Clinical scenarios for reduced-dose anticoagulants

James Douketis, MD, is a professor of medicine at McMaster University and staff physician in general internal medicine and clinical thromboembolism at St. Joseph’s Healthcare Hamilton. He is the immediate past president of Thrombosis Canada.

Can you think of any clinical scenarios when we should consider using a reduced dose of an anticoagulant?

James Douketis, MD: Yes, there are a number of scenarios where, if you’re using an anticoagulant—and I’m referring again to the direct oral anticoagulants (DOACs), because with the vitamin K antagonists, they should always be administered to have a target international normalized ratio (INR) between 2 and 3, and there’s very little evidence that a lower-dose, lower-intensity anticoagulation, with the exception of patients who may have some of the newer mechanical heart valves, the On-X valves, in whom you can sometimes use a lower-intensity warfarin, but for most other situations, the intensity is the same.

When we have the DOACs, we have generally standard doses, and we have low doses. Low doses tend to be safer and associated with less bleeding, but we want to make sure that they are still effective to prevent stroke, to prevent thrombosis, so we would use a lower dose regimen of a DOAC in a patient who has had idiopathic or unprovoked thrombosis over the long term. Let’s say they want to be on treatment indefinitely, maybe in some cases for the rest of their life—we we’d rather use a low dose DOACs in that situation.

Another situation may be in patients who have severely impaired renal function. If they’re maybe on dialysis or if their creatinine clearance is <30 mL/min, there are emerging data to suggest the safety of using a DOAC. Specifically, apixaban with a dose of up to 2.5 mg bid may be safe to use in those patients with end-stage renal disease to reduce their risk for bleeding and also to be effective.

The third situation may be in patients who have chronic coronary or peripheral arterial disease. In those situations we would use an even lower dose of a DOAC, and I’m referring to rivaroxaban 2.5 mg bid. Normally the dose is 20 mg once a day, so instead of 20 mg/d we’re down to 5 mg/d. But that dose is used in combination with aspirin.

So, there are situations where a low-dose DOAC would be helpful, and of course there are going to be other situations like patients who have had bleeding, where you’re concerned, “I’m going to put them back on the anticoagulant, but maybe I’ll start them on a lower dose and make sure they don’t bleed on that before I increase the dose to the standard dose.”