The quality of evidence is downgraded by study quality (unclear allocation concealmentand blinding), by inconsistency (heterogeneity in interventions and outcomes) and by imprecise results (few patients and wide confidence intervals).
A Cochrane review [Abstract] 1 included 15 studies with a total of 635 subjects comparing different vasodilators to placebo.
Angiotensin converting enzyme (ACE) inhibitors:A small increase in the frequency of attacks per week after treatment (captopril or enalapril) compared to placebo (MD 0.79, 95% CI 0.43 to 1.17; 3 studies, n=44) was observed. There was no evidence of a difference between groups in severity of attacks, duration of attacks or adverde events (AEs). Alpha blockers:Two studies used alpha blockers (buflomedil or moxisylyte). Buflomedil reduced the frequency of attacks compared to placebo (MD -8.82, 95% CI -11.04 to -6.60; 1 study, n=31) and improved severity scores (MD -0.41, 95% CI -0.62 to -0.30). Moxisylyte was associated with fewer attacks (P < 0.02), less severe symptoms (P < 0.01), and shorter duration of attacks, but the clinical relevance of these results was unclear. There was no difference in AEs between buflomedil and placebo. More AEs were observed in the moxisylyte group compared to placebo.Prostaglandin/prostacyclin analogues:There was no evidence of benefit for frequency (MD 2.00, 95% CI -0.35 to 4.35; 1 study, n=118) or severity (MD -0.06, 95% CI -0.34 to 0.22), but more AEs were in the beraprost group (RR 1.59, 95% CI 1.05 to 2.42; 1 study, n=125) compared to placebo. Thromboxane synthase inhibitors: Dazoxiben did not reduce the frequency of attacks (MD 0.8, 95% CI -1.81 to 3.41; 1 study, n=6) compared to placebo. Selective serotonin reuptake inhibitors:There was a slight reduction in the number of attacks per week (MD -14.0, 95% CI -27.72 to -0.28; 1 study, n=41) and in the severity score (MD -133.00, 95% CI -162.40 to -103.60) with ketanserin compared to placebo. Ketanserin did not reduce the duration of attacks and there was no difference in the AEs. Nitrate/nitrate derivativesFour studies compared topical treatments of nitroglycerin or glyceryl trinitrate versus placebo. There was no evidence of effect on frequency of attacks per week (MD -1.57, 95% CI -4.31 to 1.17; 2 studies, n=86). Phosphodiesterase inhibitorsThree studies compared phosphodiesterase inhibitors (vardenafil, cilostazol or PF-00489791) to placebo. There was no difference in frequency of attacks (SMD -0.05, 95% CI -6.71 to 6.61; 2 studies, n=111), severity of attacks, or duration of attacks. 35% of participants on cilostazol complained of headaches. PF-00489791 caused 34 of 54 participants to experience AEs versus 43/102 in placebo group; headache was most common.
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