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.
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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. |
Professional Abstract
Objective
To compare the risks and patient-reported outcomes of two treatment strategies for preventing recurrent venous thromboembolism (VTE) among patients who received at least three months of treatment for a VTE
Study Design
| Design Element | Description |
|---|---|
| Design | Observational: cohort study |
| Population | Data from electronic health records for 38,062 adults ages 18 and older who had a diagnosis of a VTE between January 1, 2010, and December 31, 2018, and who received at least 3 months of anticoagulation treatment |
| Interventions/ Comparators |
Treatment strategy 1:
Treatment strategy 2:
|
| Outcomes |
Primary: recurrent VTE, hospitalization for bleeding, all-cause deaths Secondary: treatment satisfaction, health-related quality of life |
| Timeframe | Up to 10-year follow-up for primary outcomes |
This retrospective cohort study compared the effectiveness of receiving versus not receiving extended anticoagulation treatment on preventing recurrent VTE, reducing the risk of hospitalization for bleeding, and reducing all-cause deaths among patients with VTE. Researchers also compared the effect of extended treatment with warfarin versus direct acting oral anticoagulants (DOACs) on clinical and patient-reported outcomes.
The study included electronic health record data for 38,062 adults receiving care at Kaiser Permanente Northern and Southern California between 2010 and 2018. Among patients, 73% were White, 15% were Black or African American, 5% were Asian or Pacific Islander, and 7% identified as other or unknown race; 17% were Hispanic. The average age was 64, and 50% were female.
Researchers identified patients with a VTE diagnosis who filled a three-month prescription for anticoagulation treatment. Among these patients, researchers identified patients who received extended anticoagulation treatment, or treatment after the initial three-month prescription, and compared them to patients who stopped treatment after three months.
To assess patient-reported outcomes, a subset of 5,017 patients diagnosed with VTE between 2015 and 2018 and receiving extended treatment completed surveys about treatment satisfaction and health-related quality of life. Researchers compared outcomes among patients treated with warfarin versus DOACs.
People with VTE, family members, clinicians, and health system administrators gave input during the study.
Results
Compared with patients not receiving extended treatment, patients receiving extended treatment had an unexpected increased risk of recurrent VTE (adjusted hazard ratio [aHR] = 1.41; 95% confidence interval [CI]: 1.22, 1.62). Patients receiving extended treatment also had an increased risk of hospitalization for bleeding (aHR = 1.35; 95% CI: 1.01, 1.8) but a lower risk for all-cause death (aHR = 0.46; 95% CI: 0.41, 0.52).
Among patients receiving anticoagulation treatment for more than six months, patients receiving DOACs had a lower risk of recurrent VTE than patients receiving warfarin (aHR = 0.66; 95% CI: 0.52, 0.82). Risk of hospitalization for bleeding and all-cause death did not differ significantly between patients receiving warfarin versus DOACs.
In surveys, patients receiving DOACs reported higher satisfaction with treatment than patients receiving warfarin (p<0.05). Health-related quality of life did not differ significantly between groups.
Limitations
Researchers did not randomize patients to a treatment strategy, and unmeasured differences between treatment groups may have affected the results. Patients prescribed extended treatment may have been at higher risk for recurrent VTE, leading to the higher observed VTE rates.
Conclusions and Relevance
In this study, patients receiving extended anticoagulation treatment had a paradoxically higher risk for recurrent VTE, possibly due to unmeasured baseline differences among patients. Among patients receiving extended anticoagulation treatment, DOACs were associated with a lower risk of recurrent VTE and higher treatment satisfaction than warfarin.
Future Research Needs
Future research could further examine the impact of extended anticoagulation treatment, accounting for potential unmeasured differences between treatment groups.
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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. |
COVID-19-Related Study
Summary
This study received additional funding in 2020 to quickly initiate new research related to COVID-19. The additional research is in progress. PCORI will post the research findings on this page once the results are final.
COVID-19 appears to affect blood clotting and may increase the risk of venous thromboembolism, or VTE. VTE occurs when blood clots develop inside veins. These blood clots can cause serious health problems or even death among patients in the hospital.
With this enhancement, the research team will compare the risk of VTE for patients in the hospital with and without COVID-19. The team will also look at how the risk of VTE may differ for certain groups of patients. These groups include older adults, men, patients who’ve had VTE before, and patients with severe COVID-19.
Enhancement Award Amount: $500,000
Final Research Report
View this project's final research report.
Journal Citations
Results of This Project
Related Journal Citations
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.