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BMJ Clinical Evidence Sep 2008Raynaud's phenomenon is episodic vasospasm of the peripheral vessels, causing pallor followed by cyanosis and redness with pain and sometimes paraesthesia, and, rarely,... (Review)
Review
INTRODUCTION
Raynaud's phenomenon is episodic vasospasm of the peripheral vessels, causing pallor followed by cyanosis and redness with pain and sometimes paraesthesia, and, rarely, ulceration of the fingers and toes. It presents as episodic colour changes of the digits, usually in response to cold exposure or stress. The classic triphasic colour change is white (ischaemia), then blue (deoxygenation), then red (reperfusion). Raynaud's phenomenon can be primary (idiopathic) or secondary to several different conditions and causes. This review deals with secondary Raynaud's phenomenon.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of self-help measures for secondary Raynaud's phenomenon? What are the effects of drug treatments for secondary Raynaud's phenomenon? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2007 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 25 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: alpha-blockers; angiotensin-converting enzyme (ACE) inhibitors; angiotensin II receptor antagonists; antithrombotics/inhibitors of platelet aggregation; biofeedback; calcium channel blockers; endothelin-1 receptor anatagonists; glyceryl trinitrate (transdermal); hand exercises; inositol nicotinate; moxisylyte; nafitidrofuryl oxylate; phosphodiesterase inhibitors; prostaglandins (oral, intravenous); relaxation therapy; serotonin reuptake inhibitors SRIs; smoking cessation; and warming hands and feet.
Topics: Administration, Oral; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Endothelin Receptor Antagonists; Humans; Phosphodiesterase Inhibitors; Raynaud Disease; Receptor, Endothelin A
PubMed: 19445801
DOI: No ID Found -
BMJ Clinical Evidence Dec 2008Raynaud's phenomenon is an episodic vasospasm of the peripheral arteries, causing pallor followed by cyanosis and redness with pain and sometimes paraesthesia. On rare... (Review)
Review
INTRODUCTION
Raynaud's phenomenon is an episodic vasospasm of the peripheral arteries, causing pallor followed by cyanosis and redness with pain and sometimes paraesthesia. On rare occasions it can lead to ulceration of the fingers and toes (and in some cases of the ears or nose). This review focuses on primary (idiopathic) Raynaud's phenomenon occurring in the absence of an underlying disease. The prevalence of primary Raynaud's phenomenon varies by sex, country, and exposure to workplace vibration.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for primary Raynaud's phenomenon? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2008 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 15 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: amlodipine, diltiazem, exercise, inositol nicotinate, keeping warm, moxisylyte (thymoxamine), naftidrofuryl oxalate, nicardipine, nifedipine, prazosin, and smoking cessation.
Topics: Administration, Oral; Humans; Nifedipine; Prevalence; Raynaud Disease; Ulcer; Vibration
PubMed: 19445785
DOI: No ID Found -
The Cochrane Database of Systematic... Oct 2007Secondary ischaemia is a frequent cause of poor outcome in patients with aneurysmal subarachnoid haemorrhage (SAH). Besides vasospasm, platelet aggregation seems to play... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Secondary ischaemia is a frequent cause of poor outcome in patients with aneurysmal subarachnoid haemorrhage (SAH). Besides vasospasm, platelet aggregation seems to play a role in the pathogenesis of secondary ischaemia. Experimental studies have suggested that antiplatelet agents can prevent secondary ischaemia.
OBJECTIVES
To determine whether antiplatelet agents change outcome in patients with aneurysmal SAH.
SEARCH STRATEGY
We searched the Cochrane Stroke Group Trials Register (last searched August 2006), MEDLINE (1966 to August 2006) and EMBASE databases (1980 to August 2006). We also searched reference lists of identified trials.
SELECTION CRITERIA
All randomised controlled trials (RCTs) comparing any antiplatelet agent with control in patients with aneurysmal SAH.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted the data and assessed trial quality. Relative risks (RR) were calculated with regard to poor outcome, case fatality, secondary ischaemia, haemorrhagic intracranial complications and aneurysmal rebleeding according to the intention-to-treat principle. In case of a statistically significant primary analysis, a worst case analysis was performed.
