Vitamin K antagonist use associated with higher risk of thrombosis than bleeding in patients ages 80 and older

Bleeding risk with a vitamin K antagonist (VKA) may mildly increase after the age of 80 years, and there may also be a sharp increase in the risk of thrombosis in the same age group, a study found.

Researchers conducted a matched cohort study of patients at a thrombosis service in the Netherlands. A total of 1,109 patients ages 90 years or older who were treated with a VKA were randomly matched 1:1:1 with 1,100 patients ages 80 to 89 years and 1,104 patients ages 70 to 79 years based on duration of treatment. The primary outcome was a composite of clinically relevant nonmajor and major bleeding. Secondary outcomes included thromboses and quality of VKA control. Results were published July 5 by JAMA Internal Medicine.

Compared with patients ages 70 to 79 years, those ages 80 to 89 years had a similar risk of bleeding, whereas patients ages 90 years or older had a mildly increased risk of bleeding, the study found. Patients in their 80s and 90s had a markedly higher risk of thrombosis than did patients in their 70s.

During 6,419 observation-years, 713 of the 3,313 patients had 1,050 bleeding events. Patients ages 70 to 79 years had an event rate per 100 patient-years (ER) of 14.8. The risk of bleeding was not significantly increased in patients ages 80 to 89 years (ER, 16.7; hazard ratio [HR], 1.07; 95% CI, 0.89 to 1.27) and was mildly increased in patients ages 90 years or older (ER, 18.1; HR, 1.26; 95% CI, 1.05 to 1.50). The point estimate of event rates for major bleeding, including fatal bleeds, for those ages 70 to 79 years was 0.9, which was comparable with those for patients ages 80 to 89 years (ER, 1.0; HR, 1.09; 95% CI, 0.60 to 1.98) and ages 90 years or older (ER, 1.1; HR, 1.20; 95% CI, 0.65 to 2.22) .

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 to 3.75) and 80s (HR, 1.75; 95% CI, 1.002 to 3.05) than for patients in their 70s. VKA control became significantly poorer as age increased, which partly explained the increased bleeding risk in patients ages 90 years or older but not the increased risk of thrombosis, the authors wrote.

An editorial concluded that clinicians are successfully identifying very old patients who can be given anticoagulation with relative safety. However, researchers know little about patients whom clinicians choose not to treat with anticoagulation.

“The specter of iatrogenic hemorrhage and preventable thrombosis looms large when discussing anticoagulation at any age,” the editorial concluded. “Patients and clinicians will benefit greatly from robust and generalizable data when considering these nuanced decisions.”