Cardiovascular risk with cyclooxygenase inhibitors: general problem with substance specific differences?
Randomised clinical trials and observational studies have shown an increased risk of myocardial infarction, stroke, hypertension and heart failure during treatment with cyclooxygenase inhibitors. Adverse cardiovascular effects occurred mainly, but not exclusively, in patients with concomitant risk factors. Cyclooxygenase inhibitors cause complex changes in renal, vascular and cardiac prostanoid profiles thereby increasing vascular resistance and fluid retention. The incidence of cardiovascular adverse events tends to increase with the daily dose and total exposure time. A comparison of individual selective and unselective cyclooxygenase inhibitors suggests substance-specific differences, which may depend on differences in pharmacokinetic parameters or inhibitory potency and may be contributed by prostaglandin-independent effects. Diagnostic markers such as N-terminal pro brain natriuretic peptide (NT-proBNP) or high-sensitive C-reactive protein might help in the early identification of patients at risk, thus avoiding the occurrence of serious cardiovascular toxicity.
Pharmazentrum Frankfurt/ZAFES, Institut für Klinische Pharmakologie, Klinikum der Johann Wolfgang Goethe-Universität Frankfurt, Theodor Stern Kai 7, 60590, Frankfurt am Main, Germany. tegeder@em.uni-frankfurt.de
Irmgard
I
Tegeder
Gerd
G
Geisslinger
D002318:Cardiovascular Diseases / Q000139:chemically induced*; D000068579:Celecoxib; D049109:Cell Proliferation / Q000187:drug effects; D002986:Clinical Trials as Topic; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects*; D006333:Heart Failure / Q000139:chemically induced; D006487:Hemostasis / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D007783:Lactones / Q000009:adverse effects; D009288:Naproxen / Q000009:adverse effects; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D011720:Pyrazoles / Q000009:adverse effects; D013449:Sulfonamides / Q000009:adverse effects; D013450:Sulfones / Q000009:adverse effects
D016861:Cyclooxygenase Inhibitors; D007783:Lactones; D010446:Peptide Fragments; D011720:Pyrazoles; D013449:Sulfonamides; D013450:Sulfones; C109794:pro-brain natriuretic peptide (1-76); C116926:rofecoxib; D020097:Natriuretic Peptide, Brain; D009288:Naproxen; D000068579:Celecoxib