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In acute venous thromboembolism, most anticoagulants have similar benefits, but rates of major bleeding vary

Castellucci LA, Cameron C, Le Gal G, et al. Clinical and safety outcomes associated with treatment of acute venous thromboembolism: a systematic review and meta-analysis. JAMA. 2014;312:1122-35.

Review questions

In people with acute (sudden onset) venous thromboembolism, which anticoagulant drugs best reduce recurrence? Which drugs are associated with the least bleeding?

Background

People with venous thromboembolism have blood clots in their veins, usually in the lower leg or thigh. Clots can break off and travel within the body, blocking arteries in the lung (pulmonary embolism) and causing lung damage or even death. Anticoagulant drugs, often referred to as “blood thinners,” can prevent blood clots. These drugs can also cause serious bleeding. Some anticoagulant drugs 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 that were published up to February, 2014.

They found 45 randomized controlled trials with 44,989 people.

The key features of the trials were:

  • people had acute venous thromboembolism with symptoms (people with cancer were excluded);
  • anticoagulant drugs or drug combinations were compared with each other;
  • anticoagulant treatments included unfractionated heparin with a vitamin K antagonist (blocker) (e.g., warfarin, also known as Coumadin® or Jantoven®), low-molecular-weight heparin (LMWH) alone or with a vitamin K antagonist, fondaparinux (Arixtra®) with a vitamin K antagonist, LMWH with dabigatran (Pradaxa®), LMWH with edoxaban (Savaysa®), rivaroxaban (Xarelto®), and apixaban (Eliquis®); and
  • people were treated for 3 to 8 months.

Trials were combined using a type of analysis that lets you compare treatments even if they were not compared directly in the individual trials.

What the researchers found

LMWH alone or with vitamin K antagonists reduced recurrence of clots compared with unfractionated heparin plus vitamin K antagonists.

Apixaban had lower rates of major bleeding compared with any of LMWH, unfractionated heparin, or fondaparinux combined with vitamin K antagonists, or LMWH combined with either dabigatran or edoxaban.

Rivaroxaban had lower rates of major bleeding compared with either LMWH or unfractionated heparin combined with vitamin K antagonists.

Other treatments had similar rates of major bleeding or recurrence of clots.

Conclusions

In people with acute venous thromboembolism, traditional treatment using unfractionated heparin plus vitamin K antagonists performed least well. All newer treatments prevented clots about the same, but there was less major bleeding with rivaroxaban or apixaban.

Low-molecular-weight heparin (LMWH) plus a vitamin K antagonist (VKA) vs other anticoagulant drugs in people with acute venous thromboembolism (VTE)

Comparison anticoagulant drugs

Number of trials*

Absolute effect of LMWH + VKA on recurrent VTE at 6 months†

Number of trials*

Absolute effect of LMWH + VKA on major bleeding at 6 months†

Unfractionated heparin + VKA

22 trials

About 11 fewer patients in 1000 had recurrent VTE

22 trials

No difference in effect

Fondaparinux + VKA

1 trial

No difference in effect

1 trial

No difference in effect

LMWH + dabigatran

2 trials

No difference in effect

2 trials

No difference in effect

LMWH + edoxaban

1 trial

No difference in effect

1 trial

No difference in effect

LMWH alone

3 trials

No difference in effect

2 trials

No difference in effect

Rivaroxaban

2 trials

No difference in effect

2 trials

About 8 more patients in 1000 had major bleeding

Apixaban

1 trial

No difference in effect

1 trial

About 12 more patients in 1000 had major bleeding

*Trials that directly compare the 2 treatments.

†Trials were combined using a type of analysis that lets you compare treatments even if they were not compared directly in the individual trials.



Related Topics


Glossary

Anticoagulants
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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