Phosphodiesterase type 5 inhibition is a novel therapeutic option in Raynaud disease.
BACKGROUND
Raynaud disease (RD) is a common disorder affecting 3% to 5% of the healthy population, and occurs in more than 90% of patients with connective tissue diseases. The therapeutic options remain limited, particularly in patients with secondary RD due to connective tissue disease. Theoretical considerations lead to the expectation that phosphodiesterase type 5 inhibitors may improve clinical symptoms and digital blood flow in patients with RD.


METHODS
We conducted an open-label pilot study in 40 patients with RD, 33 (82%) of whom had secondary and 7 (18%) of whom had primary RD. Digital blood flow was measured by laser-Doppler flowmetry at room temperature and during the cold-exposure test before medical treatment, 1 hour after the initial intake, and after 2 weeks of continuous treatment (10 mg twice a day) with the novel phosphodiesterase type 5 inhibitor vardenafil. Clinical symptoms were recorded by a patient questionnaire and summarized as the Raynaud condition score.


RESULTS
Laser-Doppler flowmetry revealed that vardenafil improved digital blood flow in 28 (70%) patients, whereas 12 (30%) did not respond. In individuals responding, digital blood flow significantly increased by a mean +/- SEM of 21.0% +/- 4.9% and 30.0% +/- 5.7% at 1 hour and 2 weeks of treatment at room temperature, respectively, and by 18.8% +/- 4.4% and 35.1% +/- 7.5% at 1 hour and 2 weeks during the cold-exposure test, respectively (P < .01 for all). Consistently, clinical symptoms improved in 27 (68%) of the 40 patients, and the Raynaud condition score declined from a mean +/- SEM of 5.05 +/- 0.38 to 3.54 +/- 0.31 (P < .001).


CONCLUSIONS
Our data indicate that phosphodiesterase type 5 inhibition significantly improves peripheral blood flow and clinical symptoms in a large subset of patients with RD and, thus, may provide a novel therapeutic approach in such individuals.
Caglayan
Evren
E
Klinik III für Innere Medizin, Universität zu Köln, Köln, Germany.
Huntgeburth
Michael
M
Karasch
Thomas
T
Weihrauch
Julia
J
Hunzelmann
Nicolas
N
Krieg
Thomas
T
Erdmann
Erland
E
Rosenkranz
Stephan
S
D015106:3',5'-Cyclic-GMP Phosphodiesterases; D000328:Adult; D001783:Blood Flow Velocity; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D017078:Laser-Doppler Flowmetry; D008297:Male; D008875:Middle Aged; D017060:Patient Satisfaction; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D010727:Phosphoric Diester Hydrolases; D010865:Pilot Projects; D011336:Probability; D011928:Raynaud Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology*; D018570:Risk Assessment; D012720:Severity of Illness Index; D016896:Treatment Outcome
D010726:Phosphodiesterase Inhibitors; D010727:Phosphoric Diester Hydrolases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517381:PDE5A protein, human