Risk of Falls and Major Bleeds when on Oral Anticoagulants

Abstract & Commentary

By Rahul Gupta, MD, MPH, FACP

Clinical Assistant Professor, West Virginia University School of Medicine, Charleston, WV

Dr. Gupta reports no financial relationships relevant to this field of study.

Synopsis: Patients on oral anticoagulants at high risk of falls did not have significantly increased risk of major bleeds.

Source: Donze J, et al. Risk of falls and major bleeds in patients on oral anticoagulation therapy. Am J Med 2012;125: 773-778.

THE EFFECTIVENESS OF ORAL ANTICOAGULATION THERApy has been clearly established in prevention and treatment of a variety of cardiovascular and cerebrovascular conditions. As commonly as they are prescribed, a careful consideration of the risks and benefits of therapy always precedes the decision to initiate an oral anticoagulant, often regardless of the age. However, the prevalence of the two most common indications for such treatment with oral anticoagulants, atrial fibrillation (AF) and venous thromboembolism (VTE), actually rises with age. The most common reason cited for not providing oral anticoagulants to the elderly is a risk of falls.1 For example, studies have documented that elderly individuals with AF are often either undertreated or not treated at all with oral anticoagulant therapy, thus denying one of the most effective stroke prevention therapies to this population group.2 However, some studies have suggested that older individuals are at greater risk of bleeding than their younger counterparts with similar diagnoses.3 Because patients at high risk for falls are often excluded from prospective, clinical anticoagulation therapy trials, only limited retrospective data are available on the issue.

In their research, Donze et al utilized data sets from a prospective cohort study conducted at a Swiss university hospital from January 2008 to March 2009. All consecutive adult inpatients and outpatients discharged on oral vitamin K antagonists (VKA) were eligible to be included in the study. The outcome measured was the time to a first major bleed within 12 months of follow-up. Out of the 650 eligible patients, 515 were enrolled in the study and 35 suffered a first major bleed during the follow-up period (7.5 per 100 patient-years). The median age was 71.2 years and 63.9% were men. A total of 308 patients (59.8%) were identified to be at high risk of falls based on screening questions. Patients at high risk of falls had a non-significantly higher crude incidence rate of major bleeds than patients at low risk of falls (8.0 vs 6.8 per 100 patient-years, P = 0.64). In multivariate analysis, a high falls risk was not statistically significantly associated with the risk of a major bleed. Overall, the main bleeding location was gastrointestinal tract and only three major bleeds occurred directly after a fall (incidence rate: 0.6 per 100 patient-years). The researchers concluded that being at risk of falls is not a valid reason to avoid oral anticoagulation in elderly medical patients. However, as expected, polypharmacy was found to be independently associated with a high risk of major bleeds in the study. A possible explanation could include a higher risk of drug interactions in patients on oral anticoagulants.

Commentary

Studies have documented that oral anticoagulation therapy is withheld more frequently in elderly patients than in younger patients with identical elective indications. Perhaps due to the perceived age-related increase in bleeding complications, physicians remain reluctant to treat elderly patients as enthusiastically with oral anticoagulants. The study by Donze et al adds to the evidence that being at risk for falls should not be a valid reason to avoid oral anticoagulation in the elderly population. In this study, not only was the incidence of major bleeds found to be significantly lower than expected, but also only three major bleeds occurred directly after a fall. The Fang et al3 study of a large Kaiser Permanente database showed that, regardless of whether individuals were on oral anticoagulants, progressive age increased the risk of major bleeding. It raises the question whether age is simply a marker for an increased risk of bleeding. This would mean that other concomitants of aging, such as comorbid conditions and polypharmacy, may be to blame. Therefore, it would be fair to assume that the process of aging, regardless of being on anticoagulant therapy, appears to be a marker for a greater risk of bleeding, under which circumstances age would certainly represent a higher risk for those on oral anticoagulants. It remains unclear, however, whether age itself is an independent risk factor for increased risk of bleeding. Although this study will not resolve the debate, it certainly assists in expanding our understanding of the complex relationship of age to the use of oral anticoagulant therapy. As a result of this research, physicians should feel more comfortable in treating the elderly while attempting to minimize the modifiable risk factors.

Although the research conducted by Donze et al studied patients on VKA, it may be worthwhile mentioning another issue — the use of new, targeted oral thrombin and factor Xa inhibitors in the elderly. Although specific analysis of age as a risk for major bleeding has not been done, the limited data have found the overall incidence of major bleeding to be similar to or lower than warfarin. Additionally, a consistent lower incidence rate of intracranial hemorrhage has been found with these newer agents compared to warfarin, which should be good news in the elderly.

In essence, oral anticoagulation therapy should not be withheld from the elderly simply because of age. Well-managed oral anticoagulation therapy when optimally used in clinical practice can achieve substantial benefit. I would stay tuned to the data on the effect of age and outcomes with the newer oral anticoagulants.

References

1. Garwood CL, Corbett TL. Ann Pharmacother 2008;42: 523-532.

2. Brophy MT, et al. J Am Geriatr Soc 2004;52:1151-1156.

3. Fang MC, et al. J Am Geriatr Soc 2006;54:1231-1236.