I worry a great deal when I prescribe anticoagulant or antiplatelet agents to an older, thin patient who appears to be somewhat frail. Most of these patients are elderly women in their mid 80s, living alone and having been widowed some years earlier. Of course, I also worry about their nutritional status and their ability to adhere to the usually complex list of medications they are supposedly taking. Commonly, they are diabetic and have mild to moderate renal insufficiency, as well as reduced serum albumin levels. The reason to consider anticoagulant or antiplatelet therapy is the onset of atrial fibrillation or the documentation of clinical ischemic cardiovascular disease involving the coronary or cerebral circulations. The literature makes it quite clear that such patients are at substantial high risk for hemorrhage when given antiplatelet agents, warfarin, or one of the newer direct oral anticoagulants (DOACs) such as rivaroxaban or apixaban.
It is clear that these patients have blood vessels that are not robust, and that I am going to stress these weakened vessels with antiplatelet or anticoagulant therapy. I am particularly uneasy when such patients require guideline-directed concomitant antiplatelet and anticoagulant agents. Again, the typical patient is an older, somewhat frail woman who is being treated for an acute coronary syndrome or stroke (cerebrovascular accident) and has either just developed atrial fibrillation or has a clear history of having manifested this arrhythmia at an earlier time. Invariably, the atrial fibrillation patients have a high CHA2DS2-VASc score (Congestive heart failure = 1 point, Hypertension = 1 point, Age ≥75 years = 2 points, Diabetes mellitus = 1 point, prior Stroke or transient ischemic attack or thromboembolism = 2 points, Vascular disease = 1 point, Age 65-74 years = 1 point, Sex category [ie, female] = 1 point), and therefore, are at very high risk for a new or recurrent cerebrovascular accident, the most dreaded illness for geriatric patients.
Given this setting, I am sorely tempted to prescribe a reduced dose of a DOAC, assuming that the situation is similar to that found in pediatric practice, where the dose of a particular medication is determined by the patient’s weight. It seems to make sense to me that an elderly woman weighing 100 pounds and with some degree of renal insufficiency should not receive the same dose of a DOAC that a 195-pound similar-aged man with the same diagnosis and the same degree of renal impairment would receive. A rational approach for the lightweight female patient would be to reduce the dose of the DOAC in order to reduce blood levels of the anticoagulant in these individuals with a high risk of bleeding. However, like so many reasonable ideas, this one is not supported by what has so far been reported in the literature. The investigators of the above cited articles could find no evidence that reducing the dose of a DOAC in an elderly and frail individual prevented bleeding. Indeed, in this issue of The American Journal of Medicine, Eschler et al studied more than 1700 anticoagulated patients who were seen in a large Swiss university hospital emergency department during 2018. Twenty percent of these patients were receiving reduced doses of a prescribed anticoagulant, while 12% were receiving excessive doses of this agent. No difference in the likelihood of bleeding on admission to the emergency department could be found among the various groups. Only the concomitant use of aspirin was significantly associated with the presence and higher severity of bleeding.
I searched PubMed for other safety and efficacy reports involving patients who received reduced doses of a DOAC. Only a few reports were found. A large Israeli cohort study examined a large number of atrial fibrillation patients treated with a DOAC for stroke prevention. As many as 39% of these patients were prescribed off-label, reduced doses of an anticoagulant agent, primarily because of a fear of bleeding.
Additionally, the Israeli study found that patients with off-label, reduced doses of a DOAC had a significantly increased risk for the composite outcome of all-cause mortality, stroke, and myocardial infarction, and bleeding rates were not lower in these patients. The findings of Eschler et al +++++published in this issue of the Journal support the Israeli results. Another study from Japan found similar rates of off-label, reduced dosage of DOACs for stroke prophylaxis in atrial fibrillation. However, the authors of the Japanese study did not find higher rates of stroke or death in patients with the off-label, reduced doses.
Given these worrisome findings, I am still quite uneasy when prescribing a full dose of a DOAC to an elderly and somewhat frail geriatric patient of small size. Hopefully, results from further investigation will help alleviate my anxiety or, perhaps, show that a reduced dose of a DOAC might be a good idea in certain clinical situations.
As always, I am happy to hear from readers about this editorial at jalpert@shc.arizona.edu or on our blog at amjmed.org.
To read this article in its entirety please visit our website.
-Joseph S. Alpert, MD
This article originally appeared in the November 2019 issue of The American Journal of Medicine
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