University affiliation
Uppsala University
Main supervisor
Johan Sundström, Profesor of Epidemiology
PhD project participating in the National Research School in General Medicine.
Treatment with blood-pressure lowering drugs is one of the most important actions for the prevention of cardiovascular disease and premature death. Unfortunately, despite accessible and cheap medication adherence is generally low. We plan to analyze large volumes of health-care data and have performed a randomized trial to determine if the right choice of blood-pressure lowering drug can better adherence and minimize adverse events.
Hypertension is the leading cause of premature death and disability in the world (1) and the prevalence in estimated to be around 30% in adults (2) (3). Sadly, studies show a general low adherence to blood pressure-lowering drugs and only one out of two patients are estimated to be adherent to prescribed therapy (4).
In the latest European guidelines four classes of blood-pressure-lowering drugs are given equal footing of recommendation for the treatment of uncomplicated hypertension when treated in monotherapy (5). However, adherence in real-life might differ between the drug-classes because of differences in side-effects and blood-pressure responses inherent to the different drug-classes.
The overall aim of this thesis is to investigate if there are differences in adherence and cardiovascular outcome between the recommended classes of blood-pressure lowering drugs when compered in real-life and if this could be explained by differences in side-effects.
Sample 1: AMCA - Adherence to the Major Classes of Antihypertensive therapy
A register based nation-wide cohort of all individuals initiating a blood pressure-lowering drug in single pill therapy between 2011 and 2018 with one or more of the recommended classes for the treatment of uncomplicated hypertension have been created by cross referencing the Swedish national prescription registers with three other Swedish national registers. Primary outcomes will be adherence to therapy and first cardiovascular event. Secondary analysis will be done to investigate if any differences in cardiovascular outcome are mediated by differences in adherence.
Sample 2: PHYSIC -The Precision Hypertension Care Study
Between April 2017 and June 2021, 280 patients were included in a double-blind randomized, repeated cross-over, single center study at Uppsala University Hospital(6). The participants were given the four recommended classes of blood pressure drugs consecutively with intermediary wash out periods, and two of the classes were also given repeatedly. For my thesis I will explore differences in side effects and if 24 h blood-pressure patterns are affected by adherence. I will also investigate if the side-effects are persistent between treatment periods when the participant receives the same blood-pressure lowering drug a second time.
If adherences differ between the recommended classes of antihypertensives to a clinically meaningful degree, this suggests that the equal footing of recommendation of these drug classes issued by the ESC could be questioned. Further, this knowledge could offer a cost-effective and easy way to increase adherence to treatment of a condition affecting billions. If the PHYSIC study displays a pattern of side-effects corresponding to the adherence results in the AMCA study, this could suggest a causal pathway and strengthen the results of the latter. Further it is possible that different classes of blood pressure-lowering drugs lead to better adherence in different individuals or groups of individuals. An important aspect of the PHISIC study is to determine if side effects and blood pressure responses are persistent when given the drug a second time to the same individual. If this is true, this is an important step towards the future development of precision medicine.
Uppsala University
Johan Sundström, Profesor of Epidemiology