Falls are a main reason why patients with indications for anticoagulation are not provided therapy.1 Patients who fall are often older and more prone to thrombotic complications from disease states, such as atrial fibrillation or venous thromboembolism. In a registry of more than 10,000 patients, 13% had a contraindication to anticoagulation based on physician discretion, with 17% of those patients not given anticoagulation, because of falls.2
Both negative and positive outcomes have been observed in studies evaluating patients who fall with or without resulting head trauma or are at high risk of falling on anticoagulation. Most of the data are with patients on warfarin therapy though newer data for falling patients on direct-acting oral coagulants (DOACs) are being released. Studies examining these patients need scrutiny, as patient populations in cohorts are often heterogeneous.
For example, Banerjee and colleagues reported that patients with atrial fibrillation on anticoagulation and a prior history of falls had significantly more ischemic stroke/thromboembolism and all-cause mortality that those patients without a fall history.3 Interestingly, no difference was found in bleeding or hemorrhagic stroke. The patient populations examined, however, were significantly different based on age and bleeding and thrombotic risk, with worse predisposition in the prior falls cohort. Similar conclusions can be drawn from a study published in the Journal of Trauma and Acute Care Surgery, which found a higher mortality rate in elderly patients with atrial fibrillation who fall on anticoagulation than those who are not on anticoagulation.4 However, it is important to note that there were significantly more falls with head trauma in the anticoagulation arm, which leads to a higher mortality rate. In addition, patient bleeding risk was not calculated at baseline based on scoring systems, such as HAS-BLED. Finally, Coleman and colleagues evaluated traumatic-fall patients who were on anticoagulation and found longer lengths of stay in the intensive care unit (ICU) days after a fall in patients on warfarin compared with no anticoagulation.5 There was no difference in mortality or hemorrhagic strokes.
Opposed to these results was a study by Donzé and colleagues, which found that patients on oral anticoagulation who were at high risk for falling had no significant increase in bleeding compared with low-risk patients.1 The authors concluded that being at risk of falls was not a valid reason to withhold anticoagulation.
DOACs are being used increasingly more often for patients needing anticoagulation for a variety of disease states. Data interpretation with these agents follows a similar pattern to the previous data with warfarin. Rao and colleagues evaluated apixaban use in patients with a fall history as an analysis of the ARISTOTLE trial.6 The study found that patients with falls within the past year had higher major bleeding rates and increased mortality than patients who did not fall. Compared with warfarin, rates of bleeding were significantly reduced with apixaban if patients had falls within the previous year. Significant differences were noted in patient baseline characteristics with a significantly sicker population enrolled in the falls within a 1-year cohort. A pre-specified analysis of the ENGAGE-TIMI 48 trial was recently published comparing edoxaban and warfarin in patients with an increased risk of falls versus those not deemed to be high-risk.7 Similar to other studies, patients in the falls cohort had baseline characteristics making them higher risk for poorer outcomes. Edoxaban was associated with reductions in intracranial hemorrhage and life-threatening bleeding compared with warfarin in patients who fall, but no differences were noted in major bleeding. Overall, there was a greater absolute risk reduction in severe bleeding events and all-cause mortality in patients at increased risk of falling when taking edoxaban versus warfarin. Pozzessere and colleagues evaluated dabigatran compared with warfarin in geriatric patients who fell.8 They found no differences between the 2 agents in terms of hospital length of stay, ICU length of stay, intracranial hemorrhage rates, or mortality. Unlike other studies, there were no major differences in baseline characteristics between the dabigatran and warfarin cohorts. Finally, to date, there has been no specific data published regarding rivaroxaban and falls.
It is important to define what a high-fall risk patient is for those prescribers considering starting or stopping anticoagulation. This is a highly subjective and very difficult proposition, as evidenced by the discretionary data presented above. However, previous studies have tried to answer this question. One such study showed that a patient had to fall 295 times annually for the risk of subdural hematoma to outweigh the beneficial thrombosis reduction with warfarin in atrial fibrillation.9 It is important to note that though patients on anticoagulation have a higher risk of bleeding when they fall, that percentage risk is still low, and studies in patients with atrial fibrillation who had a history of falls documented higher risk of intracranial hemorrhage, regardless of patient use of aspirin, warfarin, or no antithrombotic therapy.10,11 As rates of intracranial bleeding in patients on DOACs is lower than that of warfarin, the fall amount could be hypothesized to be even higher than 295 per year for these agents, though a specific number has not been elicited in trials thus far.
