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Keywords = triple whammy

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13 pages, 1366 KB  
Article
Frequency and Profiles of Drug Combinations Constituting the Triple Whammy in Japan: An Analysis of a Patient Estimation Database
by Mari Maese, Nozomi Ito, Haruka Shiokawa, Shingo Kondo, Yuko Okamoto, Hiroki Iwata, Shunsuke Urushibata and Katsunori Yamaura
Pharmacy 2026, 14(5), 117; https://doi.org/10.3390/pharmacy14050117 - 8 Aug 2026
Viewed by 201
Abstract
“Triple whammy” prescriptions, combining non-steroidal anti-inflammatory drugs (NSAIDs), renin–angiotensin system (RAS) inhibitors, and diuretics, increase acute kidney injury (AKI) risk. To clarify the frequency and profiles of these prescriptions and identify vulnerable populations, we analyzed the AHI partners database to estimate the number [...] Read more.
“Triple whammy” prescriptions, combining non-steroidal anti-inflammatory drugs (NSAIDs), renin–angiotensin system (RAS) inhibitors, and diuretics, increase acute kidney injury (AKI) risk. To clarify the frequency and profiles of these prescriptions and identify vulnerable populations, we analyzed the AHI partners database to estimate the number of individuals prescribed these three drug classes. In the single-agent analysis, loxoprofen was the most commonly prescribed NSAID (66.3%), olmesartan (19.4%) and telmisartan (15.9%) were the predominant RAS inhibitors, and furosemide (19.6%) and spironolactone (16.0%) were the most frequently used diuretics. Dual-drug combinations showed patterns consistent with the single-agent results for NSAIDs and diuretics. By contrast, sacubitril/valsartan was the most common RAS inhibitor when combined with diuretics, frequently utilized for heart failure management. In triple whammy prescriptions, NSAIDs and diuretics patterns mirrored those of single-agents. The annual number of triple whammy prescriptions showed a statistically significant downward trend over the study period by the Mann–Kendall trend test (p = 0.048). Notably, sacubitril/valsartan was the leading RAS inhibitor (46/199 patients, 23%), showing a higher proportion than its single-agent use (7.4%). Heart failure patients prescribed these two causative drugs are highly vulnerable to “triple whammy” prescriptions. Awareness of inadvertent NSAID additions is warranted to mitigate potential AKI risks. Full article
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13 pages, 230 KB  
Article
Does Metamizole Cause Less Acute Kidney Injury than Non-Steroidal Anti-Inflammatory Drugs When Combined with Diuretics and Antihypertensives?
by Dulce Maria Calvo, Luis Carlos Saiz, Leire Leache, Maria C. Celaya, Marta Gutiérrez-Valencia, Alvaro Alonso and Juan Erviti
Toxics 2025, 13(5), 417; https://doi.org/10.3390/toxics13050417 - 21 May 2025
Cited by 1 | Viewed by 8845
Abstract
The concurrent use of (a) diuretics, (b) renin–angiotensin–aldosterone system inhibitors (RAASIs), and (c) non-steroidal anti-inflammatory drugs (NSAIDs) or metamizole, known as the triple whammy (TW) combination, increases the risk of acute kidney injury (AKI). This study compared TWs including metamizole versus NSAIDs regarding [...] Read more.
The concurrent use of (a) diuretics, (b) renin–angiotensin–aldosterone system inhibitors (RAASIs), and (c) non-steroidal anti-inflammatory drugs (NSAIDs) or metamizole, known as the triple whammy (TW) combination, increases the risk of acute kidney injury (AKI). This study compared TWs including metamizole versus NSAIDs regarding hospitalisation for AKI, need for renal replacement therapy (RRT), and all-cause mortality during hospitalisation. Serum creatinine (sCr) and estimated glomerular filtration rate (eGFR) changes in the first year after TW initiation were also assessed. A nested case–control study was conducted within a cohort of adults receiving TW therapy (2009–2018). Logistic regression models analysed the associations between TW type and outcomes. Among 65,077 individuals (mean age 79.7 years; 26.3% male), TW including an NSAID was associated with a lower risk of AKI-related hospitalisation [adjusted odds ratio (aOR) 0.81, 95%CI 0.74–0.87] and all-cause mortality (aOR 0.64, 95%CI 0.49–0.82) compared to TW including metamizole. No significant differences were found in other variables. These findings suggest that TW including an NSAID may reduce the risk of AKI-related hospitalisation and mortality compared to TW including metamizole, although kidney function parameters remained unaffected. Further research is needed to confirm these results. Full article
(This article belongs to the Special Issue Nephrotoxicity Induced by Drugs and Chemicals in the Environment)
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13 pages, 267 KB  
Article
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
by Irene Mattioli, Alessandra Bettiol, Giada Crescioli, Roberto Bonaiuti, Guido Mannaioni, Alfredo Vannacci and Niccolò Lombardi
Healthcare 2023, 11(2), 238; https://doi.org/10.3390/healthcare11020238 - 12 Jan 2023
Cited by 4 | Viewed by 11413
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Pharmacovigilance and Appropriate Drug Use)
2 pages, 330 KB  
Case Report
Hemoptysis with Lung Cavity—Triple Whammy
by Vidushi Rathi and Pranav Ish
Adv. Respir. Med. 2020, 88(1), 35-36; https://doi.org/10.5603/ARM.a2020.0078 - 20 Feb 2020
Cited by 2 | Viewed by 924
Abstract
A 37-year male presented with cough and dyspnoea for 9 months that had worsened over the past 7 days and was complicated by haemoptysis [...] Full article
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