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Xuechun Li,1 Dennis Steenhuis,1 Maarten J Bijlsma,1,2 Stijn de Vos,1 Sumaira Mubarik,1 Jens HJ Bos,1 Catharina CM Schuiling-Veninga,1 Eelko Hak1 1Pharmacotherapy, Epidemiology and Economics, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, the Netherlands; 2Laboratory of Population Health, Max Planck Institute for Demographic Research, Rostock, GermanyCorrespondence: Xuechun Li, PhD Research Fellow, Pharmacotherapy, Epidemiology and Economics, Groningen Research Institute of Pharmacy, University of Groningen, 9713 AV Groningen, the Netherlands, Tel +31 649019602, Email xuechen.li@rug.nlPurpose: Anti-hyperlipidemic drug treatments are effective in reducing the risk of cardiovascular disease. In a long-term retrospective inception cohort study, we aimed to assess the real-world comparative effectiveness of anti-hyperlipidemic monotherapies for primary prevention of cardiovascular events.Patients and Methods: Patients aged 18 years and older, who initiated primary prevention with anti-hyperlipidemic monotherapy, were selected from the University of Groningen IADB.nl dispensing database. In intention-to-treat (ITT) analysis we included all patients, whereas in per-protocol (PP) analysis we included both all patients independent of adherence (PPIA) and adherent patients (PPA). Study outcome was the time to first prescription of acute cardiac drug therapy measured by valid drug proxies to identify a first major cardiovascular event. We applied inverse probability of treatment-weighted (IPTW) analysis using Cox regression and time-varying Cox regression with simvastatin as the reference category to estimate the average treatment effect hazard ratios (HR) and their corresponding 95% confidence intervals (CI).Results: Atorvastatin users had significantly higher hazards compared to simvastatin users (HR range: 1.27 to 1.47, 95% CI: 1.15 to 1.69). Similarly, Pravastatin users also exhibited increased hazards compared to simvastatin users (HR range: 1.41 to 1.56, 95% CI: 1.14 to 2.04). Similar patterns were observed in patients with diabetes, rheumatoid arthritis, and asthma/COPD. No differences were found in the hazards of rosuvastatin, fluvastatin, fibrates, and simvastatin.Conclusion: Atorvastatin and pravastatin users had higher long-term rates of cardiovascular events compared to simvastatin monotherapy in primary prevention, the difference may be attributed to the confounding by severity, but also possibly due to differences in drug mechanisms or patient response. These findings could influence current guideline recommendations, suggesting a potential preference for simvastatin in primary prevention, underscoring the need for further research to explore long-term impacts and underlying mechanisms, especially in diverse populations. Keywords: acute cardiac drug therapy, time-varying confounding, inverse probability treatment weighting, Cox regression

Irene Mommers,1 Job FM van Boven,2,3 Catharina CM Schuiling-Veninga,1 Jens HJ Bos,1 Marten Koetsier,1 Eelko Hak,1 Maarten J Bijlsma1,4 1Pharmacotherapy, Epidemiology and -Economics, University of Groningen, Groningen, the Netherlands; 2Groningen Research Institute for Asthma and COPD, University Medical Center Groningen, Groningen, the Netherlands; 3Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, Groningen, the Netherlands; 4Laboratory of Population Health, Max Planck Institute for Demographic Research, Rostock, GermanyCorrespondence: Irene Mommers, University of Groningen, Department of Pharmacotherapy, -Epidemiology and -Economics, Antonius Deusinglaan 1, Building 3214, Room 0450, Groningen, 9713 AV, the Netherlands, Tel +31 50 36 32476, Email i.mommers@rug.nlPurpose: The Global Initiative for Asthma (GINA) suggests a step-wise approach for pharmacological treatment of asthma. Valid study of real-world treatment patterns using dispensing databases includes proper measurement of medication adherence. We aim to explore such patterns by applying a time-varying proportion of days covered (tPDC)-based algorithm.Patients and Methods: We designed a retrospective inception cohort study using the University of Groningen