CLOT+

Doctor, I have finished 6 months of treatment for my blood clot. Can I start taking a reduced-dose of anticoagulant now?  

After 6 months, some people can safely switch to a reduced dose of a direct oral anticoagulant (DOAC). In these cases, reduced-dose DOACs are just as good at preventing new clots as full-dose DOACs and appear to cause less bleeding. The bleeding risk of reduced-dose DOACs is similar to that of taking a daily aspirin.


Study highlights

People who took reduced-dose DOACs did not have more new blood clots than people who continued to take full-dose DOACs. As well, people who took reduced-dose DOACs had fewer new blood clots than people who switched to placebo or aspirin.

People who took reduced-dose DOACs did not have more serious bleeds than people on placebo or aspirin.

Understanding the problem

Anticoagulants protect people who have DVT or PE from forming new blood clots while their body works on breaking down the old blood clots. How long people with DVT or PE should take an anticoagulant is not based on when the clot is gone. Instead, it is based on when the risk factor that caused the blood clot is gone.

For example, Alice develops a DVT one week after hip replacement surgery. She is treated with anticoagulants for 3 months, and then her doctor tells her she can stop taking them. Alice's risk factor for DVT was surgery. Her DVT is called "provoked".

For many people, the risk factor that caused the DVT or PE is either weak (e.g., travel) or unknown. This type of DVT or PE is called "unprovoked". These people remain at risk for forming new blood clots for the rest of their lives. To protect themselves from another clot, they may decide to take anticoagulants indefinitely.

Anticoagulants also have safety concerns because they increase the risk of bleeding.

For example, Sam has an ulcer in his stomach that is bleeding but so slowly, he hasn't noticed it. When Sam is diagnosed with a PE and starts taking anticoagulants, the bleeding from his ulcer increases and he vomits up blood.

Researchers are always looking for ways to protect people from blood clots while lowering the risk of bleeding. One possible way to do this is to reduce the dose of the anticoagulant. Previous studies showed that reduced-dose DOACs appear to be just as good at preventing new blood clots as full-dose DOACs but with a lower risk of bleeding.

A meta-analysis is a statistical method used to get more accurate information about a treatment by combining the results of studies together. This is similar to judging a sports team based on how they perform over an entire season rather than just one game.

The meta-analysis described below was designed to find out more about how reduced-dose DOACs compare to 1) full-dose DOACs, and 2) stopping DOACs or substituting a DOAC with aspirin.

A summary of 2 studies published up to March 2017.

Who? The studies included 5,847 people who completed 6 to 12 months of full-dose anticoagulation for venous thromboembolism (VTE; collective term for blood clots within the venous system). Patients were excluded if their doctor thought it was unsafe for them to stop anticoagulation or if they had had severe medical illnesses that would prevent them from safely remaining on a full-dose DOAC. Very few patients with cancer were included in the studies.

What? The studies compared reduced-dose DOACs with full-dose DOACs and with placebo or aspirin.


Reduced-dose DOAC

vs

Full-dose DOAC

vsPlacebo or aspirin

Xarelto® 10 mg once a day

OR

Eliquis® 2.5 mg twice a day



Xarelto® 20 mg once a day

OR

Eliquis® 5 mg twice a day





Placebo: A pill containing an inactive substance that has no effect on the outcome. Sometimes, it is referred to as a “sugar pill.”

OR

Aspirin, 81 mg once a day

Reduced-dose DOAC vs full-dose DOAC vs placebo or aspirin in people who have been treated for VTE for 6 months

Outcomes at 1 year

Rate of events with:



Result of reduced-dose DOAC compared with:

Number of studies and quality of the evidence

Reduced-dose DOACFull-dose DOACPlacebo or aspirinFull-dose DOACPlacebo or aspirin

Recurrent VTE

2 out of 100 people 

1 out of 100 people

6 out of 100 people

No difference*

About 4 fewer people who took reduced-dose DOAC had another DVT or PE

Moderate-quality

2 studies

Major Bleeding or Clinically relevant nonmajor bleeding


3 out of 100 people

4 out of 100 people

2 out of 100 people

About 1 less person who took reduced-dose DOAC had bleeding that was life-threatening or required seeing a doctor

No difference*

Moderate-quality to High-quality

2 studies


*Although the rates for the 2 groups look different, the differences were not statistically significant—this means that the difference could simply be due to chance rather than due to the different treatments.


This Evidence Summary is based on the following article:

Vasanthamohan L, Boonyawat K, Chai-Adisaksopha C, et al. Reduced-dose direct oral anticoagulants in the extended treatment of venous thromboembolism: a systematic review and meta-analysis. J Thromb Haemost. 2018 Jul;16(7):1288-1295. doi: 10.1111/jth.14156. Epub 2018 Jun 17. PubMed

Published: Tuesday, October 2, 2018
Last Updated: Thursday, July 30, 2020