Cardiovascular risks associated with use of non-steroidal anti-inflammatory drugs in patients with non-obstructive coronary artery disease.

AIMS: To examine whether non-aspirin non-steroidal anti-inflammatory drug (NSAID) use is associated with increased cardiovascular risks in patients with non-obstructive coronary artery disease (CAD). METHODS AND RESULTS: Using Danish medical registries, we conducted a population-based cohort study in Western Denmark during 2008-17. We identified all patients undergoing first-time coronary computed tomography angiography (CCTA) due to suspected CAD (n = 35 399), with results showing no (n = 28 581) or non-obstructive CAD (n = 6818). Multivariate Cox regression was used to compute hazard ratios of major adverse cardiac events (MACEs), including incident myocardial infarction, coronary intervention, and death. The rate of MACE increased by 33% for any NSAID use compared with non-use [hazard ratio 1.33, 95% confidence interval (CI) 1.06-1.68] in patients with no CAD and by 48% (1.48, 95% CI 1.06-2.07) in patients with non-obstructive CAD. Rate difference of MACE, per 100 person-years, was 0.38 (95% CI 0.08-0.67) in patients with no CAD (number needed to harm: 267) and 1.08 (95% CI 0.06-2.11) in patients with non-obstructive CAD (number needed to harm: 92). Current use of older cyclooxygenase-2 inhibitors was associated with the highest hazard ratio in patients with non-obstructive CAD, both when ascertained as pre-CCTA use (2.9-fold increase) and when ascertained from time-varying use (1.8-fold increase). CONCLUSION: NSAID use in patients with CCTA-confirmed no and non-obstructive CAD was associated with an increased cardiovascular risk compared with non-use. The absolute risk differences and numbers needed to harm were considered clinically relevant, particularly in patients with non-obstructive CAD.

The Validity of Danish Prescription Data to Measure Use of Aspirin and Other Non-Steroidal Anti-Inflammatory Drugs and Quantification of Bias Due to Non-Prescription Drug Use.

PURPOSE: To evaluate the potential of Danish prescription registries to capture aspirin and non-aspirin non-steroidal anti-inflammatory drug (NSAID) use and to quantitatively evaluate the magnitude of bias from misclassification of true NSAID and aspirin use as apparent non-use in drug outcome studies. PATIENTS AND METHODS: In a population-based cohort study, we retrieved sales statistics for NSAIDs and aspirins based on nationwide data from the Danish Health Data Authority and the Danish National Prescription Registry. We estimated prevalence of recorded and non-recorded NSAID use in the prescription registry and resulting proportions of true NSAID and aspirin use misclassified as apparent non-use from 1999 to 2019 at population and patient levels. RESULTS: The prevalence of true use misclassified as non-use (mainly due to over-the-counter use) peaked at 4.7% in 2012 for NSAIDs overall, 5.5% in 2012 for ibuprofen, and at 5.9% in 2002 for high-dose aspirin. Misclassification of other individual NSAIDs was near null. Misclassification of true low-dose aspirin use as non-use declined during the study period but remained around 1% since 2005. In subgroups of cardiac patients, the highest prevalence of true NSAID use misclassified as non-use was 5.0% in 2002 and 4.3% in 2017. Quantitative bias analyses showed how such misclassification of true NSAID and aspirin use as non-use remained minimal both at population and patient levels. In hypothetical examples simulating real study populations with differing exposure prevalence and prevalence of true NSAID and aspirin use misclassified as apparent non-use, the approximate percentage change due to misclassification of use as non-use did not exceed 5% and in most scenarios stayed around 1%. CONCLUSION: The Danish prescription registries are valid data sources for assessing the effects of aspirin and NSAID use. The influence of non-recorded NSAID and aspirin use on estimates of association is virtually negligible.