Phosphodiesterase-5 inhibitors appear to reduce the daily frequency of ischemic attacks in secondary Raynaud’s phenomenon to a significant degree, amounting to a decrease of nearly 0.5 attacks per day, according to a meta-analysis of trials.
The study also revealed significant but moderate effects of the phosphodiesterase-5 (PDE-5) inhibitors on the Raynaud’s Condition Score (RCS) and attack duration, but the class effect of PDE-5 inhibitors in secondary Raynaud’s phenomenon (RP) needs to be clarified through additional studies because differences between the trials made it difficult to come to clear conclusions, according to Matthieu Roustit, Pharm.D., Ph.D., of Joseph Fourier University, Grenoble, France, and his colleagues.
The investigators searched the Cochrane, Medline, Embase, and Web of Sciences databases for double-blind, randomized, controlled trials of PDE-5 inhibitors in secondary RP (Ann. Rheum. Dis. 2013 Feb. 20 [doi:10.1136/annrheumdis-2012-202836]).
They also looked for these trials in abstracts from meetings of the European League Against Rheumatism and the American College of Rheumatology, as well as in listings at the clinicaltrials.gov site.
In the final analysis, the investigators included six double-blind, randomized, placebo-controlled trials involving 244 patients – one with sildenafil (Viagra), one with modified-release sildenafil, three with tadalafil (Cialis), and one with vardenafil (Levitra). They excluded patients with primary Raynaud’s.
Most patients (91.8%) had RP secondary to systemic sclerosis; the remainder had mixed or undifferentiated connective tissue disease.
Only two trials allowed the use of other vasodilators, both of which tested tadalafil as an add-on to calcium channel blockers, although another study that tested tadalafil monotherapy for RP allowed seven patients to take calcium channel blockers and eight patients to take angiotensin-converting enzyme inhibitors for other indications.
Dr. Roustit and his associates found that the use of PDE-5 inhibitors significantly reduced the mean RCS by -0.46 (95% confidence interval -0.74 to -0.17; P = .002).
The drugs also reduced the frequency of attacks by -0.49 per day (95% CI, -0.71 to -0.28; P less than .0001), although this improvement fell beneath the minimally significant difference on the RCS, which is estimated to be 1.4-1.5 attacks per day.
PDE-5 inhibitors lessened the daily duration of attacks by 14.62 minutes (95% CI, -20.25 to -9.00; P less than .0001).
According to the authors, the decrease in number of attacks per day echoes the finding of another study assessing the efficacy of calcium channel blockers in secondary RP, which calculated a reduction of roughly 0.6 attacks per day (Arthritis Rheum. 2001;44:1841-7).
They added, however, that some data have also found PDE-5 inhibitors to be associated with reduction of digital ischemic ulcers in secondary Raynaud’s, although "data are scarce, and larger RCTs are ongoing to address this issue."
Dr. Roustit and another investigator disclosed receiving research grants from Pfizer (which markets sildenafil), Actelion, GlaxoSmithKline (which markets vardenafil) and Bioprojet for other studies. A third investigator disclosed receiving research grants and honoraria from Pfizer and Actelion for other studies.