Non-steroidal Anti-inflammatory Drugs may Worsen the Course of Community-Acquired Pneumonia: A Cohort Study

Basille, Damien; Plouvier, Nathalie; Trouve, Charlotte; Duhaut, P.; Andréjak, Claire; Jounieaux, Vincent

doi:10.1007/s00408-016-9973-1

Cited by 45 publications

(48 citation statements)

References 30 publications

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“…that NSAIDs were used to treat the earliest manifestations of a yet undiagnosed pneumonia) or detection bias suggested in previous studies. 10,11 In both analyses, follow-up continued until the earliest of outcome occurrence, end of study period (Sept 30 2015), crossover of exposure group or addition of comparator drug, medical or pharmacy disenrollment, death or 365 days post index date.…”

Section: Discussionmentioning

confidence: 99%

“…The risk of pneumonia was strongest in the 5 days after exposure to oral NSAIDs, but weakened when these 5 days of follow up were removed from the analysis (main analysis)suggesting protopathic bias. [10][11][12] Prior research has found that individuals treated with NSAIDs in the days preceding admission to hospital for pneumonia had more severe presentations, possibly due to altered immune responses and longer times to antibiotic treatment. 11,12 Severe presentations increase the likelihood of pneumonia being diagnosed or detected.…”

Section: Discussionmentioning

confidence: 99%

“…In the days following NSAID exposure, and after respiratory symptoms worsen, the patient is correctly diagnosed as having pneumonia. [10][11][12] In a second subgroup analysis we excluded patients with a history of cancer, cirrhosis, COPD, cystic fibrosis, HIV positive status or tracheostomy in the year prior to cohort entry given their increased risk of pneumonia and to help mimic cohorts in prior studies. 10,11…”

Section: Nsaids and Pneumonia Substudymentioning

confidence: 99%

“…In contrast, prior literature examining the relationship between NSAIDs and pulmonary complications in pneumonia has suggested protopathic bias as a possible explanation for the association. [10][11][12] Further impetus for focusing on these signals stemmed from macrolide antibiotics and NSAIDs being frequently used drugs across the entire population, thus even a small increase in the risk of heart failure or pneumonia could pose an important public health burden.…”

Section: Introductionmentioning

confidence: 99%

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Evaluating signals generated in a large-scale sequence symmetry analyses: macrolides and heart failure; and NSAIDs and pneumonia

Sinnott

Lin

Wang

et al. 2020

Preprint

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Objective Using US claims data and the most up-to-date pharmacoepidemiological study design tools we aimed to investigate two safety signals for (1) macrolides and heart failure; and (2) non-steroidal anti-inflammatory drugs (NSAIDs) and pneumonia generated from a large-scale screening analysis using a self-controlled sequence symmetry design in Danish data. Methods We used IBM Marketscan data to conduct two new-user, active-comparator cohort studies. In the macrolides example, the exposure was clarithromycin or azithromycin and the comparator was amoxicillin/clavulanate, in patients with sinusitis. In the NSAIDs example, the exposure was oral NSAIDs and the comparator was topical diclofenac, in patients with osteoarthritis. We used Cox proportional hazards regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) to adjust for approximately 50 investigator-specified confounders in a propensity score (PS) matched analysis. In a secondary analysis, we used high-dimensional PS (hd-PS) to adjust for 200 additional proxy confounders. Results We had 1,012,364 propensity score matched patients exposed to clarithromycin or azithromycin versus amoxicillin/clavulanate. With 162 outcomes among clarithromycin or azithromycin exposed patients and 134 among amoxicillin/clavulanate, the HR for overall heart failure was 1.14 (95% CI 0.90-1.43). In the NSAIDs example, we included 94,490 patients after propensity score matching. With 794 pneumonia outcomes among oral NSAID patients and 700 among topical diclofenac, we found HR 0.98 (95% CI 0.89-1.09). Some upward bias was suspected as larger HRs were observed in the days immediately following exposure for both the macrolides and NSAIDs examples. We found similar results in the hd-PS matched analyses for both examples. Conclusion Our findings for NSAIDs and pneumonia suggest the original signal may have been due to protopathic or detection bias. Our analyses for macrolides and heart failure with short-term follow-up also suggest bias, although we encourage further research.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Nsaids and Pneumonia Substudymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Evaluating signals generated in a large-scale sequence symmetry analyses: macrolides and heart failure; and NSAIDs and pneumonia

Sinnott

Lin

Wang

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…NSAIDs intake was independently associated with the development of pleuroparenchymal complications (odds ratio = 2.57 [1.02-6.64], p = 0.049). Nevertheless, given the lack of consistent results about the direct effect of NSAIDs on the immunological response and the lack of controlled randomized studies in human, the authors could not conclude a direct effect of NSAIDs in the development of the complications of CAP [5]. Surely, in addition to the supposed interfering effect of NSAIDs with responses mediated by the prostaglandin and leukotriene pathways, NSAIDs, together with other antipyretic and analgesic medications, can be responsible for later presentation of symptoms or underestimation of the severity of the disease, both leading to a delayed diagnosis and possible worse prognosis.…”

mentioning

confidence: 99%