Retrospective Nation-Wide Cohort Study on the Combined Prescription of Simvastatin and Amlodipine and Its Adverse Effects: Amlostatina Study Protocol

Objective: There is a possible interaction of clinical relevance with the prescription of simvastatin 40 mg with amlodipine. Amlodipine would interact by increasing the concentration of simvastatin, which could induce potentially serious adverse effects. This combination prescription generates safety alerts in our electronic clinical prescription system that often involve a statin change. However, the literature that supports this alert is not numerous and is of low quality. Our objective is to evaluate the combined prescription of simvastatin and amlodipine in Catalonia and its adverse effects with respect to the combination of atorvastatin and amlodipine. Design and method: It is a retrospective cohort study that includes individuals registered in the System for the Development of Research in Primary Care. This is a valid and reliable database that contains longitudinal health records of around 6 million people (80% of national population). Patients included are those who have received a joint prescription of simvastatin or atorvastatin and amlodipine at any dose between 2007 and the present Patients who have had pathologies that could be considered adverse effects prior to prescription will be excluded. The main outcome variable is adverse effects occurring after the prescription of the statin-amlodipine combination A multivariate analysis will be performed with all possible confounding factors and the risk of side effects will be calculated through a logistic regression model. The risks will be described using OR and RR with their 95% confidence intervals between the combination of simvastatin/amlodipine and the combination of other statins with amlodipine. Possible confounding factors such as sex, age, duration of treatment, dosage of the drugs and history of previous comorbidities such as the existence of CKD or the use of other drugs that may increase the toxic potential of the combination will be assessed In all cases, a p<0.05 is considered as a statistical significance Results: It is expected to see that the risk of adverse effects of simvastatin amlodipine is low and little different from that of atorvastatin, and those produced are of little clinical relevance. Conclusions: It is important because it could lead to more cost-efficient prescribing patterns.