Risk of stroke associated with nonsteroidal anti-inflammatory drugs

Figures & data

Figure 1 Effects of COX inhibition on vasculature.

Abbreviation: COX, cyclooxygenase.

Figure 2 Relative COX-1/COX-2 selectivity of various nonselective NSAIDs.

Note: This chart represents the log (IC₅₀ of COX-1 relative to the IC₅₀ of COX-2) for various nonselective NSAIDs. Adapted with permission Cryer B, Feldman M. Cyclooxygenase-1 and cyclooxygenase-2 selectivity of widely used nonsteroidal anti-inflammatory drugs. Am J Med. 1998;104(5):413–421.¹⁰ © Copyright 1998, with permission Elsevier.
Abbreviations: COX, cyclooxygenase; IC₅₀, half maximal inhibitory concentration; NSAID, nonsteroidal anti-inflammatory drug.

Table 1 Potential mechanisms for NSAID-associated increase in stroke risk

Vasoconstriction secondary to inhibition of prostacyclin-induced vasodilation

Hypertension induced by direct renal effects on sodium excretion leading to volume expansion

Thrombosis due to prostaglandin-mediated platelet aggregation

Abbreviation: NSAID, nonsteroidal anti-inflammatory drug.

Table 2 Hazard ratios of various NSAIDs from observational studies

	Type of stroke	NSAID type	RR or OR (CI)
Bak et al^Citation30	Ischemic	Any	1.2 (1.0–1.4)
Abraham et al^Citation31	Ischemic or hemorrhagic	*Highly selective	1.6 (1.2–2.2)
Andersohn et al^Citation32	Ischemic	Rofecoxib	1.71 (1.33–2.18)
		Etoricoxib	2.38 (1.10–1.53)
		Celecoxib	1.07 (0.79–1.44)
Solomon et al^Citation33	Ischemic	Rofecoxib	1.15 (1.04–1.26)
		Celecoxib	1.00 (0.92–0.09)
Roumie et al^Citation34	Ischemic or hemorrhagic	Rofecoxib	1.28 (1.06–1.53)
		Valdecoxib	1.41 (1.04–1.91)
		Celecoxib	1.04 (0.87–1.23)
Haag et al^Citation35	Ischemic or hemorrhagic	Any	1.58 (1.19–2.08)

Note:

* Highly selective: rofecoxib, valdecoxib, parecoxib and lumiracoxib.

Abbreviations: CI, confidence interval; NSAID, nonsteroidal anti-inflammatory drug; OR, odds ratio; RR, relative risk.

CryerBFeldmanMCyclooxygenase-1 and cyclooxygenase-2 selectivity of widely used nonsteroidal anti-inflammatory drugsAm J Med199810454134219626023

 PubMed Web of Science ®Google Scholar

BakSAndersenMTsiropoulosIRisk of stroke associated with nonsteroidal anti-inflammatory drugs: a nested case-control studyStroke200334237938612574546

 PubMed Web of Science ®Google Scholar

AbrahamNSEl-SeragHBHartmanCRichardsonPDeswalACyclooxygenase-2 selectivity of non-steroidal anti-inflammatory drugs and the risk of myocardial infarction and cerebrovascular accidentAliment Pharmacol Ther200725891392417402995

 PubMed Web of Science ®Google Scholar

AndersohnFSchadeRSuissaSGarbeECyclooxygenase-2 selective nonsteroidal anti-inflammatory drugs and the risk of ischemic stroke: a nested case-control studyStroke20063771725173016728684

 PubMed Web of Science ®Google Scholar

SolomonDHAvornJStürmerTGlynnRJMogunHSchneeweissSCardiovascular outcomes in new users of coxibs and nonsteroidal antiinflammatory drugs: high-risk subgroups and time course of riskArthritis Rheum20065451378138916645966

 PubMed Web of Science ®Google Scholar

RoumieCLMitchelEFKaltenbachLArbogastPGGideonPGriffinMRNonaspirin NSAIDs, cyclooxygenase 2 inhibitors, and the risk for strokeStroke20083972037204518436878

 PubMed Web of Science ®Google Scholar

HaagMDBosMJHofmanAKoudstaalPJBretelerMMStrickerBHCyclooxygenase selectivity of nonsteroidal anti-inflammatory drugs and risk of strokeArch Intern Med2008168111219122418541831

 PubMed Web of Science ®Google Scholar