MAIN RESULTS
Seven RCTs were included in the review, totalling 1385 patients. Four of these trials met the criteria for good quality studies. For any antiplatelet agent there were reductions of a poor outcome (RR 0.79, 95% confidence interval (CI) 0.62 to 1.01) and secondary brain ischaemia (RR 0.79, 95% CI 0.56 to 1.22) and more intracranial haemorrhagic complications (RR 1.36, 95% CI 0.59 to 3.12), but none of these differences were statistically significant. There was no effect on case fatality (RR 1.01, 95% CI 0.74 to 1.37) or aneurysmal rebleeding (RR 0.98, 95% CI 0.78 to 1.38). For individual antiplatelet agents, only ticlopidine was associated with statistically significant fewer occurrences of a poor outcome (RR 0.37, 95% CI 95% CI 0.14 to 0.98) but this estimate was based on only one small RCT.
AUTHORS' CONCLUSIONS
This review shows a trend towards better outcome in patients treated with antiplatelet agents, possibly due to a reduction in secondary ischaemia. However, results were not statistically significant, thus no definite conclusions can be drawn. Also, antiplatelet agents could increase the risk of haemorrhagic complications. On the basis of the current evidence treatment with antiplatelet agents in order to prevent secondary ischaemia or poor outcome cannot be recommended.
Topics: Brain Ischemia; Humans; Intracranial Aneurysm; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Subarachnoid Hemorrhage; Treatment Outcome
PubMed: 17943892
DOI: 10.1002/14651858.CD006184.pub2 -
Clinical Cardiology May 2008Takotsubo cardiomyopathy typically presents with chest pain, ST changes, and transient left ventricular apical ballooning in the absence of epicardial coronary artery... (Review)
Review
Takotsubo cardiomyopathy typically presents with chest pain, ST changes, and transient left ventricular apical ballooning in the absence of epicardial coronary artery disease. This process is reversible and usually benign. An unusual manifestation is that of left ventricular outflow tract obstruction with systolic anterior motion of the mitral valve. Recognition of this finding is critical in patient management especially in the setting of cardiogenic shock, as inotropes are likely to aggravate and worsen the clinical condition. We provide a systematic review and an illustrative case and discuss treatment strategies.
Topics: Aged; Coronary Vasospasm; Female; Humans; Mitral Valve Insufficiency; Takotsubo Cardiomyopathy; Ventricular Outflow Obstruction
PubMed: 17847035
DOI: 10.1002/clc.20212 -
The Cochrane Database of Systematic... Jul 2007Secondary ischaemia is a frequent cause of poor outcome in patients with subarachnoid haemorrhage (SAH). Its pathogenesis has been incompletely elucidated, but vasospasm... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Secondary ischaemia is a frequent cause of poor outcome in patients with subarachnoid haemorrhage (SAH). Its pathogenesis has been incompletely elucidated, but vasospasm probably is a contributing factor. Experimental studies have suggested that calcium antagonists can prevent or reverse vasospasm and have neuroprotective properties.
OBJECTIVES
To determine whether calcium antagonists improve outcome in patients with aneurysmal SAH.
SEARCH STRATEGY
We searched the Cochrane Stroke Group Trials Register (last searched April 2006), MEDLINE (1966 to March 2006) and EMBASE (1980 to March 2006). We handsearched two Russian journals (1990 to 2003), and contacted trialists and pharmaceutical companies in 1995 and 1996.
SELECTION CRITERIA
Randomised controlled trials comparing calcium antagonists with control, or a second calcium antagonist (magnesium sulphate) versus control in addition to another calcium antagonist (nimodipine) in both the intervention and control groups.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted the data and assessed trial quality. Trialists were contacted to obtain missing information.
MAIN RESULTS
Sixteen trials, involving 3361 patients, were included in the review; three of the studies were of magnesium sulphate in addition to nimodipine. Overall, calcium antagonists reduced the risk of poor outcome: the relative risk (RR) was 0.81 (95% confidence interval (CI) 0.72 to 0.92); the corresponding number of patients needed to treat was 19 (95% CI 1 to 51). For oral nimodipine alone the RR was 0.67 (95% CI 0.55 to 0.81), for other calcium antagonists or intravenous administration of nimodipine the results were not statistically significant. Calcium antagonists reduced the occurrence of secondary ischaemia and showed a favourable trend for case fatality. For magnesium in addition to standard treatment with nimodipine, the RR was 0.75 (95% CI 0.57 to 1.00) for a poor outcome and 0.66 (95% CI 0.45 to 0.96) for clinical signs of secondary ischaemia.
