Hospitalisations Related to the Combination of ACE Inhibitors and/or Angiotensin Receptor Blockers with Diuretics and NSAIDs: A Post Hoc Analysis on the Risks Associated with Triple Whammy

Irene Mattioli; Alessandra Bettiol; Giada Crescioli; Roberto Bonaiuti; Guido Mannaioni; Alfredo Vannacci; Niccolò Lombardi; MEREAFaPS Study Group

doi:10.3390/healthcare11020238

Hospitalisations Related to the Combination of ACE Inhibitors and/or Angiotensin Receptor Blockers with Diuretics and NSAIDs: A Post Hoc Analysis on the Risks Associated with Triple Whammy

Healthcare (Basel). 2023 Jan 12;11(2):238. doi: 10.3390/healthcare11020238.

Authors

Irene Mattioli¹, Alessandra Bettiol¹, Giada Crescioli^{2

3}, Roberto Bonaiuti^{2

3}, Guido Mannaioni⁴, Alfredo Vannacci^{2

3}, Niccolò Lombardi^{2

3}; MEREAFaPS Study Group

Affiliations

¹ Department of Experimental and Clinical Medicine, University of Florence, 50139 Florence, Italy.
² Department of Neurosciences, Psychology, Drug Research and Child Health, Section of Pharmacology and Toxicology, University of Florence, 50139 Florence, Italy.
³ Tuscan Regional Centre of Pharmacovigilance, 50139 Florence, Italy.
⁴ Toxicology Unit, Poison Control Center, Careggi University Hospital, 50139 Florence, Italy.

Abstract

This post hoc analysis aimed to assess and characterise adverse events (AEs) related to the triple whammy (i.e., combination therapy of ACE inhibitors, ACE-I, and/or angiotensin receptor blockers, ARBs, with diuretics and non-steroidal anti-inflammatory drugs, NSAIDs) leading to emergency department (ED) visits and/or hospitalisations in the Italian setting. The MEREAFaPS database was analysed. ED visits related to co-treatment with ACE-I and/or ARBs, diuretics, and NSAIDs were considered. Information on the AE (including classification, seriousness, and outcome), suspected and concomitant drugs, and concomitant conditions was retrieved and analysed. Logistic regression was used to estimate the reporting odds ratios (RORs) of hospitalisation associated with the drugs of interest. Between 1 January 2007, and 31 December 2018, 80 patients visited the ED for AEs related to the triple whammy, and a total of 261 suspected drugs were involved. Patients were mostly Caucasian females, with a median age of 85 years, and only 9 of them had renal manifestations. In this subset, drug-drug interaction contributed to kidney injury. Most patients presented a Charlson comorbidity index of 4-5. Overall, 47 patients were hospitalised (58.75%), but no significant differences in the risk of hospitalisation were found according to demographic, clinical, or therapeutic features.

Keywords: ACE inhibitors; adverse drug reactions; angiotensin-II-receptor antagonists; diuretics; drug safety; hospitalisations; nonsteroidal anti-inflammatory drugs; pharmacovigilance; renal kidney injury; triple whammy.

Grants and funding

This study was funded by a research grant from the AIFA (the Italian Medicines Agency), Rome, Italy, Tuscan County resolution DGRT 790/2016 All. C. The founder of the study had no role in the collection, analysis, and interpretation of data, nor in the writing of the report, nor in the decision to submit the article for publication.