More on the “Triple Whammy”: antihypertensive drugs, non-steroidal anti-inflammatory agents and acute kidney injury – a case/non-case study in the French pharmacovigilance database

Abstract

It has been suggested that the risk of acute kidney injury (AKI) increases with the number of drugs associated between non-steroidal anti-inflammatory drugs (NSAIDs), angiotensin converting enzyme inhibitors (ACEis) [or angiotensin receptor blockers (ARBs)] and diuretics. We aimed to investigate whether the number of drugs associated between NSAIDs, ACEis, ARBs and diuretics was associated to disproportionate reporting of AKI in the French Pharmacovigilance Database. In reports of Adverse Drug Reactions (ADRs) recorded between 01 January 2008 and 31 December 2010, we selected patients whose medications included at least one oral antihypertensive drug. We used a case/non-case methodology. Cases were AKI and non-cases were all the remaining reports. Among the 11,442 ADR reports in patients under antihypertensive drug recorded in the French Pharmacovigilance Database, 837 ADRs were AKI (7.3%, 95% CI 6.8–7.8). AKI and the number of drugs associated were disproportionately reported (one drug alone: adjusted ROR 2.19, 95% CI: 1.65–2.89, two drugs: adjusted ROR 5.27, 95% CI: 4.00–6.94, three and more: adjusted ROR 16.46, 95% CI: 11.38–23.80). There was no significant association between NSAIDs’ half-lives and reporting of AKI (adjusted ROR = 0.54, 95% CI: 0.25–1.15). Given the widespread use of these hazardous drugs in general population, caution is needed when they are associated.