Thesis in a nutshell – by Yehua Wang
My study focuses on pleiotropic properties of ticagrelor among patients with acute coronary syndrome (ACS). Ticagrelor, prasugrel, and clopidogrel have similar indications and are the three most widely used P2Y12 inhibitors to reduce the risk of recurrent cardiovascular events among patients having survived ACS. Ticagrelor processes some distinct pharmacological properties than prasugrel and clopidogrel. There have been numerous publications discussing the clinical implications of these distinct pharmacological properties, but in pre-clinical settings. I would like to evaluate whether ticagrelor’s properties can confer additional clinical benefits or bring risks compared to its two other counterparts at population level.
The goal of my dissertation is to use administrative claims to assess whether among patients with ACS, ticagrelor, based on its pleiotropic pharmacological properties besides platelet inhibition, can confer (1) more clinical benefits to patients having diabetes as comorbidity in preventing recurrent cardiovascular events than patients starting on prasugrel; (2) reduced bacterial infection risk (especially infections likely caused by Gram-positive bacteria) than those starting on prasugrel; (3) higher risk of statin-associated musculoskeletal syndromes, due to co-exposure to statins, than those starting on prasugrel and clopidogrel.
Inspiration
My dissertation idea was inspired by one of our previous graduate students’ dissertation, in which he explored whether GLP-1 antagonist could reduce the risk of COPD exacerbation. The assumption was established based on the literature review of GLP-1 antagonists’ pharmacological properties and leveraged claim databases to prove the assumption. The clinical topic came from my experience working as a research assistant with Dr. Winterstein, during which I was introduced to the clinical roles of P2Y12 inhibitors and the nuance between these three options in terms of their pharmacological properties and clinical safety and effectiveness profiles.
Real-world data is an important source to generate additional safety and effectiveness evidence not covered by trials and can be useful for drug reporposing/repositioning.
Cool methodological features
To provide a comprehensive picture of study population, I will used both MarketScan (commercial insured populations, typically aged less than 65) and Medicare (senior populations aged 65 or above) for my dissertation aims. Methodologically wise, I will utilize target trial emulation framework for the first two aims for the purpose of a more transparent evidence generation with higher quality. In the aim 3, to adjust for unmeasured confounding factors, I will use self-controlled study design to control for time-fixed factors such as genetic polymorphisms in order to assess the additional muscle-related adverse event risk processed by the addition of ticagrelor.
Impact
I hope my dissertation will provide some translational insights from bench side to patients at bedside for a safer and more effective use of ticagrelor. More specifically, the evidence can help the clinicians make a more informed decision on selecting the most appropriate P2Y12 inhibitors as well as medications co-prescribed such as statins for patients with ACS.
Next steps
I’m looking for an academic position after completion of my dissertation. I wish to use the training I have received at POP and the research experience I gained through working with Dr. Winterstein and the team to prepare myself as a next-generation pharmacoepidemiologist.