Risk of Nephrotic Syndrome for Non-Steroidal Anti-Inflammatory Drug Users.

BACKGROUND AND OBJECTIVES: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with AKI. Their association with nephrotic syndrome has not been systematically studied. This study aimed to assess the risk of nephrotic syndrome associated with NSAID use. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A matched case-control study was performed in the UK primary care database. Cases were patients with a first diagnosis of nephrotic syndrome and controls were those without nephrotic syndrome. NSAID exposure (grouped either based on cyclooxygenase enzyme selectivity and chemical groups) was classified as either current (use at the nephrotic syndrome diagnosis date and corresponding date in the control group), recent, or past use. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using unconditional logistic regression analysis. RESULTS: We included 2620 cases and 10,454 controls. Compared with non-use, current use of 15-28 days and >28 days of conventional NSAIDs was associated with a higher relative risk of nephrotic syndrome: adjusted OR, 1.34; 95% CI, 1.06 to 1.70, and OR, 1.42; 95% CI, 0.79 to 2.55, respectively. Also, recent use (discontinuation 1-2 months before nephrotic syndrome diagnosis date; OR, 1.55; 95% CI, 1.11 to 2.15) and past use (discontinuation 2 months-2 years; OR, 1.24; 95% CI, 1.07 to 1.43), but not current use of <15 days (OR, 0.78; 95% CI, 0.46 to 1.31) nor past use (discontinuation >2 years; OR, 0.96; 95% CI, 0.85 to 1.09) were associated with a higher relative risk of nephrotic syndrome as well as past use of selective COX-2 inhibitors (discontinuation 2-24 months; OR, 1.24; 95% CI, 0.98 to 1.58). Categorization based on chemical groups showed that acetic acid and propionic acid derivatives were associated with a higher risk of nephrotic syndrome. CONCLUSIONS: The use of conventional NSAIDs was associated with a higher risk of nephrotic syndrome starting from at least 2 weeks of exposure, as well as for recent and past exposure up to 2 years before the diagnosis of nephrotic syndrome. This higher risk appeared mainly attributable to acetic acid and propionic acid derivatives.

Risk of myocardial infarction associated with non-steroidal anti-inflammatory drugs: Impact of additional confounding control for variables collected from self-reported data.

WHAT IS KNOWN AND OBJECTIVE: Important risk factors and over-the-counter (OTC) dispensing of non-steroidal anti-inflammatory drugs (NSAIDs) are often not routinely recorded in electronic health records. This study aimed to assess the impact of patient's reports on these factors on the risk of acute myocardial infarction (AMI) for NSAID use. METHODS: A nested case-control study was conducted among adults in the Utrecht Cardiovascular Pharmacogenetics study. Cases were patients with a first diagnosis of AMI as a hospital discharge diagnosis and controls were those without AMI. NSAID exposure was either current use of selective COX-2 inhibitors or conventional NSAIDs. Information was collected from The Dutch PHARMO Database Network (pharmacy records of drug dispensing linked to hospitalization records) and the patient's questionnaire (lifestyle factors, body mass index and history of cardiovascular diseases). Unconditional logistic regression analysis was used to calculate odds ratios (ORs) and to control for confounding factors. RESULTS: We identified 970 AMI cases and 2974 controls. Among cases, 11 (1.1%) and 185 (19.1%) were exposed to selective COX-2 inhibitors and conventional NSAIDs, respectively. Compared to non-use, none of these drug classes were associated with an increased risk of AMI (adjusted OR 1.07, 95% CI: 0.52-2.18 and 0.93, 95% CI: 0.77-1.12, respectively). Additional adjustment for potential confounders from patient's reports did not change the risk estimates (adjusted OR 1.08, 95% CI: 0.53-2.22 and 0.89, 95% CI: 0.73-1.09, respectively). WHAT IS NEW AND CONCLUSION: Additional confounding control for variables from self-reported data or considering self-reported OTC NSAID use did not change the risk estimates for the association between NSAIDs and AMI.

Cyclo-oxygenase selectivity and chemical groups of nonsteroidal anti-inflammatory drugs and the frequency of reporting hypersensitivity reactions: a case/noncase study in VigiBase.

