Date of Award

Spring 5-2026

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Computational and Data Sciences

First Advisor

Cyril Rakovski

Second Advisor

Adrian Vajiac

Third Advisor

Ehsan Yaghmaei

Abstract

Antiphospholipid syndrome (APS) is a chronic autoimmune condition characterized by an increased risk of both arterial and venous blood clots, leading to significant health complications and even death. While warfarin has traditionally been the go-to anticoagulant for most patients with APS, many clinicians are now turning to direct oral anticoagulants (DOACs). However, there's still a lot of uncertainty about how effective these newer medications are compared to warfarin, especially for patients who are considered high-risk. The randomized studies we have are somewhat limited and might not reflect the diverse experiences of patients in the real world.

In my dissertation, I used extensive electronic health record (EHR) data to explore the impact of different anticoagulant options on mortality rates in adults diagnosed with APS. I analyzed de-identified EHR data from Oracle Health, creating a scenario similar to a clinical trial where patients started either warfarin or a DOAC at a specific point in their treatment. To address potential biases that could have influenced the results, I employed advanced statistical methods, including targeted maximum likelihood estimation (TMLE) with Super Learner techniques. My primary focus was on the difference in one-year all-cause mortality risk, but I also looked at long-term outcomes up to five years and examined differences across various patient subgroups.

The results indicated that starting DOAC therapy was linked to a higher estimated risk of death within the first year compared to warfarin, even after adjusting for various confounding factors. This difference was especially notable in the earlier follow-up period and less pronounced as VI

time went on, with only minor differences observed after three to five years. Interestingly, the analysis showed that patients who had experienced an arterial clot before had a significantly higher risk, reinforcing the notion that certain APS patients are at greater risk.

Overall, these findings bolster the idea that warfarin should still be the preferred treatment for APS, particularly in the early stages and among patients who are at higher risk. Beyond this specific conclusion, my work highlights how we can use sophisticated methods to analyze complex EHR data, ultimately providing valuable insights in circumstances where traditional clinical trials may not be feasible. Complementary descriptive analyses using the IQVIA national claims database document a 40 percent rise in APS incidence between 2019 and 2024, pronounced geographic and socioeconomic disparities in diagnosis, and a 50- to 60-fold drug cost differential favoring warfarin over DOACs — findings that contextualize the clinical results and strengthen the policy case for warfarin as the preferred anticoagulant in this population.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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