New research adds to evidence that because of their vasodilatory properties, phosphodiesterase type 5 (PDE5) inhibitors may be a useful therapeutic option for the treatment of Raynaud's disease (RD), according to a new study in the January 23, 2006, issue of the Archives of Internal Medicine.1

In the open-label pilot study, the 40 patients who received 10 mg twice a day of the PDE5 inhibitor vardenafil (Levitra®) for 2 weeks showed significant improvements in peripheral blood flow and clinical symptoms. Eighty-two percent of this cohort of patients had secondary RD, which frequently occurs with connective tissue diseases and is notoriously difficult to treat.

"Our findings indicate that PDE5 inhibitors like vardenafil significantly improve 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," conclude the researchers, led by Evren Caglayan, MD, of the Klinik III fur Innere Medizin at the Universität zu Köln in Köln, Germany. "Based on these findings, a placebo-controlled trial and a comparison and/or combination with established medications are highly warranted," they conclude.

The researchers suggest that PDE5 inhibition may improve RD by exerting both vasodilatory properties and antiproliferative effects, particularly in diseased tissue.

For the study, the investigators measured digital blood flow with laser-Doppler flowmetry at room temperature at baseline, 1 hour after the initial intake, and after 2 weeks of continuous treatment. Measurements were repeated during a cold-exposure test. Patients also filled out questionnaires to help researchers assess the frequency, total daily duration, and severity of RD-related attacks, as well as to rate the effect of the disease on their lives.

According to the findings, vardenafil improved digital blood flow in 70% of patients, whereas 30% did not respond. In individuals responding to the treatment, 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. Overall, clinical symptoms improved in 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), the new study showed.

Sildenafil also effective in RD treatment

Roland Fries, MD, associate professor of internal medicine at the University of Saarlandes in Homburg, Germany, and colleagues recently published a study showing that another PDE5 inhibitor, sildenafil (Viagra®), also relieved symptoms of RD.2

In this study of 16 patients with severe RD, sildenafil significantly reduced the frequency and duration of Raynaud's attacks, improved blood flow in the capillaries, and healed finger and toe ulcerations. Patients received either sildenafil or a placebo for 4 weeks and were then switched to the opposite treatment for an additional 4 weeks. Sildenafil-treated patients had an average of 35 Raynaud's attacks compared to 52 in placebo-treated patients (P = .0064). Moreover, the total duration of attacks were significantly shorter with sildenafil versus placebo (P = .0386).

During sildenafil treatment, average capillary blood flow velocity more than quadrupled, according to the study. Patients reported less pain and lesions began to heal in patients with chronic ulcerations on their fingers and toes.

"The [new study by Caglayan et al1] strongly supports our findings," Dr. Fries tells CIAOMed. "I think PDE5 inhibition in the future may be the first-line treatment for all patients with serious or complicated Raynaud´s phenomenon. As it will be the first treatment which works without significant side effects, it's a very important development," he says, adding that sildenafil will work in most, perhaps all, patients with RD, but since it is rather expensive, it should be chosen only for serious cases.

References

  1. Caglayan E, Huntgeburth M, Karasch T, et al. Phosphodiesterase type 5 inhibition is a novel therapeutic option in Raynaud disease. Arch Intern Med. 2006;166:231-233.
  2. Fries R, Shariat K, von Wilmowsky H, Böhm M. Sildenafil in the treatment of Raynaud's phenomenon resistant to vasodilatory therapy. Circulation. 2005;112:2980-2985.