Pharmacy

Thi Ngoc Mai Nguyen, Pharmacist
Netzwerk AlternsfoRschung (NAR)
Bergheimer Straße 20
D-69115 Heidelberg

Phone: +49 (0)6221 54 8143
nguyen(at)nar.uni-heidelberg.de
Fellow: Ben Schöttker, PhD

 

Non-steroidal anti-inflammatory drugs: the epidemiology of their utilisation in the older German population and new insights into the risks and benefits of low-dose acetylsalicylic acid use

Summary of PhD thesis

Chronic pain is frequent in older people, challenging to manage and interferes significantly with the daily life of people affected. However, comprehensive studies on analgesic utilization in this age group from Germany are scarce. Furthermore, although accounting for over 50% of the prescribed analgesics in Europe, non-steroidal anti-inflammatory drugs (NSAIDs) present a negative risk-benefit profile in adults aged ≥ 65 years.

In the first part of this dissertation, I conducted a drug utilization study and gave a comprehensive overview of the use of the most common therapeutic groups of analgesics in community-dwelling older adults from Germany, followed by comparing the prevalence of potentially inappropriate medication (PIM) among NSAIDs users and identifying the determinants of their use. In detail, a cross-sectional study was carried out using data from 2,038 community-dwelling adults aged 63–89 years of the ESTHER cohort study. The results showed that one out of four study participants was suffering from high-intensity or disabling pain, and half of those taking analgesics still reported suffering from high-intensity or disabling pain. Among analgesics users, occasional NSAIDs use was the most frequent pain therapy (in 43.6% of users), followed by metamizole use (16.1%), regular NSAIDs use (12.9%), strong opioids use (12.7%), and weak opioids use (12.0%). In multivariate logistic regression models, higher age, higher pain severity, longer pain duration, abdominal pain, and back pain were statistically significantly associated with opioid use. Metamizole use was also statistically significantly associated with higher pain severity but inversely associated with pain duration.

Prevalence of potentially inappropriate NSAIDs use was 54.2%, 45.4%, 29.9%, 20.4%, and 3.5% when applying the STOPP, 2019 Beers, EU(7)-PIM, FORTA, and PRISCUS PIM criteria, respectively. Only the STOPP and Beers criteria showed a moderate inter-instrument agreement. Lower pain severity, gout, peptic ulcer, cardiovascular disease, and chronic kidney disease were statistically significantly associated with potentially inappropriate NSAIDs use defined by the STOPP criteria and the latter three conditions also with the 2019 Beers criteria.

In conclusion, a significant number of older German adults are affected by high-intensity and disabling chronic pain despite receiving analgesics. The STOPP and Beers criteria might be superior to other PIM lists in identifying potentially inappropriate NSAIDs use. I developed a harmonized, country-independent PIM list for NSAIDs with the same advantages as observed for the STOPP and 2019 Beers criteria and recommended its application in routine clinical practice.

In the second part of the thesis, I focused on risks (for gastric and duodenal ulcer) and benefits (dementia prevention) of long-term low-dose acetylsalicylic acid (LDASA) use. Due to the lack of effective dementia treatments, prevention still plays a crucial role. There have been hints suggesting a neuroprotective effect of LDASA, but the evidence was inconclusive. Thus, I investigated the potential protective effect of long-term LDASA use with all-cause dementia, Alzheimer's disease and vascular dementia incidence in a sample of 5,258 participants from the ESTHER study and 305,394 participants from the UK Biobank. Cox regression models with inverse probability of treatment weighting were used to model the underlying cardiovascular risk. The meta-analysis of both cohorts revealed a weak reduction in hazards for all-cause dementia. However, the strongest association of LDASA was observed in participants with coronary heart disease. In particular, a 31% risk reduction for Alzheimer’s disease, 69% for vascular dementia and 34% for all-cause dementia were shown in the meta-analysis of the two cohorts. Furthermore, compared to non-use, the use of LDASA for 10 years or longer was strongly inversely associated with all dementia outcomes.

The ESTHER study (N=7,737) and the UK Biobank (N=213,598) were also used to address the association of LDASA use with gastric and duodenal ulcer incidence using multivariate Cox regression models. In the prevalent user design, no significant association was found with gastric ulcers in both cohorts. Furthermore, LDASA use was only weakly associated with duodenal ulcers in the UK Biobank and ESTHER study with 30% and 26% excess risks, respectively. When restricting the exposure to only new users, results were much stronger. In the UK Biobank and ESTHER, the hazard ratio point estimates for gastric ulcer were 1.98 and 2.73, respectively, and for duodenal ulcer 1.81 and 3.69, respectively.

The second part of the dissertation has demonstrated a protective potential of LDASA use against dementia in patients with pre-existing coronary heart disease and those willing to take it for a minimum of ten years. At the same time, it showed that initiation of long-term LDASA therapy increases the risk of developing gastric and duodenal ulcers substantially. Taken together, it is essential to weigh risks against benefits when LDASA treatment shall be initiated and to monitor adverse gastrointestinal symptoms after the start of LDASA therapy. Especially for subjects with coronary heart disease, the benefit of dementia prevention should be taken into account in the benefit-risk balance of the drug, in addition to LDASA’s well-known benefits in the prevention of major cardiovascular events.

 

 

Publications

  • Nguyen, T. N. M., Laetsch DC, Chen LJ, Holleczek B, Meid AD, Brenner H, Schöttker B. Comparison of Five Lists to Identify Potentially Inappropriate Use of Non-Steroidal Anti-inflammatory Drugs in Older Adults. Pain Med. 2021;22(9):1962-1969.
  • Nguyen, T. N. M., Laetsch DC, Chen LJ, Haefeli WE, Meid AD, Brenner H, Schöttker B. Pain severity and analgesics use in the community-dwelling older population: a drug utilization study from Germany. Eur J Clin Pharmacol. 2020;76(12):1695-1707
  • Nguyen, T. N. M., Chen, L. J., Trares, K., Stocker, H., Holleczek, B., Beyreuther, K., Brenner, H., & Schöttker, B. Longitudinal associations of low-dose acetylsalicylic acid use with all-cause and vascular dementia and Alzheimer’s disease in the general population. 2022. [Submitted]; Pre-print: https://www.medrxiv.org/content/10.1101/2021.09.20.21263830v1
  • Nguyen, T. N. M., Chen, L. J., Holleczek, B., Brenner, H., & Schöttker, B. Low-dose acetylsalicylic acid use is associated with increased risk of gastric and duodenal ulcers: Results from two large cohorts with new-user design. 2022 [Submitted]

Vita

02/2019-01/2022 PhD Student, Network Aging Research (NAR), University of Heidelberg
2016-2018 Master of Public Health, University of Tsukuba, Japan
2015-2016 Pharmacist, University Medical Center, Ho Chi Minh, Vietnam
2010-2015 Studies of Pharmacy, University of Medicine and Pharmacy, Ho Chi Minh, Vietnam

 

 

 

 

 

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Latest Revision: 2022-02-14
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