Vardenafil is a medicine approved by the U.S. Food and Drug Administration (FDA) to treat erectile dysfunction.

Because it works to relax the muscles of blood vessels and improve blood flow, it can also be used to treat two conditions commonly associated with systemic scleroderma:  Raynaud’s phenomenon, which is caused by the constriction of the small blood vessels in the hands and feet, cutting off circulation, and pulmonary arterial hypertension (PAH), or high blood pressure in the arteries of the lungs.

How vardenafil works

Scleroderma is an autoimmune disease in which the immune system mistakenly attacks connective tissue in the skin and other organs, causing scar tissue to form that can interfere with how these organs function. In blood vessels, scar tissue can cause stiffening and constriction. In Raynaud’s phenomenon, it can restrict blood flow to the fingers and toes,  causing sores or lesions to form on fingers and toes. In PAH, the formation of scar tissue causes stiffening of the blood vessels in the lungs and heart, increasing blood pressure and making breathing difficult, and raising a risk of heart failure.

Vardenafil inhibits an enzyme called PDE-5, whose role is to break down a signaling molecule called cyclic GMP (cGMP). cGMP normally relaxes smooth muscles, such as those that surround blood vessels, through a pathway called the cGMP pathway.

The chemical structure of vardenafil is very similar to that of cGMP so that it can bind to PDE-5, but it cannot be broken down by the enzyme. PDE-5 enzymes bound to vardenafil is not available to break down cGMP. This block on the enzyme’s action prolongs the chemical life of cGMP, relaxing the smooth muscles in blood vessels, which, in turn, lowers blood pressure in the lungs and increases blood flow to hands and feet.

Vardenafil in clinical trials

The effects of vardenafil on the clinical symptoms and peripheral blood flow in patients with Raynaud’s phenomenon were assessed in a double-blinded, placebo-controlled Phase 2/3 clinical trial (NCT01291199). A total of 53 patients with Raynaud’s phenomenon (89 percent with scleroderma-associated Raynaud’s) were treated with either 10 mg of vardenafil or placebo twice a day for six weeks. Primary outcomes measured were Raynaud condition score, a self-assessment test, and blood flow to fingertips measured by a laser Doppler perfusion imager, where a small device placed on a fingertip uses a laser to determine blood flow.

Trial results, published in the Archives of Internal Medicine in 2006, showed that treatment “significantly improves peripheral blood flow” and lowered the number of Raynaud’s attacks.

A Phase 3 clinical trial (NCT00718952) evaluated the safety and efficacy of treating PAH patients, including some whose disease was related to scleroderma, with 5 mg of oral vardenafil or a placebo, given once daily for four weeks and then twice a day for another eight weeks. This double-blind phase was followed by an open-label period where all 66 patients were treated for another 12 weeks with 5 mg of vardenafil twice daily. The researchers measured treatment efficacy by changes in the distance patients could walk in six minutes (the six-minute walk test), a measure of aerobic capacity and endurance. Blood vessel resistance near the heart was measured by cardiac catheterization where a long, flexible tube is threaded through a blood vessel into the heart.

Results were published in the American Journal of Respiratory and Critical Care Medicine in 2011 and showed that patients on vardenafil in the study’s double-blind phase improved in distance walked in the six-minute walking test relative to those on placebo, with improvements maintained through 24 weeks. They also showed a decrease in blood vessel resistance and pressure, indicating improved heart health as a result of treatment. The researchers concluded that  vardenafil was “effective and well tolerated in patients with PAH” at the dose studied.

Other information

Possible side effects of vardenafil use include headaches, upset stomach, flushing, and flu-like symptoms.

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