Incident Neutropenia in New Users of Different Non-opioid Analgesics: An Observational Propensity Score-Controlled Cohort Study
Abstract
Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) and paracetamol have been associated with neutropenia and agranulocytosis with inconsistent results.
Objective: To investigate the risk of neutropenia in association with frequently used NSAIDs compared to paracetamol.
Methods: We conducted a cohort study using the UK-based Clinical Practice Research Datalink (CPRD) GOLD. In three pairwise comparisons, we compared the risk of neutropenia including agranulocytosis (defined by Read codes) between new NSAID users (diclofenac, ibuprofen, and naproxen) and new paracetamol users (active comparator) during a maximum follow up of 60 days. Secondary and tertiary outcomes additionally included (1) in-patient diagnosed agranulocytosis and (2) laboratory values indicating neutropenia. Both were additionally restricted to only agranulocytosis. We applied propensity score-fine stratification to control for measured confounding and quantified incidence rates (IRs) as well as hazard ratios (HRs) with 95% confidence intervals (CIs).
Results: Our weighted cohorts included 1,003,314 (paracetamol) to 2,207,612 (diclofenac) patients. Weighted IRs of neutropenia (primary outcome) were between 2.1/10,000 person years (PYs) and 2.3/10,000 PYs. HRs for the primary outcome ranged between 1.00 (95% CI 0.51-1.94) and 1.12 (95% CI 0.57-2.23) for NSAIDs versus paracetamol. The secondary and tertiary outcome yielded reduced HRs between 0.53 and 1.03, and even lower HRs when restricted to…
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Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence.
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