Retrospective clinical and pharmacological audit of non-steroidal anti-inflammatory drug prescriptions and the "Triple Whammy" phenomenon in polymorbid outpatients

Background. The prescription of non-steroidal anti-inflammatory drugs (NSAIDs) in comorbid patients is associated with a high risk of adverse drug reactions (ADRs) and lack of therapeutic response. Of particular concern is the "Triple Whammy" — the combined use of systemic NSAIDs, renin-angiotensin-aldosterone system inhibitors (ACEIs/ARBs), and diuretics. To the best of our knowledge, this study is one of the first regional clinical pharmacological audits to quantitatively assess the prevalence of the "Triple Whammy" pattern specifically in outpatient practice, including an analysis of the quality of therapy documentation.

Objective. To evaluate the prescribing patterns of systemic NSAIDs and the frequency of potentially nephrotoxic drug combinations in polymorbid outpatients.

Materials and methods. A retrospective single-center study (n=50) was conducted. Demographic parameters, renal function (eGFR by CKD-EPI), concomitant pharmacotherapy, documented ADRs, and lack of therapeutic effect were assessed, with retrospective causality assessment using the WHO-UMC criteria. Statistical analysis was performed using non-parametric methods, calculating the odds ratio (OR) and 95 % confidence interval (CI).

Results. Signs of chronic kidney disease (CKD stages 3–5, eGFR < 60 mL/min/1.73 m² ) were identifi ed in 26 patients (52 %). A statistically significant association was found between reduced renal function and the prescribing frequency of the "Triple Whammy" combination (61.5 % vs. 12.5 %, p < 0.001). The odds ratio assessment (OR=11.2) confirms an increased risk; however, the wide confidence interval [95 % CI: 2.64–47.48] indicates the need for further refinement of the true effect size.

Conclusion. A high frequency of deficiencies in documenting safety parameters and a significant proportion of co-prescriptions of nephrotoxic combinations in patients with pre-existing renal impairment were identified. These findings highlight the need to implement automated pharmacovigilance algorithms at the outpatient level.

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