Aims To assess the gabapentinoid–oedema–loop diuretic prescribing cascade in adults using large administrative health care databases from the USA and Denmark. Methods This study used a sequence symmetry analysis to assess loop diuretic initiation before and after the initiation of gabapentinoids among patients aged 20 years or older without heart failure or chronic kidney disease. Data from MarketScan Commercial and Medicare Supplemental Claims databases (2005 to 2019) and Danish National Prescription Register (2005 to 2018) were analyzed. Use of loop diuretics associated with initiation of selective norepinephrine reuptake inhibitors (SNRI) was used as a negative control. We assessed the pooled temporality of loop diuretic initiation relative to gabapentinoid or SNRI initiation across the 2 countries. Secular trend‐adjusted sequence ratios (aSRs) with 95% confidence intervals (CIs) were calculated using data from 90 days before and after initiation of gabapentinoids. Pooled ratio of aSRs were calculated by comparing gabapentinoids to SNRIs. Results Among the 1 511 493 gabapentinoid initiators (Denmark [n = 338 941]; USA [n = 1 172 552]), 20 139 patients had a new loop diuretic prescription 90 days before or after gabapentinoid initiation, resulting in a pooled aSR of 1.33 (95% CI 1.06–1.67). The pooled aSR for the negative control (i.e., SNRI) was 0.84 (95% CI 0.75–0.94), which resulted in a pooled ratio of aSRs of 1.58 (95% CI 1.23–2.04). Pooled estimated incidence of the gabapentinoid–loop diuretic prescribing cascade was 8.14 (95% CI, 1.92–34.49) events per 1000 patient‐years. Conclusion We identified evidence of the gabapentinoid–oedema–loop diuretic prescribing cascade in 2 countries.

Background The use of a new medication (e.g., potassium supplementation) for managing a drug‐induced adverse event (e.g., loop diuretic‐induced hypokalemia) constitutes a prescribing cascade. However, loop diuretics are often stopped while potassium may be unnecessarily continued (i.e., relic). We aimed to quantify the occurrence of relics using older adults previously experiencing a loop diuretic‐potassium prescribing cascade as an example. Methods We conducted a prescription sequence symmetry analysis using the population‐based Medicare Fee‐For‐Service data (2011–2018) and partitioned the 150 days following potassium initiation by day to assess the daily treatment scenarios (i.e., loop diuretics alone, potassium alone, combination of loop diuretics and potassium, or neither). We calculated the proportion of patients developing the relic, proportion of person‐days under potassium alone, the daily probability of the relic, and the proportion of patients filling potassium after loop diuretic discontinuation. We also identified the risk factors of the relic. Results We identified 284,369 loop diuretic initiators who were 8 times more likely to receive potassium supplementation simultaneously or after (i.e., the prescribing cascade), rather than before, loop diuretic initiation (aSR 8.0, 95% CI 7.9–8.2). Among the 66,451 loop diuretic initiators who subsequently (≤30 days) initiated potassium, 20,445 (30.8%) patients remained on potassium after loop diuretic discontinuation, and 9365 (14.1%) patients subsequently filled another potassium supplementation. Following loop diuretic initiation, 4.0% of person‐days were for potassium alone, and daily probability of the relic was the highest after day 90 of loop diuretic initiation (5.6%). Older age, female sex, higher diuretic daily dose, and greater baseline comorbidities were risk factors for the relic, while patients having the same prescriber or pharmacy involved in the use of both medications were less likely to experience the relic. Conclusions Our findings suggest the need for clinicians to be aware of the potential of relic to avoid unnecessary drug use.

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