Optimal cardiovascular treatment strategies in kidney disease: casual inference from observational data

Fu, E.L. (2021)

Doctoral Thesis

This thesis investigates the effectiveness and safety of treatments in patients with cardiovascular and kidney disease. Routinely collected healthcare data provide an immense opportunity to investigate such questions in populations underrepresented in clinical trials, such as patients with advanced chronic kidney disease (CKD).
The first part of this thesis deals with how to appropriately use routinely collected data to answer causal questions. It illustrates what study designs eliminate commonly occurring biases, namely immortal time and prevalent user bias, and how to use propensity scores to correctly adjust for confounding in the setting of time-fixed and time-varying treatments.
The second part investigates the effectiveness and safety of various treatments. For instance, the effectiveness of beta-blockers in patients with heart failure and advanced CKD is investigated. Renin-angiotensin system inhibitors (RASi) are an especially widely used medication class in CKD patients. The relationship between the magnitude of renal function decline - which is commonly observed after initiation of these drugs - with mortality and cardiorenal outcomes is investigated. In addition, comparative effectiveness study of RASi and calcium channel blockers among patients with advanced CKD is performed. In the last two chapters, a target trial is explicitly emulated to investigate the effect of stopping or continuing RASi and the optimal timing to start dialysis in patients with advanced chronic kidney disease.

• Chronic kidney disease
• Cardiovascular disease
• Dialysis
• Pharmacoepidemiology
• Causal inference
• Routinely collected healthcare data
• Target trial emulation
• Comparative effectiveness and safety
• Confounding and biases
• Time-varying treatments

• All authors: Fu, E.L.
• Supervisor: Dekker, F.W.; Carrero, J.J.
• Co-supervisor: Diepen, M. van
• Committee: Bos, W.J.W.; Rosendaal, F.R.; Steyerberg, E.W.; Swanson, S.A.; Tomlinson, L.A.
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2021-10-28
• ISBN (print): 9789464167245
• Sponsorship: Dutch Kidney Foundation; Dutch Heart Foundation; Eurolife; Leiden University Medical Center