Results Summary

What was the research about?

Each year, more than 100,000 people in the United States die from blood clots that form in their veins and travel to their lungs. Many people who survive a clot will have another one within 10 years. Blood thinners can prevent future clots but may cause problems, such as severe bleeding.

In this study, the research team compared ways to prevent blood clots among people who have already had one. The team compared:

  • People who took warfarin, an older blood thinner, versus newer blood thinners called direct acting oral anticoagulants, or DOACs, for more than six months. Examples of DOACs are apixaban, rivaroxaban, and dabigatran.
  • People who took blood thinners for only three months versus more than three months.

What were the results?

Compared with people who took warfarin, people who took DOACs for more than six months had:

  • A lower risk of another blood clot
  • Higher satisfaction with treatment

People who took warfarin and people who took DOACs didn’t differ in:

  • The risk of a hospital stay for bleeding
  • Death from any cause
  • Quality of life

Compared with people who stopped blood thinners after three months, people who took blood thinners for more than three months had:

  • Higher risk of another blood clot
  • Higher risk of a hospital stay for bleeding
  • Lower risk of death from any cause

The higher risk of another blood clot in people who took blood thinners for more than three months was a surprising finding. Blood thinners probably weren’t the reason for the clots; more research may help explain this finding.

What did the research team do?

The research team reviewed health records for 38,062 adults who had a blood clot between 2010 and 2018. Of these adults, 73 percent were White, 15 percent were Black or African American, 5 percent were Asian or Pacific Islander, and 7 percent were other or unknown race; 17 percent were Hispanic. The average age was 64, and 50 percent were women. All took a blood thinner for at least three months and received care at Kaiser Permanente in California. The team looked at the risk of another blood clot, a hospital stay for bleeding, and death from any cause.

The research team also surveyed a subset of 5,017 patients who took blood thinners for a blood clot between 2015 and 2018. Surveys asked about treatment satisfaction and quality of life.

People with blood clots, family members, doctors, and health system administrators gave input on the study.

What were the limits of the study?

The research team didn’t assign patients by chance to take warfarin or DOACs or tell them how long to take blood thinners. People who stayed on blood thinners longer may have had a higher risk for future blood clots that the team wasn’t able to take into account.

Future research could take into account more factors that affect patients’ risk of blood clots.

How can people use the results?

People who have had a blood clot and their doctors can use the results when considering ways to prevent another blood clot.

PCORI identified long-term use of blood thinner medicines as an important research topic. Blood thinners help prevent blood clots but may cause health problems if taken for a long time. Patients, clinicians, and others wanted to learn: How do different long-term blood thinner treatments compare for patients who have had a blood clot? To help answer this question, PCORI launched an initiative in 2015 on New Oral Anticoagulants (NOACs) in the Extended Treatment of Venous Thromboembolic Disease. The initiative funded this research project and others.

Final Research Report

View this project's final research report.

Peer-Review Summary

Peer review of PCORI-funded research helps make sure the report presents complete, balanced, and useful information about the research. It also assesses how the project addressed PCORI’s Methodology Standards. During peer review, experts read a draft report of the research and provide comments about the report. These experts may include a scientist focused on the research topic, a specialist in research methods, a patient or caregiver, and a healthcare professional. These reviewers cannot have conflicts of interest with the study.

The peer reviewers point out where the draft report may need revision. For example, they may suggest ways to improve descriptions of the conduct of the study or to clarify the connection between results and conclusions. Sometimes, awardees revise their draft reports twice or more to address all of the reviewers’ comments. 

Peer reviewers commented and the researchers made changes or provided responses. Those comments and responses included the following:

  • The reviewers questioned the study results showing higher incidence of venous thromboembolism (VTE) in patients with venous thromboembolic disease when receiving extended treatment with warfarin or direct oral anticoagulants (DOACs) compared to shorter three-month treatment.  The higher incidence was particularly evident between three and six months of treatment but fell after that point. The researchers responded that the factors leading to this counterintuitive finding were likely to be unmeasured confounders, such as whether VTE events were provoked or unprovoked.
  • The reviewers noted that the results could be confounded by differences between groups that were not considered in the analytic model. The researchers acknowledged that several factors predictive of a VTE event could not be measured in this study, such as medication adherence and changes in treatment regimen that are not reflected in prescription changes.
  • The reviewers also asked the researchers for more information on how they calculated propensity scores for their analyses and noted that propensity scores would be more valid if the researchers included any measured confounders in the analyses. The researchers responded that the unmeasured confounders that could not be applied to propensity score calculation would still affect the validity of study results.
  • The reviewers criticized the researchers’ subgroup analyses because the results were presented by subgroup, whereas heterogeneity of treatment effects by subgroup could only be determined by examining the interaction terms in their analytic model. The researchers revised their analyses to include the interaction terms, thereby providing a test of heterogeneity of treatment effects.

Conflict of Interest Disclosures

Project Information

Margaret Fang, MD, MPH
University of California, San Francisco
$3,935,217
10.25302/10.2022.NOACs.151032651
The Comparative Effectiveness of Warfarin and New Oral Anticoagulants for the Extended Treatment of Venous Thromboembolism

Key Dates

July 2016
September 2022
2016
2022

Study Registration Information

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Intervention Strategy Intervention Strategies PCORI funds comparative clinical effectiveness research (CER) studies that compare two or more options or approaches to health care, or that compare different ways of delivering or receiving care. View Glossary
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Last updated: October 18, 2023