Evaluation of the EMPAR study population on the basis of metabolic phenotypes of selected pharmacogenes

Abstract

The impact of genetic variability of pharmacogenes as a possible risk factor for adverse drug reactions is elucidated in the EMPAR (Einfluss metabolischer Profile auf die Arzneimitteltherapiesicherheit in der Routineversorgung/English: influence of metabolic profiles on the safety of drug therapy in routine care) study. EMPAR evaluates possible associations of pharmacogenetically predicted metabolic profiles relevant for the metabolism of frequently prescribed cardiovascular drugs. Based on a German study population of 10,748 participants providing access to healthcare claims data and DNA samples for pharmacogenetic assessment, first analyses were performed and evaluated. The aim of this first evaluation was the characterization of the study population with regard to general parameters such as age, gender, comorbidity, and polypharmacy at baseline (baseline year) as well as important combinations of cardiovascular drugs with relevant genetic variants and predicted metabolic phenotypes. The study was registered in the German Clinical Trials Register (DRKS) on July 6, 2018 (DRKS00013909).

Fig. 1. Recruitment scheme of the EMPAR study in 2018–2020.

Dropouts occurred in the provision of suitable DNA samples (11.1% in 2018–2019 and 13.1% in 2020), due to insufficient quality or a lack of genotype data (2.2%) and due to insufficient quality of healthcare claims data for matching (0.4%). PGx pharmacogenetic.

Fig. 2. Age and sex evaluation.

Age distributions of male and female participants in each study collective of the complete study population (anticoagulant: anticoagulant/antiplatelet collective, cholesterol reducer: cholesterol-lowering drug collective, Y-diagnosis: Y57.9! diagnosis collective) at baseline.

Fig. 3. Elixhauser comorbidity score distributions (in %).

All diagnosis codes (ICD-10) of the individual baseline year were taken into account. The score distribution reflects the comorbidity status of the complete study population in the baseline year grouped by age and gender.

Fig. 4. Abundance of concomitant medication prescribed during the individual baseline year grouped by age and collective.

Anticoagulant: anticoagulant/antiplatelet.

Fig. 5. Relevant actionable variants in the EMPAR population.

A Number of carriers of pharmacogenetic markers with PharmGKB Evidence level 1A/1B with regard to cardiovascular indications. Major allele here defined as wild type (W); M: minor allele or actionable variant respectively; NA: information not available; MW: actionable variant/wild type. B Proportions of participants in the complete study population with 1, 2, 3, 4, and ≥5 actionable variants shown in A.