AUTHORS' CONCLUSIONS
Calcium antagonists reduce the risk of poor outcome and secondary ischaemia after aneurysmal SAH. The results for 'poor outcome' depend largely on a single large trial of oral nimodipine; the evidence for other calcium antagonists is inconclusive. The evidence for nimodipine is not beyond all doubt, but given the potential benefits and modest risks of this treatment, oral nimodipine is currently indicated in patients with aneurysmal SAH. Intravenous administration of calcium antagonists cannot be recommended for routine practice on the basis of the present evidence. Magnesium sulphate is a promising agent but more evidence is needed before definite conclusions can be drawn.
Topics: Calcium Channel Blockers; Humans; Intracranial Aneurysm; Nimodipine; Randomized Controlled Trials as Topic; Subarachnoid Hemorrhage; Treatment Outcome
PubMed: 17636626
DOI: 10.1002/14651858.CD000277.pub3 -
The Cochrane Database of Systematic... 2000Acute traumatic brain injury is a major cause of death and disability. Calcium channel blockers have been used in an attempt to prevent cerebral vasospasm after injury,... (Review)
Review
BACKGROUND
Acute traumatic brain injury is a major cause of death and disability. Calcium channel blockers have been used in an attempt to prevent cerebral vasospasm after injury, maintain blood flow to the brain and so prevent further damage.
OBJECTIVES
To estimate the effects of calcium channel blockers in patients with acute traumatic brain injury and in a subgroup of brain injury patients with traumatic subarachnoid haemorrhage.
SEARCH STRATEGY
Hand searching and electronic searching for randomized controlled trials available by October 1997.
SELECTION CRITERIA
Randomized controlled trials in patients with all levels of severity of clinically diagnosed acute traumatic brain injury.
DATA COLLECTION AND ANALYSIS
Two reviewers (JL and CG) independently assessed the identified studies for eligibility and extracted data from each study. Summary odds ratios were calculated using the Mantel-Haenszel method.
MAIN RESULTS
Four RCTs were identified as eligible for inclusion in the systematic review. The effect of calcium channel blockers on the risk of death was reported in all RCTs. The pooled odds ratio for the four studies was 0.91 (95% confidence interval 0. 70 to 1.17). For the three RCTs that reported death and severe disability the pooled odds ratio was 0.85 (95% CI 0.68 to 1.07). In the two RCTs which reported the risk of death in a sub group of traumatic subarachnoid haemorrhage patients, the pooled odds ratio was 0.59 (95% CI 0.37 to 0.94). Three RCTs reported death and severe disability as an outcome in this subgroup, and the pooled odds ratio was 0.67 (95% CI 0.46 to 0.98).
REVIEWER'S CONCLUSIONS
This systematic review of randomized controlled trials of calcium channel blockers in acute traumatic head injury patients shows that considerable uncertainty remains over their effects. The effect of nimodipine in a subgroup of brain injury patients with subarachnoid haemorrhage shows a beneficial effect, though the increase in adverse reactions suffered by the intervention group may mean that the drug is harmful for some patients.
Topics: Brain Injuries; Calcium Channel Blockers; Humans; Subarachnoid Hemorrhage; Vasospasm, Intracranial
PubMed: 10796727
DOI: 10.1002/14651858.CD000565 -
The Cochrane Database of Systematic... 2000To determine the effects and toxicity of prazosin versus placebo proposed for the treatment of Raynaud's phenomenon (RP) in scleroderma. (Review)
Review
OBJECTIVES
To determine the effects and toxicity of prazosin versus placebo proposed for the treatment of Raynaud's phenomenon (RP) in scleroderma.
SEARCH STRATEGY
We searched the Cochrane Controlled Trials Register, and Medline up to December 1996 using the Cochrane Collaboration search strategy developed by Dickersin et al.(1994). Key words included: Raynaud's or vasospasm, scleroderma or progressive systemic sclerosis or connective tissue disease or autoimmune disease. Current Contents were searched up to and including April 7, 1997. All bibliographies of articles retrieved were searched and key experts in the area were contacted for additional and unpublished data. The initial search strategy included all languages.
