Although there is a high probability that on-demand sildenafil is superior to placebo for the treatment of Raynaud phenomenon before exposure to cold, aggregated results and heterogeneous patient response did not indicate that the treatment had clinically relevant efficacy, according to a study published in the Annals of Internal Medicine.

Due to the risks for adverse effects, patients with Raynaud phenomenon may not be willing to be treated long-term with phosphodiesterase-5 inhibitors. Researchers in the current series of randomized, double-blind trials (ClinicalTrials.gov: NCT02050360) assessed the safety and efficacy of an on-demand, single dose of sildenafil before or during cold exposure for patients with primary or secondary Raynaud phenomenon at a French University hospital.

Each patient (n=38) received repeat blocks of on-demand treatment in 3 periods: 1 week of placebo, 1 week of 40 mg sildenafil, and 1 week of 80 mg sildenafil (maximum 2 doses per day). Results were assessed using frequency and duration of attacks, Raynaud Condition Score (RCS), and blood flow to the skin measured via laser speckle contrast imaging. Individual and aggregated efficacy were determined by mixed-effects models and parameters were estimated in a Bayesian framework.


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Study participants completed 2 to 5 blocks of treatment. Although the aggregated data showed a greater than 90% probability that both 40 mg and 80 mg doses of sildenafil were more effective than placebo for all outcomes (excepting RCS with 80 mg sildenafil), the aggregated effect size did not prove clinically relevant (adjusted relative variations ≥0.9 for all outcomes). Substantial heterogeneity in participant response did, however, show clinically relevant efficacy for some participants.

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Study investigators conclude that “these findings may justify sildenafil’s use as a second-line treatment in patients who do not want daily, long-term therapy with [calcium-channel blockers] or [phosphodiesterase-5] inhibitors.”

Disclosures: Partial funding for this study was provided by Pfizer.

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Reference

Roustit M, Giai J, Gaget O, et al. On-demand sildenafil as a treatment for Raynaud phenomenon: a series of n-of-1 trials [published online October 30, 2018]. Ann Intern Med.  doi: 10.7326/M18-0517