therapy within 30 days; however, ∼70% discontinued its use within 1 year. In intention-to-treat analyses, warfarin use was marginally associated with a reduced risk of ischemic stroke (HR, 0.68; 95% CI, 0.47-0.99), but not with the other outcomes. In as-treated analyses, warfarin use was associated with reduced mortality (HR, 0.84; 95% CI, 0.73-0.97). LIMITATIONS: Short observation period, limited number of nonfatal events, limited generalizability of results to more affluent patients. CONCLUSIONS: In hemodialysis patients with incident AF, warfarin use was marginally associated with reduced risk of ischemic stroke, and there was a signal toward reduced mortality in as-treated analyses. These results support clinical equipoise regarding the use of warfarin in hemodialysis patients and underscore the need for randomized trials to fill this evidence gap.
Authors: Valentin Fuster; Lars E Rydén; David S Cannom; Harry J Crijns; Anne B Curtis; Kenneth A Ellenbogen; Jonathan L Halperin; Jean-Yves Le Heuzey; G Neal Kay; James E Lowe; S Bertil Olsson; Eric N Prystowsky; Juan Luis Tamargo; Samuel Wann; Sidney C Smith; Alice K Jacobs; Cynthia D Adams; Jeffery L Anderson; Elliott M Antman; Jonathan L Halperin; Sharon Ann Hunt; Rick Nishimura; Joseph P Ornato; Richard L Page; Barbara Riegel; Silvia G Priori; Jean-Jacques Blanc; Andrzej Budaj; A John Camm; Veronica Dean; Jaap W Deckers; Catherine Despres; Kenneth Dickstein; John Lekakis; Keith McGregor; Marco Metra; Joao Morais; Ady Osterspey; Juan Luis Tamargo; José Luis Zamorano Journal: Circulation Date: 2006-08-15 Impact factor: 29.690
Authors: Craig T January; L Samuel Wann; Joseph S Alpert; Hugh Calkins; Joaquin E Cigarroa; Joseph C Cleveland; Jamie B Conti; Patrick T Ellinor; Michael D Ezekowitz; Michael E Field; Katherine T Murray; Ralph L Sacco; William G Stevenson; Patrick J Tchou; Cynthia M Tracy; Clyde W Yancy Journal: J Am Coll Cardiol Date: 2014-03-28 Impact factor: 24.094
Authors: Stephen L Seliger; Daniel L Gillen; W T Longstreth; Bryan Kestenbaum; Catherine O Stehman-Breen Journal: Kidney Int Date: 2003-08 Impact factor: 10.612
Authors: Alan S Go; Elaine M Hylek; Yuchiao Chang; Kathleen A Phillips; Lori E Henault; Angela M Capra; Nancy G Jensvold; Joe V Selby; Daniel E Singer Journal: JAMA Date: 2003-11-26 Impact factor: 56.272
Authors: Tara I-Hsin Chang; Sai Liu; Medha Airy; Jingbo Niu; Mintu P Turakhia; Jennifer E Flythe; Maria E Montez-Rath; Wolfgang C Winkelmayer Journal: Clin J Am Soc Nephrol Date: 2019-06-07 Impact factor: 8.237
Authors: Salina P Waddy; Allen J Solomon; Adan Z Becerra; Julia B Ward; Kevin E Chan; Chyng-Wen Fwu; Jenna M Norton; Paul W Eggers; Kevin C Abbott; Paul L Kimmel Journal: J Am Soc Nephrol Date: 2020-02-20 Impact factor: 10.121
Authors: Emelia J Benjamin; Michael J Blaha; Stephanie E Chiuve; Mary Cushman; Sandeep R Das; Rajat Deo; Sarah D de Ferranti; James Floyd; Myriam Fornage; Cathleen Gillespie; Carmen R Isasi; Monik C Jiménez; Lori Chaffin Jordan; Suzanne E Judd; Daniel Lackland; Judith H Lichtman; Lynda Lisabeth; Simin Liu; Chris T Longenecker; Rachel H Mackey; Kunihiro Matsushita; Dariush Mozaffarian; Michael E Mussolino; Khurram Nasir; Robert W Neumar; Latha Palaniappan; Dilip K Pandey; Ravi R Thiagarajan; Mathew J Reeves; Matthew Ritchey; Carlos J Rodriguez; Gregory A Roth; Wayne D Rosamond; Comilla Sasson; Amytis Towfighi; Connie W Tsao; Melanie B Turner; Salim S Virani; Jenifer H Voeks; Joshua Z Willey; John T Wilkins; Jason Hy Wu; Heather M Alger; Sally S Wong; Paul Muntner Journal: Circulation Date: 2017-01-25 Impact factor: 29.690