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891 The Bleeding Risk of Vitamin K Antagonists Hardly Increases after the Age of 80 Years: Data from a Large Real-Life Cohort StudyClinically Relevant Abstract

Antithrombotic Therapy
Program: Oral and Poster Abstracts
Type: Oral
Session: 332. Antithrombotic Therapy II
Monday, December 7, 2015: 6:45 PM
W307, Level 3 (Orange County Convention Center)

Hilde Kooistra, MD1,2*, Agneta Calf, MD3*, Margriet Piersma-Wichers, MD1,2*, Gerbrand Izaks, MD4*, Nic Veeger, MSc5* and Karina Meijer, MD, PhD6

1Certe Thrombosis Service Groningen, Groningen, Netherlands
2Division of Hemostasis and Thrombosis, Department of Hematology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
3Department of Internal Medicine, Medical Center Leeuwarden, Leeuwarden, Netherlands
4University Center for Geriatric Medicine, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
5Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
6Division of Hemostasis and Thrombosis, Department of Hematology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands

Introduction: Many physicians are reluctant to prescribe anticoagulants in the elderly, because of the increased bleeding risk. On the other hand, the potential benefit of anticoagulants also increases as the thrombotic risk rises as well. The BAFTA-trial demonstrated that patients over 75 years still benefit from vitamin K antagonists (VKA) use for atrial fibrillation, and the RIETE-study showed that patients over 80 years have a higher risk to die of recurrent thrombosis than of bleeding while on VKA. However, even in these studies the number of nonagenarians was low. Given the aging population, data on the real-life safety and efficacy of VKA in these very old patients are urgently needed.

Aim: To determine the safety and efficacy of VKA in octogenarians and nonagenarians compared to septuagenarians.

Methods: We selected all nonagenarians from a consecutive cohort of 26,089 patients treated with VKA at Certe Thrombosis Service Groningen (2009-2012). Subsequently, every nonagenarian was randomly matched with one septuagenarian and one octogenarian. The primary endpoint was bleeding events (clinically relevant non-major and major). Secondary endpoints were thrombotic events, VKA related deaths, and quality of VKA control. All events were adjudicated by two experienced physicians who were unaware of age. The relation with age was analyzed in Cox regression models, septuagenarians being the reference group.

Results: In total, 3313 patients were included. The 713 patients (22%) with at least one bleeding event had in total 986 clinically relevant and 64 major bleeding events (Table 1). The bleeding risk of the octogenarians (HR 1.07; CI 0.89-1.27) was comparable with the septuagenarians. Nonagenarians had a mildly increased risk (HR 1.26; CI 1.05-1.50), and a non-significantly higher risk of major bleeding (HR 1.20; CI 0.65-2.22) and fatal bleeding (HR 1.32; 0.58-3.01). The outcomes of the analyses in the inception cohort did not differ essentially from the main analyses.

The risk to develop a thrombosis was higher in the nonagenarians (HR 2.14; CI 1.22-3.75) and octogenarians (HR 1.75; CI 1.002-3.05), and this was even more pronounced in the inception cohort (HR 5.57; CI 1.22-25.4 and HR 5.00;CI 1.10-22.8, respectively). The risk of thrombosis related death was also increased in the nonagenarians (HR 4.53; CI 1.94-10.5).

The control of individual time in the therapeutic range and variability became significantly poorer with rising age (Table 1). Interestingly, the time under and above the range remained well balanced. The increased bleeding risk of nonagenarians reduced from 1.26 to 1.16 (CI 0.96-1.39) after correction for VKA control. In contrast, the increased thrombotic risk was independent of VKA control. Thus, VKA users over 80 years probably had a relatively high baseline thrombotic risk compared to their bleeding risk.

The number of thrombotic events (20) was comparable with the number of major bleeds (22) in the septuagenarians. However, the thrombotic events (32 and 33, respectively) outweighed the major bleeding rate (20 and 22, respectively) in the nonagenarians and octogenarians. 

Conclusion: In this real-life cohort study, the bleeding risk was not increased in octogenarians and only mildly increased in nonagenarians, compared to septuagenarians. Moreover, the thrombotic risk outweighed the bleeding risk in both octogenarians and nonagenarians. Therefore, any age, even above 90 years, should in itself not be a reason to withhold anticoagulants.

Table 1: Clinical endpoints

70-79 years

80-89 years

≥ 90 years

No. of patients

1104

1100

1109

Years of observation

2386

2264

1769

Total number of bleeds (major)

353 (22)

377 (22)

320 (20)

     -  Skin

89 (0)

120 (0)

118 (1)

     -  Nose

67 (0)

79 (0)

70 (0)

     -  Urogenital tract

77 (0)

67 (1)

41 (1)

     -  Gastrointestinal tract

59 (6)

59 (7)

54 (12)

     -  Conjunctiva

18 (0)

17 (0)

15 (0)

     -  Lung

10 (0)

15 (1)

11 (1)

     -  Intracranial

11 (11)

10 (10)

5 (5)

     -  Others

22 (5)

10 (3)

6 (0)

Total number of thrombotic events

20

33

32

     -  Ischemic stroke

8

10

14

     -  Unspecified stroke

1

7

10

     -  VTE

1

0

2

     -  Myocardial infarction

10

16

6

Death, related to VKA treatment

18

18

36

            - Due to bleeding

11

12

12

            - Due to thrombosis

7

6

24

Quality of VKA control

     - Mean time in the therapeutic range (%)

73.5

71.1

66.4

     - Time above (%)

14.5

15.1

17.4

     - Time below (%)

12.0

13.7

16.2

     - Mean INR

2.93

2.90

2.93

     - Variability

2.02

2.86

4.56

Disclosures: Kooistra: Bayer Healthcare: Other: travel support . Piersma-Wichers: Pfizer: Speakers Bureau ; Leo Pharma: Other: travel support ; Boehringer Ingelheim: Speakers Bureau ; GlaxoSmithKline: Speakers Bureau ; Bayer Healthcare: Other: travel support . Meijer: Baxter: Other: travel support , Research Funding ; Sanquin: Other: travel support , Research Funding , Speakers Bureau ; Bayer Healthcare: Other: travel support , Research Funding , Speakers Bureau ; Pfizer: Other: travel support .

*signifies non-member of ASH