title: Risk of Bleeding and Thrombosis in Patients 70 Years or Older Using Vitamin K Antagonists.
abstract: Previous studies have shown that, despite the higher risk of bleeding, the elderly still benefit from taking anticoagulants if they have a stringent indication. However, owing to the relatively low number of patients older than 90 years in these studies, it is unknown whether this benefit is also seen with the eldest patients.
  
  
  
  To determine how the risk of bleeding and thrombosis is associated with age in patients older than 70 years who were treated with a vitamin K antagonist (VKA).
  
  
  
  A matched cohort study was conducted of patients at a thrombosis service who were treated with a VKA between January 21, 2009, and June 30, 2012. All 1109 patients 90 years or older who were treated with a VKA were randomly matched 1:1:1 with 1100 patients aged 80 to 89 years and 1104 patients aged 70 to 79 years based on duration of VKA treatment. Data analysis was conducted from April 2015 to April 2016.
  
  
  
  The primary outcome was a composite of clinically relevant nonmajor and major bleeding. Secondary outcomes included thromboses and quality of VKA control.
  
  
  
  During 6419 observation-years, 713 of the 3313 patients (1394 men and 1919 women) had 1050 bleeding events. The risk of bleeding was not significantly increased in patients aged 80 to 89 years (event rate per 100 patient-years [ER], 16.7; hazard ratio [HR], 1.07; 95% CI, 0.89-1.27) and mildly increased in patients 90 years or older (ER, 18.1; HR, 1.26; 95% CI, 1.05-1.50) compared with patients aged 70 to 79 years (ER, 14.8). The point estimates for major bleeding (including fatal) were comparable for patients aged 80 to 89 years (ER, 1.0; HR, 1.09; 95% CI, 0.60-1.98) and those 90 years or older (ER, 1.1; HR, 1.20; 95% CI, 0.65-2.22) compared with those aged 70 to 79 years (ER, 0.9). The increase in bleeding risk was sharper in men than in women. Eighty-five patients (2.6%) developed a thrombotic event. Risk of thrombosis was higher for patients in their 90s (HR, 2.14; 95% CI, 1.22-3.75) and 80s (HR, 1.75; 95% CI, 1.002-3.05) than for patients in their 70s. Vitamin K antagonist control became significantly poorer with rising age, which partly explained the increased bleeding risk in patients 90 years or older, but most of the increased risk of thrombosis was not mediated by VKA control.
  
  
  
  These clinical practice data of patients considered eligible for anticoagulation show that the bleeding risk with a VKA only mildly increases after the age of 80 years, while there is a sharp increase in the risk of thrombosis in the same age group.
authors.affiliation: Division of Hemostasis and Thrombosis, Department of Hematology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands2Certe Thrombosis Service Groningen, Groningen, the Netherlands.
authors.forename: Hilde A M
authors.initials: HA
authors.lastname: Kooistra
authors.affiliation: Department of Internal Medicine, Medical Center Leeuwarden, Leeuwarden, the Netherlands.
authors.forename: Agneta H
authors.initials: AH
authors.lastname: Calf
authors.affiliation: Division of Hemostasis and Thrombosis, Department of Hematology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands2Certe Thrombosis Service Groningen, Groningen, the Netherlands.
authors.forename: Margriet
authors.initials: M
authors.lastname: Piersma-Wichers
authors.affiliation: Division of Hemostasis and Thrombosis, Department of Hematology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Hanneke C
authors.initials: HC
authors.lastname: Kluin-Nelemans
authors.affiliation: University Center for Geriatric Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Gerbrand J
authors.initials: GJ
authors.lastname: Izaks
authors.affiliation: Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Nic J G M
authors.initials: NJ
authors.lastname: Veeger
authors.affiliation: Division of Hemostasis and Thrombosis, Department of Hematology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Karina
authors.initials: K
authors.lastname: Meijer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D000925:Anticoagulants / Q000009:adverse effects*; D015331:Cohort Studies; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced*; D006801:Humans; D008297:Male; D016016:Proportional Hazards Models; D012307:Risk Factors; D054556:Venous Thromboembolism / Q000139:chemically induced*; D014812:Vitamin K / Q000009:adverse effects* / Q000037:antagonists & inhibitors*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000925:Anticoagulants; D014812:Vitamin K