Acute administration of diclofenac, but possibly not long term low dose aspirin, causes detrimental renal effects in heart failure patients treated with ACE-inhibitors.
BACKGROUND
Non-steroidal anti-inflammatory drugs (NSAID) or high doses of aspirin (acetylsalicylic acid) can exert detrimental effects on renal function and counteract the beneficial effects of angiotensin-converting enzyme (ACE) inhibitors in patients with congestive heart failure.


OBJECTIVE
The objective of our study was to evaluate the renal effects of low dose aspirin and the NSAID diclofenac in patients with congestive heart failure treated with ACE-inhibitors.


METHODS
Ten patients on their individually titrated dose of ACE-inhibitors and low dose aspirin (< or =125 mg daily) with stable congestive heart failure from coronary artery disease, entered an open investigation while on low dose aspirin, which was then discontinued. After one week wash-out they received an oral dose of 50 mg diclofenac potassium or placebo in a double-blind cross-over fashion with a one week wash-out period between treatments.


RESULTS
Diclofenac caused significant (P<0.05) decreases in GFR, urine flow, osmolality clearance, and excretion rates of sodium and potassium compared to placebo and aspirin. At t(max) for diclofenac or corresponding time for placebo diclofenac caused 40 (11-59)% (geometric mean and 95% confidence limits) reduction in GFR compared to placebo and 36 (5.4-56)% reduction to low-dose aspirin. No significant changes between low dose aspirin and placebo were found.


CONCLUSIONS
Acute administration of diclofenac, but not long term low dose aspirin, has profound impact on renal function in patients with heart failure treated with ACE-inhibitors and may cause worsened heart failure.
Juhlin
Tord
T
Department of Cardiology, Malmö University Hospital, Malmö, Sweden.
Björkman
Sven
S
Gunnarsson
Bodil
B
Fyge
Asa
A
Roth
Bodil
B
Höglund
Peter
P
D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects*; D001241:Aspirin / Q000008:administration & dosage*; D003404:Creatinine / Q000097:blood; D018592:Cross-Over Studies; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage*; D004008:Diclofenac / Q000008:administration & dosage* / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009318:Natriuresis / Q000187:drug effects; D009994:Osmolar Concentration; D011188:Potassium / Q000378:metabolism; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D004008:Diclofenac; D003404:Creatinine; D001241:Aspirin; D011188:Potassium