Pharmacological treatment for buerger's disease
Data
2016
Autores
Cacione, Daniel G. 
Macedo, Cristiane R.
Baptista-Silva, Jose C. C.
Tipo
Revisão
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Background Buerger's disease (thromboangiitis obliterans) is a non-atherosclerotic, segmental inflammatory pathology that most commonly affects the small and medium sized arteries, veins, and nerves in the upper and lower extremities. The etiology is unknown, but involves hereditary susceptibility, tobacco exposure, immune and coagulation responses. In many cases, there is no possibility of revascularization to improve the condition. Pharmacological treatment is an option for patients with severe complications, such as ischaemic ulcers or rest pain. Objectives To assess the effectiveness of any pharmacological agent (intravenous or oral) compared with placebo or any other pharmacological agent in patients with Buerger's disease. Search methods The Cochrane Vascular Trials Search Co-ordinator searched their Specialised Register (last searched in April 2015) and the Cochrane Register of Studies (Issue 3, 2015). The review authors searched trial registers and the European grey literature
screened reference lists of relevant studies, and contacted study authors and major pharmaceutical companies. Selection criteria Randomised controlled trials (RCTs) involving pharmacological agents used in the treatment of Buerger's disease. Data collection and analysis Two review authors, independently assessed the studies, extracted data and performed data analysis. Main results Five randomised controlled trials (total 602 participants) compared prostacyclin analogue with placebo, aspirin, or a prostaglandin analogue, and folic acid with placebo. No studies assessed other pharmacological agents such as cilostazol, clopidogrel and pentoxifylline or compared oral versus intravenous prostanoid. Compared with aspirin, intravenous prostacyclin analogue iloprost improved ulcer healing (risk ratio (RR) 2.65
95% confidence interval (CI) 1.15 to 6.11
98 participants
one study
moderate quality evidence), and helped to eradicate rest pain after 28 days (RR 2.28
95% CI 1.48 to 3.52
133 participants
one study
moderate quality evidence), although amputation rates were similar six months after treatment (RR 0.32
95% CI 0.09 to 1.15
95 participants
one study
moderate quality evidence). When comparing prostacyclin (iloprost and clinprost) with prostaglandin (alprostadil) analogues, ulcer healing was similar (RR 1.13
95% CI 0.76 to 1.69
89 participants
two studies
I-2 = 0%
very low quality evidence), as was the eradication of rest pain after 28 days (RR 1.57
95% CI 0.72 to 3.44
38 participants
one study
low quality evidence), while amputation rates were not measured. Compared with placebo, the effects of oral prostacyclin analogue iloprost were similar for: healing ischaemic ulcers (iloprost 200 mcg: RR 1.11
95% CI 0.54 to 2.29
133 participants
one study
moderate quality evidence, and iloprost 400 mcg: RR 0.90
95% CI 0.42 to 1.93
135 participants
one study
moderate quality evidence), eradication of rest pain after eight weeks (iloprost 200 mcg: RR 1.14
95% CI 0.79 to 1.63
207 participants
one study
moderate quality evidence, and iloprost 400 mcg: RR 1.11
95% CI 0.77 to 1.59
201 participants
one study
moderate quality evidence), and amputation rates after six months (iloprost 200 mcg: RR 0.54
95% CI 0.19 to 1.56
209 participants
one study, and iloprost 400 mcg: RR 0.42
95% CI 0.13 to 1.31
213 participants
one study). When comparing folic acid with placebo in patients with Buerger's disease and hyperhomocysteinaemia, pain scores were similar, there were no new cases of amputation in either group, and ulcer healing was not assessed (very low quality evidence). Treatment side effects such as headaches, flushing or nausea were not associated with treatment interruptions or more serious consequences. Outcomes such as amputation-free survival, walking distance or pain-free walking distance, and ankle brachial index were not assessed by any study. Overall, the quality of the evidence was very low to moderate, with few studies, small numbers of participants, variation in severity of disease of participants between studies and missing information regarding for example baseline tobacco exposure. Authors' conclusions Moderate quality evidence suggests that intravenous iloprost (prostacyclin analogue) is more effective than aspirin for eradicating rest pain and healing ischaemic ulcers in Buerger's disease, but oral iloprost is not more effective than placebo. Verylow and low quality evidence suggests there is no difference between prostacyclin (iloprost and clinprost) and the prostaglandin analogue alprostadil for healing ulcers and relieving pain respectively in severe Buerger's disease. Very-low quality evidence suggests there is no difference in pain scores and amputation rates between folic acid and placebo, in people with Buerger's disease and hyperhomocysteinaemia. High quality trials assessing the effectiveness of pharmacological agents (intravenous or oral) in people with Buerger's disease are needed.
