Statins, a class of cholesterol-lowering drugs, have gained increasing popularity for the treatment of high cholesterol levels with the aim to reduce the risk of heart disease and early death. While clinical trials have pointed towards the potential beneficial effects of statin therapy, they may not be fully able to capture real life effects occurring during routine care. Moreover, many clinical trials lack the long-run perspective necessary to critically evaluate the benefits and potential risks of statin-based treatment. At the same time, studies that do not conduct experiments can take advantage of real-life clinical data but are often not able to establish causality because many factors that are not controlled by the researcher may influence the results. To avoid both problems, this study makes use of large electronic patient records and focusses on treatment decisions based on major clinical guidelines in the UK in order to test the real-life effectiveness of statin therapy. Thanks to the large number of patients included in CPRD and the extensive time horizon during which these patients were observed, we are not only able to study immediate benefits but also long-run survival advantages and potential adverse effects for various groups of patients. Given the widespread use of statin therapy, the results of this study have direct implications for clinical care.
Previous studies investigating the health effects of statin therapy administered to patients with high cholesterol levels are largely limited to controlled clinical trials. While these studies have pointed towards the efficacy of statin therapy in improving key health outcomes, they might not be able to fully capture treatment effectiveness during routine care and frequently lack the necessary time horizon to study long-run benefits and risks. Non-experimental studies, in contrast, may fail to establish causality due to insufficient control of confounding factors. This study seeks to measure the effect of statin therapy on short-, mid-, and long-term clinical outcomes (mortality, hospitalizations, major adverse health events) in a routine care set-up for adult men and adult women of various age groups. To establish causality, we make use of a regression discontinuity (RD) design taking advantage of major UK clinical guidelines recommending statin therapy based on threshold rules related to patients cardiovascular disease (CVD) risk scores. Because physicians base their treatment decisions on additional considerations besides CVD risk, we use an instrumental variable approach that is robust to partial compliance. We evaluate the robustness of results by gradually narrowing down the bandwidth around the treatment threshold and thus only including patients with CVD risk scores increasingly close to the treatment threshold level. The findings of this study are expected to provide novel insights into the effectiveness of statin therapy in a real-life setting and can directly inform clinical practice.
Primary outcomes (all to be measured over time horizons of one year, five years, ten years, and 15 years): number of all-cause emergency hospitalizations; number of severe adverse health events (stroke, heart attack, type 2 diabetes, rhabdomyolysis, autoimmune myopathy, dementia each event type evaluated separately); all-cause mortality
Secondary outcomes (all to be measured over time horizons of one year, five years, ten years, and 15 years): probability of at least one all-cause emergency hospitalization; number of all-cause hospitalizations; probability of at least one all-cause hospitalization; number of hospitalizations due to heart attacks and strokes; probability of at least one hospitalization due to heart attack or stroke; probability of at least one severe adverse health event (as listed under primary outcomes); mortality due to stroke or heart attack; potential side effects of statins (explorative, in addition to the adverse events listed under primary outcomes)
Till Bärnighausen - Chief Investigator - University of Heidelberg
Christian Bommer - Corresponding Applicant - University of Heidelberg
Anant Jani - Collaborator - University of Oxford
Duy Do - Collaborator - University of Heidelberg
Julia Lemp - Collaborator - University of Heidelberg
Justine Davies - Collaborator - University of Birmingham
Michaela Theilmann - Collaborator - University of Heidelberg
Pascal Geldsetzer - Collaborator - University of Heidelberg
Sebastian Vollmer - Collaborator - Georg-August-Universität Göttingen
2011 Rural-Urban Classification at LSOA level;HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation