PMID- 16387565
OWN - NLM
STAT- MEDLINE
DCOM- 20060306
LR  - 20151119
IS  - 0002-9149 (Print)
IS  - 0002-9149 (Linking)
VI  - 96
IP  - 12B
DP  - 2005 Dec 26
TI  - Cardiac safety in clinical trials of phosphodiesterase 5 inhibitors.
PG  - 37M-41M
AB  - Phosphodiesterase type 5 (PDE5) inhibitors have revolutionized the treatment of 
      erectile dysfunction (ED). Those safe and effective agents were originally 
      developed for their cardiovascular effects and were incidentally found to enhance 
      erections. Since the introduction of the first PDE5 inhibitor, sildenafil, in 
      1998, there has been concern about the effects of these agents on the heart and 
      their safety in patients with cardiovascular disease. The concerns focused on the 
      effects on blood pressure and heart rate, cardiac electrophysiology, and 
      cardiovascular adverse events in clinical trials. Since there are currently three 
      PDE5 inhibitors, attention has been given to class effects as well as unique 
      individual safety and adverse events. Since these drugs are mild vasodilators, 
      all three have blood pressure-lowering effects. These effects are usually mild 
      and produce few symptoms. When combined with the nitric oxide donor 
      nitroglycerine, however, blood pressure drops may be profound and life 
      threatening. All three agents are contraindicated with nitrates. Cardiac 
      electrophysiology effects, especially as manifested by changes in the QT 
      interval, have been studied. None of the three agents are dangerously associated 
      with QTc prolongation, although vardenafil has a warning for patients at risk for 
      QTc prolongation. In evaluating cardiovascular adverse events in clinical trials, 
      no signal to danger can be convincingly cited. Indeed, with the vasodilator 
      effects of these drugs, many studies point to the improved exercise tolerance and 
      coronary dilation in patients taking PDE5 inhibitors. PDE5 inhibitors are 
      effective in treating ED, and their safety profile is excellent. There do not 
      appear to be significant cardiovascular safety issues in the man with 
      satisfactory cardiac and performance status.
FAU - Carson, Culley C 3rd
AU  - Carson CC 3rd
AD  - University of North Carolina School of Medicine at Chapel Hill, North Carolina 
      27599-7235, USA. carson@med.unc.edu
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20051205
PL  - United States
TA  - Am J Cardiol
JT  - The American journal of cardiology
JID - 0207277
RN  - 0 (Carbolines)
RN  - 0 (Imidazoles)
RN  - 0 (Phosphodiesterase Inhibitors)
RN  - 0 (Piperazines)
RN  - 0 (Purines)
RN  - 0 (Sulfones)
RN  - 0 (Triazines)
RN  - 5O8R96XMH7 (Vardenafil Dihydrochloride)
RN  - 742SXX0ICT (Tadalafil)
RN  - BW9B0ZE037 (Sildenafil Citrate)
RN  - EC 3.1.4.- (Phosphoric Diester Hydrolases)
RN  - EC 3.1.4.35 (3',5'-Cyclic-GMP Phosphodiesterases)
RN  - EC 3.1.4.35 (Cyclic Nucleotide Phosphodiesterases, Type 5)
RN  - EC 3.1.4.35 (PDE5A protein, human)
SB  - IM
MH  - 3',5'-Cyclic-GMP Phosphodiesterases
MH  - Blood Pressure/drug effects
MH  - Carbolines/adverse effects
MH  - Clinical Trials as Topic
MH  - Coronary Artery Disease/*physiopathology
MH  - Cyclic Nucleotide Phosphodiesterases, Type 5
MH  - Electrophysiology
MH  - Erectile Dysfunction/*drug therapy/physiopathology
MH  - Heart Rate/drug effects
MH  - Humans
MH  - Imidazoles/adverse effects
MH  - Male
MH  - Phosphodiesterase Inhibitors/administration & dosage/*adverse effects
MH  - Phosphoric Diester Hydrolases/*drug effects
MH  - Piperazines/adverse effects
MH  - Purines
MH  - Sildenafil Citrate
MH  - Sulfones/adverse effects
MH  - Tadalafil
MH  - Triazines/adverse effects
MH  - Vardenafil Dihydrochloride
RF  - 25
EDAT- 2006/01/03 09:00
MHDA- 2006/03/07 09:00
CRDT- 2006/01/03 09:00
PHST- 2006/01/03 09:00 [pubmed]
PHST- 2006/03/07 09:00 [medline]
PHST- 2006/01/03 09:00 [entrez]
AID - S0002-9149(05)01125-2 [pii]
AID - 10.1016/j.amjcard.2005.07.010 [doi]
PST - ppublish
SO  - Am J Cardiol. 2005 Dec 26;96(12B):37M-41M. doi: 10.1016/j.amjcard.2005.07.010. 
      Epub 2005 Dec 5.