SELECTION CRITERIA
Randomized controlled trials comparing prazosin versus placebo were eligible if they reported clinical outcomes from the start of therapy. Trials with a greater than 35% dropout were excluded. Trials were included if patients with diffuse or limited scleroderma were the subjects. If patients with other connective tissue diseases or primary Raynaud's were included, the trial was used if the data on the scleroderma patients could be extracted from the paper.
DATA COLLECTION AND ANALYSIS
All data were abstracted by two independent and trained reviewers (DF, AT), and verified by a third reviewer (JP). Each trial was assessed independently by the same two reviewers for its quality using a validated quality assessment tool (Jadad 1996). Peto's odds ratios were calculated for all dichotomous outcomes and a weighted mean difference was carried out on all continuous outcomes. Fixed effects and random effects model were used if the data was homogeneous or heterogeneous, respectively.
MAIN RESULTS
Two trials with a total of 40 patients were included. Prazosin has been found in two randomized controlled cross-over trials to be more effective than placebo in the treatment of Raynaud's secondary to scleroderma. However, the positive response is modest and side effects are not rare in those taking prazosin.
REVIEWER'S CONCLUSIONS
Prazosin is modestly effective in the treatment of Raynaud's phenomenon secondary to scleroderma.
Topics: Adrenergic alpha-Antagonists; Humans; Prazosin; Raynaud Disease; Scleroderma, Systemic
PubMed: 10796398
DOI: 10.1002/14651858.CD000956 -
The Cochrane Database of Systematic... 2000To assess the effects and toxicity of Cyclofenil versus placebo for the treatment of Raynaud's phenomenon (RP) in scleroderma. (Review)
Review
OBJECTIVES
To assess the effects and toxicity of Cyclofenil versus placebo for the treatment of Raynaud's phenomenon (RP) in scleroderma.
SEARCH STRATEGY
We searched the Cochrane Controlled Trials Register, and Medline up to 1996 using the Cochrane Collaboration search strategy developed by Dickersin et al.(1994). Key words included: Raynaud's or Vasospasm, Scleroderma or Progressive Systematic Sclerosis or Connective Tissue Disease or Autoimmune Disease. Current Contents were searched up to and including April 7, 1997. All bibliographies of articles retrieved were searched and key experts in the area were contacted for additional and unpublished data. The initial search strategy included all languages.
SELECTION CRITERIA
All randomized trials comparing cyclofenil versus placebo were eligible if they reported any clinical outcomes within the trial.
DATA COLLECTION AND ANALYSIS
Data were abstracted independently by two reviewers (DF, AT). Peto's odds ratio (OR) was calculated for all dichotomous outcomes, and a weighted mean difference was calculated for all continuous outcomes. A fixed effects or random effects model was used if the data were homogeneous or heterogeneous respectively.
MAIN RESULTS
One trial with 38 patients was included. There was a trend for Cyclofenil to demonstrate more improvement and more dropouts compared to placebo, but there were no statistically significant differences.
REVIEWER'S CONCLUSIONS
Cyclofenil is not effective in the treatment of Raynaud's phenomenon secondary to scleroderma.
Topics: Cyclofenil; Humans; Raynaud Disease; Scleroderma, Systemic
PubMed: 10796397
DOI: 10.1002/14651858.CD000955 -
The Cochrane Database of Systematic... 2000To assess the effects and toxicity of the following agent: ketanserin versus placebo proposed for the treatment of Raynaud's phenomenon (RP) in scleroderma. (Review)
Review
OBJECTIVES
To assess the effects and toxicity of the following agent: ketanserin versus placebo proposed for the treatment of Raynaud's phenomenon (RP) in scleroderma.
SEARCH STRATEGY
We searched the Cochrane Controlled Trials Register, and Medline up to 1996 using the Cochrane Collaboration search strategy developed by Dickersin et al.(1994). Key words included: Raynaud's or vasospasm, scleroderma or progressive systematic sclerosis or connective tissue disease or autoimmune disease. Current Contents were searched up to and including April 7, 1997. All bibliographies of articles retrieved were searched and key experts in the area were contacted for additional and unpublished data. The initial search strategy included all languages.
