Ibuprofen or Tylenol for Fever - Surprise

Sorry for the long delay in writing a blog post.  From now on, expect a weekly edition of Siriasis .

Motivation: On the inpatient service, when someone has fever, the first line of symptomatic treatment is administration of acetaminophen.  This summer, however, when I was febrile for a few days with a viral illness, I found that I had better control of fever with ibuprofen than with acetaminophen.  I wondered is acetaminophen really better than ibuprofen?  What are the data?

Paper: Efficacy and Safety of Ibuprofen and Acetaminophen in Children and Adults: A Meta-Analysis and Qualitative Review.  Pierce, C.A., The Annals of Pharmacotherapy (2010) Vol. 44: 489-506. 

Type of Study: A meta-analysis containing randomized controlled trials studies that directly compared ibuprofen to acetaminophen and provided comparative safety data.  The authors analyzed pediatric and adult populations separately.  While analyzing adverse events, the authors excluded expected side-effects such as GI disturbance for ibuprofen and mild liver enzyme abnormalities for tylenol from "serious" side effects.

Results:
Analgesic efficacy in adults: Out of 36 studies included, 26 concluded that ibuprofen was superior to acetaminophen.  No study showed acetaminophen superiority.  The overall effect size was medium (standardized mean difference of 0.69(CI: 0.57 to 0.81)). 

Antipyretic efficacy in adults:  Of the five studies, three concluded that ibuprofen was superior while two found no difference.  Of note, not all of these studied infectious fevers - some studied fever caused by iatrogenic sources like interferon injections.

Antipyretic efficacy in children: Meta-analysis of seven trials concluded that fever control at four hours is significantly better with ibuprofen compared to acetaminophen - the effect size is relatively small (standardized mean difference of 0.26 (0.10 to 0.41)).

Adverse events: When taken as directed in adults and children, the odds of suffering at least one adverse event is not significantly different between ibuprofen to acetaminophen.  When taken as directed, very few serious adverse events occur in either arm.

Limitations of Data: There are a number of limitations in the meta-analysis.  To me, the chief one is that no single model of fever is considered.  Rather, the efficacy of treating fever caused by diverse causes is lumped together.  While potentially powerful in one sense since you can apply the data to fever from any source, we don't know if subgroups benefit differently.  Also, for adverse events, excluding GI side-effects from ibuprofen group may have changed the results.

Conclusion: For fever, good data do not exist for adults, but in the pediatric population and extrapolating from this population, ibuprofen is likely a better anti-pyretic compared to acetaminophen.  As an analgesic, ibuprofen is better for adults.  Also, excluding expected side effects for the drugs, acetaminophen and ibuprofen do not carry additional toxicity.  My conclusion is that in the outpatient setting if patient does not have history of serious risk factors for GI bleeding, better fever control and analgesia are likely achieved by prescribing time limited doses of ibuprofen.

Link to paper: http://www.theannals.com/cgi/content/full/44/3/489