To date, no reports of hypersensitivity reactions (HSRs) among nonsteroidal anti-inflammatory drugs (NSAIDs) according to cyclo-oxygenase (COX) selectivity and chemical groups have been published in a single study. The present study assessed the reporting frequency of HSRs for NSAIDs based on their relative inhibitory potency toward COX enzymes and chemical groups, including the presence/absence of a functional sulfonamide group, in strata observed 5 years after market authorization. A case/noncase study was performed among individual case safety reports (ICSRs) with NSAIDs as suspected drugs in VigiBase, the WHO spontaneous reporting database. Cases were ICSRs mentioning angioedema and anaphylactic/anaphylactoid shock conditions, while noncases were ICSRs without HSRs. NSAIDs were categorized into (i) NSAIDs with high COX-2 selectivity (coxibs), (ii) noncoxib NSAIDs with COX-2 preference, (iii) NSAIDs with poor selectivity, or (iv) NSAIDs with unknown selectivity. Chemical groups were defined based on the Anatomical Therapeutic Chemical classification system and the presence/absence of a functional sulfonamide group. Reporting odds ratios (RORs) and 95% confidence intervals (95% CIs) were calculated using logistic regression analysis. We identified 13 229 cases and 106 444 noncases. In the first 5 years after marketing, poor-selectivity NSAIDs and acetic acid derivatives were associated with the highest ROR of HSRs (age- and sex-adjusted ROR 2.12, 95% CI 1.98-2.28; and ROR 2.21, 95% CI 1.83-2.66, respectively) compared with coxibs, and sulfonamide NSAIDs were associated with the highest ROR of HSRs compared with nonsulfonamide NSAIDs (age- and sex-adjusted ROR 1.38, 95% CI 1.29-1.47). After the first 5 years of marketing, most of the RORs returned to approximately 1.

Non-steroidal anti-inflammatory drugs and the risk of out-of-hospital cardiac arrest: a case-control study.

AIMS: Non-steroidal anti-inflammatory drugs (NSAIDs), particularly selective COX-2 inhibitors, are associated with an increased risk of cardiovascular adverse events. However, the association between these drugs and out-of-hospital cardiac arrest with electrocardiogram-documented ventricular tachycardia/ventricular fibrillation (VT/VF-OHCA) has not been studied yet. This study was aimed to evaluate the association between the use of selective COX-2 inhibitors or conventional NSAIDs and VT/VF-OHCA compared with non-use. METHODS AND RESULTS: A case-control study was conducted among 2483 cases with VT/VF-OHCA from the AmsteRdam REsuscitation STudies (ARREST) registry, an ongoing Dutch registry of OHCA, and 10 441 non-VT/VF-OHCA-controls from the Dutch PHARMO Database Network, containing drug dispensing records of community pharmacies, over the period July 2005-December 2011. Up to five controls were matched for age and sex to one case at the date of VT/VF-OHCA (index date). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by conditional logistic regression analysis. Of the cases, 0.5% was currently exposed at the index date to selective COX-2 inhibitors and 2.5% to conventional NSAIDs. Neither current use of selective COX-2 inhibitors nor conventional NSAIDs were associated with an increased risk of VT/VF-OHCA (adjusted OR 1.11, 95% CI: 0.79-1.56 and adjusted OR 0.97, 95% CI: 0.86-1.10, respectively) compared with non-use. Stratification for VT/VF-OHCA with presence/absence of acute myocardial infarction did not change these results. CONCLUSION: Exposure to selective COX-2 inhibitors or conventional NSAIDs was not associated with an increased risk of VT/VF-OHCA compared with non-use.

Gastrointestinal toxicity among patients taking selective COX-2 inhibitors or conventional NSAIDs, alone or combined with proton pump inhibitors: a case-control study.

PURPOSE: To assess the risk of gastrointestinal perforation, ulcers, or bleeding (PUB) associated with the use of conventional nonsteroidal anti-inflammatory drugs (NSAIDs) with proton pump inhibitors (PPIs) and selective COX-2 inhibitors, with or without PPIs compared with conventional NSAIDs. METHODS: A case-control study was performed within conventional NSAIDs and/or selective COX-2 inhibitors users identified from the Dutch PHARMO Record Linkage System in the period 1998-2012. Cases were patients aged ≥18 years with a first hospital admission for PUB. For each case, up to four controls were matched for age and sex at the date a case was hospitalized (index date). Logistic regression analysis was used to calculate odds ratios (ORs). RESULTS: At the index date, 2634 cases and 5074 controls were current users of conventional NSAIDs or selective COX-2 inhibitors. Compared with conventional NSAIDs, selective COX-2 inhibitors with PPIs had the lowest risk of PUB (adjusted OR 0.51, 95% confidence interval [CI]: 0.35-0.73) followed by selective COX-2 inhibitors (adjusted OR 0.66, 95%CI: 0.48-0.89) and conventional NSAIDs with PPIs (adjusted OR 0.79, 95%CI: 0.68-0.92). Compared with conventional NSAIDs, the risk of PUB was lower for those aged ≥75 years taking conventional NSAIDs with PPIs compared with younger patients (adjusted interaction OR 0.79, 95%CI: 0.64-0.99). However, those aged ≥75 years taking selective COX-2 inhibitors, the risk was higher compared with younger patients (adjusted interaction OR 1.22, 95%CI: 1.01-1.47). CONCLUSIONS: Selective COX-2 inhibitors with PPIs, selective COX-2 inhibitors, and conventional NSAIDs with PPIs were associated with lower risks of PUB compared with conventional NSAIDs. These effects were modified by age. © 2017 The Authors. Pharmacoepidemiology & Drug Safety Published by John Wiley & Sons Ltd.