SELECTION CRITERIA
All randomized controlled trials comparing ketanserin versus placebo were eligible if they reported clinical outcomes of interest. Trials with dropout rates greater than 35% were excluded.
DATA COLLECTION AND ANALYSIS
Data were abstracted independently by two reviewers (DF, AT). Peto's odds ratios (OR) were calculated for all dichotomous outcomes, and a weighted mean difference (WMD) was carried out on all continuous outcomes. A fixed effects or random effects model were used if the data was homogeneous or heterogeneous, respectively.
MAIN RESULTS
Three trials and 66 patients were included. The proportion improved was significantly better in the group on ketanserin with an odds ratio (OR) of 4.80 (95% CI 1.33, 17.37). However, when comparing ketanserin to placebo, the decrease in severity of RP attacks favoured placebo but this was not statistically significant. Side effects were significantly more common in the group using active treatment with an OR of 5.96 (95% CI 1.61, 22.06). Frequency of attacks did not change, but the duration of attacks decreased significantly in the ketanserin group.
REVIEWER'S CONCLUSIONS
Ketanserin may have some efficacy in the treatment of Raynaud's phenomenon secondary to scleroderma. Overall, ketanserin is not significantly different from placebo for the treatment of Raynaud's phenomenon except for some decrease in the duration of attacks and more subjects improved on ketanserin compared to placebo. However, there were more side effects. It can be concluded that ketanserin treatment in Raynaud's phenomenon secondary to scleroderma is not clinically beneficial.
Topics: Humans; Ketanserin; Raynaud Disease; Scleroderma, Systemic; Serotonin Antagonists
PubMed: 10796396
DOI: 10.1002/14651858.CD000954 -
The Cochrane Database of Systematic... 2000To assess the effects and toxicity of the following agents:Prostaglandin analogues together with other agents proposed for the treatment of Raynaud's phenomenom (RP) in... (Review)
Review
OBJECTIVES
To assess the effects and toxicity of the following agents:Prostaglandin analogues together with other agents proposed for the treatment of Raynaud's phenomenom (RP) in scleroderma.
SEARCH STRATEGY
We searched the Cochrane Controlled Trials Register, and Medline up to 1996 using the Cochrane Collaboration search strategy developed by Dickersin et al.(1994). Key words included: raynaud's or vasospasm, scleroderma or progressive systemic sclerosis or connective tissue disease or autoimmune disease. Current Contents were searched up to and including April 7, 1997. All bibliographies of articles retrieved were searched and key experts in the area were contacted for additional and unpublished data. The initial search strategy included all languages.
SELECTION CRITERIA
All randomized controlled trials comparing prostaglandin analogues versus placebo were eligible if they reported clinical outcomes within the start of therapy, and if the dropout rate was less than 35%.
DATA COLLECTION AND ANALYSIS
Data were abstracted independently by two reviewers (DF, AT). Peto's odds ratios were calculated for all dichotomous outcomes and a weighted mean difference was calculated for all continuous outcomes. A fixed effects or random effects model was used if the data were homogeneous or heterogeneous, respectively.
MAIN RESULTS
Seven randomized trials and 332 patients were included. Five of the seven trials were of parallel design. Five trials compared I.V. Iloprost and one trial studied p.o. Iloprost and another p.o. Cisaprost. Some trials were dose finding trials so various doses of Iloprost were used. Due to different efficacies of I.V. Iloprost, oral Iloprost and oral Cisaprost, the overall efficacy of these drugs was somewhat diluted. Intravenous Iloprost appears to be effective in the treatment of secondary Raynaud's phenomenon.
REVIEWER'S CONCLUSIONS
Intravenous Iloprost is effective in the treatment of Raynaud's phenomenon secondary to scleroderma at decreasing the frequency and severity of attacks and preventing or healing digital ulcers. The effect seems to be prolonged after the intravenous infusion is given. Oral Iloprost may have less efficacy than intravenous Iloprost. However, Cisaprost has minimal or no efficacy when given orally for the treatment of Raynaud's phenomenon secondary to scleroderma.
Topics: Humans; Iloprost; Raynaud Disease; Scleroderma, Systemic; Vasodilator Agents
PubMed: 10796395
DOI: 10.1002/14651858.CD000953