screened reference lists of relevant studies, and contacted study authors and major pharmaceutical companies. Selection criteria Randomised controlled trials (RCTs) involving pharmacological agents used in the treatment of Buerger's disease. Data collection and analysis Two review authors, independently assessed the studies, extracted data and performed data analysis. Main results Five randomised controlled trials (total 602 participants) compared prostacyclin analogue with placebo, aspirin, or a prostaglandin analogue, and folic acid with placebo. No studies assessed other pharmacological agents such as cilostazol, clopidogrel and pentoxifylline or compared oral versus intravenous prostanoid. Compared with aspirin, intravenous prostacyclin analogue iloprost improved ulcer healing (risk ratio (RR) 2.65
95% confidence interval (CI) 1.15 to 6.11
98 participants
one study
moderate quality evidence), and helped to eradicate rest pain after 28 days (RR 2.28
95% CI 1.48 to 3.52
133 participants
one study
moderate quality evidence), although amputation rates were similar six months after treatment (RR 0.32
95% CI 0.09 to 1.15
95 participants
one study
moderate quality evidence). When comparing prostacyclin (iloprost and clinprost) with prostaglandin (alprostadil) analogues, ulcer healing was similar (RR 1.13
95% CI 0.76 to 1.69
89 participants
two studies
I-2 = 0%
very low quality evidence), as was the eradication of rest pain after 28 days (RR 1.57
95% CI 0.72 to 3.44
38 participants
one study
low quality evidence), while amputation rates were not measured. Compared with placebo, the effects of oral prostacyclin analogue iloprost were similar for: healing ischaemic ulcers (iloprost 200 mcg: RR 1.11
95% CI 0.54 to 2.29
133 participants
one study
moderate quality evidence, and iloprost 400 mcg: RR 0.90
95% CI 0.42 to 1.93
135 participants
one study
moderate quality evidence), eradication of rest pain after eight weeks (iloprost 200 mcg: RR 1.14
95% CI 0.79 to 1.63
207 participants
one study
moderate quality evidence, and iloprost 400 mcg: RR 1.11
95% CI 0.77 to 1.59
201 participants
one study
moderate quality evidence), and amputation rates after six months (iloprost 200 mcg: RR 0.54
95% CI 0.19 to 1.56
209 participants
one study, and iloprost 400 mcg: RR 0.42
95% CI 0.13 to 1.31
213 participants
one study). When comparing folic acid with placebo in patients with Buerger's disease and hyperhomocysteinaemia, pain scores were similar, there were no new cases of amputation in either group, and ulcer healing was not assessed (very low quality evidence). Treatment side effects such as headaches, flushing or nausea were not associated with treatment interruptions or more serious consequences. Outcomes such as amputation-free survival, walking distance or pain-free walking distance, and ankle brachial index were not assessed by any study. Overall, the quality of the evidence was very low to moderate, with few studies, small numbers of participants, variation in severity of disease of participants between studies and missing information regarding for example baseline tobacco exposure. Authors' conclusions Moderate quality evidence suggests that intravenous iloprost (prostacyclin analogue) is more effective than aspirin for eradicating rest pain and healing ischaemic ulcers in Buerger's disease, but oral iloprost is not more effective than placebo. Verylow and low quality evidence suggests there is no difference between prostacyclin (iloprost and clinprost) and the prostaglandin analogue alprostadil for healing ulcers and relieving pain respectively in severe Buerger's disease. Very-low quality evidence suggests there is no difference in pain scores and amputation rates between folic acid and placebo, in people with Buerger's disease and hyperhomocysteinaemia. High quality trials assessing the effectiveness of pharmacological agents (intravenous or oral) in people with Buerger's disease are needed.
Descrição
Citação
Cochrane Database Of Systematic Reviews. Hoboken, n. 3, p. CD011033, 2016.