Safety of intravenous nitroglycerin after administration of sildenafil citrate to men with coronary artery disease: a double-blind, placebo-controlled, randomized, crossover trial.
OBJECTIVE
Although contraindicated, there are situations when a patient who has recently taken a phosphodiesterase 5 inhibitor (e.g., sildenafil) might need intravenous nitroglycerin (NTG) treatment. This study determined if, and at what dose, intravenous NTG could be administered safely to men with coronary artery disease who had recently ingested sildenafil.


METHODS
Double-blind, placebo-controlled, randomized, crossover trial.


METHODS
Four clinical practice sites in Canada, Scotland, and the United States.


METHODS
A total of 34 men (>or=35 yrs) with a history of angina pectoris and coronary artery disease (>50% stenosis of at least one coronary artery), most of whom were taking antihypertensives.


METHODS
Sildenafil (100 mg) or placebo (single dose; crossover after 3-7 days) followed 45 mins later by escalating doses of intravenous NTG (160 microg/min maximum).


RESULTS
After sildenafil, there were slightly greater maximum (supine) blood pressure decreases and heart rate increases (e.g., 4 to 6 mm Hg [systolic] and <or=1 beat/min, at NTG doses of <or=80 microg/min) than after placebo. The median maximum tolerated NTG dose (range) was 80 (0-160) microg/min for sildenafil vs. 160 (20-160) microg/min for placebo (adjusted mean +/- se, 77 +/- 7 vs. 127 +/- 7; p < .0001; analysis of variance), and NTG 160 microg/min was tolerated by eight (25%) and 19 (59%) men, respectively (p = .0008). Treatment-related adverse events were mostly mild/moderate hypotension, headache, and dizziness, which are often associated with NTG alone. Sildenafil and metabolite plasma concentrations were lower than previously reported in healthy men.


CONCLUSIONS
With close monitoring of blood pressure and heart rate, men with stable coronary artery disease who have taken sildenafil may tolerate intravenous NTG (<or=160 microg/min) with low starting dosage and gradual upward titration. The hemodynamic response might be different in subgroups not specifically examined in the study (e.g., men presenting with acute coronary symptoms). The explanation for the lower than expected plasma concentrations remains uncertain.
Parker
John D
JD
Department of Medicine, University Health Network and Mount Sinai Hospitals, University of Toronto, Ontario, Canada. John.Parker@uhn.on.ca
Bart
Bradley A
BA
Webb
David J
DJ
Koren
Michael J
MJ
Siegel
Richard L
RL
Wang
Hao
H
Malhotra
Bimal
B
Jen
Frank
F
Glue
Paul
P
D000368:Aged; D000369:Aged, 80 and over; D001775:Blood Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000188:drug therapy*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004347:Drug Interactions; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D010879:Piperazines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D011687:Purines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*
D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate; D005996:Nitroglycerin