Samuel Z. Goldhaber, MD


January 23, 2017

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Hello. This is Dr Sam Goldhaber from Brigham and Women's Hospital and Harvard Medical School in Boston, Massachusetts, speaking for the Clot Blog on at Medscape. I am speaking from the European Society of Cardiology (ESC) 2016 meeting in Rome, Italy. Today I am going to discuss a publication[1] from our inpatient records at Brigham and Women's Hospital concerning novel oral anticoagulants (NOACs) that are not prescribed in the standard dose but rather in the lower dose that is supposed to be reserved for patients with moderately severe chronic kidney disease.

We looked through more than 3 years of our inpatient records and found more than 300 patients who were receiving the lower rather than the standard dose of a NOAC, including dabigatran, rivaroxaban, and apixaban. We did not have enough data in this retrospective study to look at edoxaban.

Our findings were surprising. More than half of the patients receiving these lower doses of NOACs did not have any indication for the lower dose, as listed in the manufacturer labeling recommendations. As we look around the world for reports of lower dosing or underdosing, we see that this is becoming a widespread phenomenon. Certainly, lower doses are prescribed because healthcare providers want to cut down on bleeding complications. The unanswered question is whether, by cutting down on bleeding complications with a lower dose of the NOAC, we are increasing thrombotic complications such as stroke, myocardial infarction, pulmonary embolism, and deep vein thrombosis (DVT).

In this series at Brigham and Women's Hospital, we could not find an indication for the lower dose for more than 50% of the patients. Some of these patients did have chronic kidney disease, but none were severe enough to meet criteria for the lower dose of the NOAC. Some patients had previous histories of gastrointestinal bleeding; others were taking aspirin. Many of the patients in this retrospective study had multiple medical comorbidities and would not ordinarily qualify for the pivotal randomized controlled trials of the NOACs that we use for stroke prevention and atrial fibrillation, or for treatment of DVT and pulmonary embolism. This then brings up the question of real-world patients and real-world experience versus the randomized controlled population.

We believe that the real-world population is often sicker and more fragile than those patients who are eligible to be recruited for a randomized controlled trial. These sicker, more fragile patients, we assume, are at higher risk of bleeding, and this is the reason for underdosing. But is underdosing really the correct dosing for many of these patients? This question remains unanswered. I believe that it highlights the need for getting a lot of information about the lower doses of the NOACs from observational studies, as these patients generally do not qualify for the randomized controlled trials. I believe it is important to track those patients who are receiving the lower doses of NOACs and be certain that we can figure out what the healthcare provider is thinking when prescribing the lower dose.

This is an international phenomenon. A high proportion of patients receiving NOACs are receiving the lower dose, and whether underdosing provides the correct dose in many cases remains to be determined.

This is Dr Sam Goldhaber, signing off for the Clot Blog.


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