IADB.nl community pharmacy dispensing database. Included were 19,184 young adults who initiated asthma medication anywhere between 1994 and 2021, in the Netherlands. Main treatment steps were defined as: 1 - SABA/ICS-formoterol as needed, 2 - low dose ICS, 3 - low dose ICS + LABA or tiotropium, or intermediate dose ICS, 4 - intermediate to high dose ICS + LABA or tiotropium, triple therapy, or high dose ICS, 5 - treatment prescribed by a specialist. Changes in treatment steps were determined using a time-varying proportion of days covered (tPDC)-based algorithm. Individual drug treatment trajectories were visualized over time using a lasagna plot.Results: At initiation, of the 19,184 included individuals, 52%, 7%, 15%, 16%, and 10% started treatment in steps 1 to 5, respectively. The median (IQR) follow-up time was 3 (1– 7) years. Median (IQR) number of switches was 1 (0– 3). Comparing starting step to last observed step, 37% never switched between treatment steps, 20% of individuals stepped down and 22% stepped up.Conclusion: The low proportion of treatment switches between steps indicates that tailoring of treatment to patients’ needs might be suboptimal. The tPDC-based algorithm functions well in translating dispensing data into continuous drug-utilization data, enabling a more granular assessment of treatment patterns among asthma patients.Keywords: asthma management, respiratory disease, inhaler medication, personalized medicine, longitudinal, observational

Bianca Mulder,1 Maarten J Bijlsma,1 Catharina CM Schuiling-Veninga,1 Leonard P Morssink,2 Eugene van Puijenbroek,3,4 Jan G Aarnoudse,5 Eelko Hak,1 Tjalling W de Vries6 1Groningen Research Institute of Pharmacy, Unit PharmacoTherapy, Epidemiology & Economics, University of Groningen, Groningen, the Netherlands; 2Department of Obstetrics and Gynaecology, Medical Center Leeuwarden, Leeuwarden, the Netherlands; 3Netherlands Pharmacovigilance Centre Lareb, ´s-Hertogenbosch, the Netherlands; 4Unit of Pharmacotherapy and Pharmaceutical Care, Department of Pharmacy, University of Groningen, Groningen, the Netherlands; 5Department of Obstetrics and Gynaecology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; 6Department of Pediatrics, Medical Center Leeuwarden, Leeuwarden, the Netherlands Background: Understanding perception of risks and benefits is essential for informed patient choices regarding medical care. The primary aim of this study was to evaluate the perception of risks and benefits of 9 drug classes during pregnancy and associations with women’s characteristics.Methods: Questionnaires were distributed to pregnant women who attended a Dutch Obstetric Care facility (first- and second-line care). Mean perceived risk and benefit scores were computed for 9 different drug classes (paracetamol, antacids, antibiotics, antifungal medication, drugs against nausea and vomiting, histamine-2 receptor antagonists/proton pump inhibitors, antidepressants, nonsteroidal anti-inflammatory drugs, and sedatives/anxiolytics). For each participant, we computed weighted risk and benefit sum scores with principal component analysis. In addition, major concerns regarding medication use were evaluated.Results: The questionnaire was completed by 136 women (response rate 77%). Pregnant women were most concerned about having a child with a birth defect (35%), a miscarriage (35%), or their child developing an allergic disease (23%), respectively, as a result of drug use. The majority of studied drug classes were perceived relatively low in risk and high in benefit. Higher risk scores were reported if women were in their first trimesters of pregnancy (p=0.007). Lower benefit scores were reported if women were single (p=0.014), smoking (p=0.028), nulliparous (p=0.006), or did not have a family history of birth defects (p=0.005).Conclusion: Pregnant women’s concerns regarding potential drug adverse effects were not only focused on congenital birth defects but also included a wider range of adverse outcomes. This study showed that most of the studied drug classes were perceived relatively low in risk and high in benefit. Keywords: drugs, perception, risks, benefits, worries, pregnancy