Although, a very difficult decision, the use of anticoagulation in patients with falls seems more beneficial compared with withholding therapy. A shared decision-making process should be undertaken to determine the optimal course of therapy on a patient-by-patient basis. Finally, consultation with a geriatrician regarding weighing the benefits and risks of anticoagulation in this patient population would be advantageous, if available.
1. Donzé J, Clair C, Hug B, et al. Risk of falls and major bleeds in patients on oral anticoagulation therapy. Am J Med. 2012;125(8):773-8. doi: 10.1016/j.amjmed.2012.01.033.
2. O'Brien EC, Holmes DN, Ansell JE, et al. Physician practices regarding contraindications to oral anticoagulation in atrial fibrillation: findings from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) registry. Am Heart J. 2014;167(4):601-609.e1. doi: 10.1016/j.ahj.2013.12.014.
3. Banerjee A, Clementy N, Haguenoer K, Fauchier L, Lip GY. Prior history of falls and risk of outcomes in atrial fibrillation: the Loire Valley Atrial Fibrillation Project. Am J Med. 2014;127(10):972-8. doi: 10.1016/j.amjmed.2014.05.035.
4. Inui TS, Parina R, Chang DC, Inui TS, Coimbra R. Mortality after ground-level fall in the elderly patient taking oral anticoagulation for atrial fibrillation/flutter: a long-term analysis of risk versus benefit. J Trauma Acute Care Surg. 2014;76(3):642-9. doi: 10.1097/TA.0000000000000138.
5. Coleman J, Baldawi M, Heidt D. The effect anticoagulation status on geriatric fall trauma patients. Am J Surg. 2016;212(6):1237-42. doi: 10.1016/j.amjsurg.2016.09.036.
6. Rao MP, Vinereanu D, Wojdyla DM, et al. Clinical outcomes and history of fall in patients with atrial fibrillation treated with oral anticoagulation: insights from the ARISTOTLE trial. Am J Med. 2018;131(3):269-75. doi: 10.1016/j.amjmed.2017.10.036.
7. Steffel J, Giugliano RP, Braunwald E, et al. Edoxaban versus warfarin in atrial fibrillation patients at risk of falling: ENGAGE AF-TIMI 48 Analysis. J Am Coll Cardiol. 2016;68(11):1169-78. doi: 10.1016/j.jacc.2016.06.034.
8. Pozzessere A, Grotts J, Kaminski S. Dabigatran use does not increase intracranial hemorrhage in traumatic geriatric falls when compared with warfarin. Am Surg. 2015;81(10):1039-42.
9. Man-Son-Hing M, Nichol G, Lau A, Laupacis A. Choosing antithrombotic therapy for elderly patients with atrial fibrillation who are at risk for falls. Arch Intern Med. 1999;159(7):677-85.
10. Gage BF, Birman-Deych E, Kerzner R, Radford MJ, Nilasena DS, Rich MW. Incidence of intracranial hemorrhage in patients with atrial fibrillation who are prone to fall. Am J Med. 2005;118(6):612-7.
11. Hagerty T, Rich MW. Fall risk and anticoagulation for atrial fibrillation in the elderly: a delicate balance. Cleve Clin J Med. 2017;84(1):35-40. doi: 10.3949/ccjm.84a.16016.
Alexander Kantorovich, PharmD, BCPS
Alexander Kantorovich, PharmD, BCPS, is a Clinical Associate Professor of Pharmacy Practice at Chicago State University College of Pharmacy and Clinical Pharmacy Specialist at Advocate Christ Medical Center in Oak Lawn, Illinois. Dr. Kantorovich earned his Associate of Science degree with an emphasis in chemistry from William Rainey Harper College and received his Doctor of Pharmacy degree from the University of Illinois at Chicago College of Pharmacy. He went on to complete a 2-year pharmacotherapy residency with an emphasis in cardiology and critical care at the Cleveland Clinic and is board certified in pharmacotherapy. His research interests center around cardiovascular pharmacotherapy, anticoagulation, and anticoagulation reversal.