Incident Neutropenia in New Users of Different Non-opioid Analgesics: An Observational Propensity Score-Controlled Cohort Study.

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 agranulocytosis (HR between 0.19 and 0.51).

CONCLUSION

Our results indicate no risk of neutropenia for NSAIDs when compared to paracetamol. An increased risk of agranulocytosis in association with paracetamol is possible, but residual confounding by frailty may at least partially explain this association.