Atorvastatin treatment in patients with coronary heart disease – adherence and muscle side effects

Abstract

Statins represent a cornerstone in the pharmacological prevention of coronary heart disease. Although safe and effective, many patients do not adhere to their treatment, most commonly due to self-perceived muscle side effects. There is no consensus as to a definition of poor statin adherence, and valid measurement methods are lacking. Further, the causal relationship, if any, between statins and subjective muscle symptoms remains controversial. In this thesis, we have developed a novel direct method to measure adherence to atorvastatin, the most commonly used statin, based on blood concentrations of drug and metabolites. We then applied the method to show a strong relationship with blood cholesterol. We found that a majority of participants classified with reduced adherence by the new method did not respond correspondingly on self-report questionnaires. Last, the thesis studied the effect of atorvastatin on muscle symptoms in patients previously reporting subjective muscle symptoms presumed caused by the statin. Overall, we observed no effect on muscle symptom intensity and blood concentrations of atorvastatin and metabolites did not correlate to symptom intensity. In summary, the thesis provides a novel method to measure adherence to atorvastatin and new knowledge on muscle side effects in patients with coronary heart disease. This may allow future individual tailoring of statin treatment to optimize effect and improve clinical outcomes.