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In people with blood clots in the leg or certain heart rhythm problems, direct oral anticoagulants reduce deaths due to blood clots or bleeding compared with warfarin

Chai-Adisaksopha C, Hillis C, Isayama T, et al. Mortality outcomes in patients receiving direct oral anticoagulants: a systematic review and meta-analysis of randomized controlled trials. J Thromb Haemost. 2015:2012-20.

Review question

In people with blood clots in the leg or certain heart rhythm problems (mainly atrial fibrillation), do direct oral anticoagulants (one type of “blood thinner”) cause less bleeding than warfarin or other similar blood thinners?


Blood clots in the legs are dangerous because clots can break off and travel within the body, blocking arteries in the lung (pulmonary embolism), causing lung damage or even death.

People with certain heart rhythm problems (e.g., atrial fibrillation) are also at risk for blood clots and stroke due to blood clots.

Anticoagulant drugs, often referred to as “blood thinners,” can prevent blood clots. These drugs can also cause serious bleeding. Some blood thinners may be better than others at preventing clots or may cause less bleeding.

How the review was done

The researchers did a systematic review, searching for studies available up to August, 2015.

They found 13 randomized controlled trials with 103,013 people.

The key features of the trials were:

  • people had blood clots in the leg, a sudden blockage in a lung artery, or heart rhythm problems;
  • people were treated with one type of blood thinner called direct oral anticoagulant drugs (dabigatran, rivaroxaban, apixaban, or edoxaban) for at least 3 months;
  • direct oral anticoagulant drugs were compared with another type of blood thinner called warfarin (or heparin followed by warfarin); and
  • outcomes were measured after 6 to 34 months.

What the researchers found

Compared with warfarin, direct oral anticoagulants reduced the proportion of people who died from blood clots, bleeding, or from any cause.


In people with blood clots in the leg or certain heart rhythm problems, direct oral anticoagulants reduce deaths due to blood clots, bleeding, or any cause compared with warfarin.

Direct oral anticoagulants (DOACs) vs warfarin in people with venous thromboembolism or atrial fibrillation


Number of trials (people)

Rate of events with DOACs*

Rate of events with warfarin

Effects of DOACs

Death from diseases of the heart or blood vessels

12 trials (102,743 people)



About 30 fewer people out of 10,000 died from diseases of the heart or blood vessels.

Death from any cause

13 trials (102,843 people)



About 60 fewer people out of 10,000 died from any cause.

Death from bleeding

12 trials (uncertain number of people)



About 15 fewer people out of 10,000 died from bleeding.



Medications that suppress, delay, or prevent blood clots. Anticoagulants (also referred to as "blood thinners") are used to treat circulatory blockages.
Randomized controlled trials
Studies where people are assigned to one of the treatments purely by chance.
Systematic review
A comprehensive evaluation of the available research evidence on a particular topic.

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