Aspirin inhibits the acute venodilator response to furosemide in patients with chronic heart failure.
OBJECTIVE
We sought to determine the effect of aspirin on the venodilator effect of furosemide in patients with chronic heart failure (CHF) BACKGROUND: Furosemide has an acute venodilator effect preceding its diuretic action, which is blocked by nonsteroidal anti-inflammatory, drugs. The ability of therapeutic doses of aspirin to block this effect of furosemide in patients with CHF has not been studied. For comparison, the venodilator response to nitroglycerin (NTG) was also studied.


METHODS
Eleven patients with CHF were randomized to receive placebo, aspirin at 75 mg/day or aspirin at 300 mg/day for 14 days in a double-blind, crossover study. The effect of these pretreatments on the change in forearm venous capacitance (FVC) after 20 mg of intravenous furosemide was measured over 20 min by using venous occlusion plethysmography. In a second study, the effect of 400 microg of sublingual NTG on FVC was documented in 11 similar patients (nine participated in the first study).


RESULTS
Mean arterial pressure, heart rate and forearm blood flow did not change in response to furosemide. After placebo pretreatment, furosemide caused an increase in FVC of 2.2% (95% confidence interval [CI] -0.9% to 5.2%; mean response over 20 min). By comparison, FVC fell by -1.1% (95% CI -4.2% to 1.9%) after pretreatment with aspirin at 75 mg/day, and by -3.7% (95% CI -6.8% to -0.7%) after aspirin at 300 mg/day (p = 0.020). In the second study, NTG increased FVC by 2.1% (95% CI -1.6% to 5.8%) (p = 0.95 vs. furosemide).


CONCLUSIONS
In patients with CHF, venodilation occurs within minutes of the administration of intravenous dose of furosemide. Our observation that aspirin inhibits this effect further questions the use of aspirin in patients with CHF.
Jhund
P S
PS
Clinical Research Initiative in Heart Failure, University of Glasgow, United Kingdom.
Davie
A P
AP
McMurray
J J
JJ
D000368:Aged; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects*; D002908:Chronic Disease; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005542:Forearm / Q000098:blood supply; D005665:Furosemide / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D005996:Nitroglycerin / Q000008:administration & dosage; D010991:Plethysmography; D014664:Vasodilation / Q000187:drug effects*; D014680:Veins / Q000187:drug effects
D005665:Furosemide; D005996:Nitroglycerin; D001241:Aspirin