The certainty of the evidence is downgraded by inconsistency (statistical heterogeneity) and by imprecise results (few patients).
A Cochrane review [Abstract] 1 included 9 studies with a total of 411 subjects; majority had Raynaud's phenomenon secondary to systemic sclerosis. Phosphodiesterase 5 inhibitors (PDE5i; tadalafil 4 studies, sildenafil 3 studies, vardenafil 1 study, a new PDE5i known as PF-00489791 1 study) were compared with placebo. The durations of the studies varied from 4 to 8 weeks.
PDE5i reduced the frequency of attacks per week (24 vs. 21 attacks; MD -3.07, 95% CI -5.15 to -1.00; statistical heterogeneity I2 =74%; 8 studies, n=397) and the duration of attacks per day (55 minutes vs. 50 minutes; MD -5.31 minutes, 95% CI -8.90 to -1.71; statistical heterogeneity I2 =70%; 8 studies, n=397).
The severity of Raynaud's attacks (assessed on a 10 cm visual analogue scale, VAS, lower scores indicating less severity) was 20% lower with a PDE5i (3.7 with vs. 1.6; MD -2.05, 95% CI -2.68 to -1.42; 1 study, n=8).Pain and patient global assessment were assessed on a 10 cm VAS; lower scores indicating improvement. There was no difference in the average pain of Raynaud's attacks. Global scores were 36% lower with the use of a PDE5i compared to placebo (9.2 vs. 5.6; MD -3.59, 95% CI -4.45 to -2.73; 1 study, n=24).
The rate of withdrawals during treatment with PDE5i ranged from 4% to 20% compared with 2% in the placebo group in 5 studies, and 4 studies reported no withdrawals due to adverse events. Seven studies reported no serious adverse events. The rate of serious adverse events reported in 2 studies ranged from 2% during treatment to 4% with placebo.
All the included studies had a majority of participants with Raynaud's phenomenon secondary to systemic sclerosis. The test for subgroup differences between primary and secondary Raynaud's did not indicate a difference in the results between the 2 groups. Since secondary Raynaud's phenomenon (especially scleroderma) is more difficult to treat, PDE5i may be just as effective in the less severe primary Raynaud's phenomenon and Raynaud's phenomenon secondary to other connective diseases.
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