CRD summary

This review assessed the effect of nitric oxide donors on systemic haemodynamic measures in patients with acute or sub-acute stroke. The authors concluded that glyceryl trinitrate reduces blood-pressure and pulse pressure, whilst increasing the heart rate. The reliability of the conclusions is uncertain given the poor reporting of the review process and the limitations of the included studies.

Authors' objectives

To assess the effect of nitric oxide (NO) donors on systemic haemodynamic measures in patients with acute or sub-acute stroke.

Searching

EMBASE, PubMed and the Cochrane Library were searched up to May 2006; the search terms were reported. The reference lists of retrieved articles and non-systematic reviews were checked for additional studies. The search was restricted to studies reported in English.

Study selection

Randomised controlled trials (RCTs) of NO donors in patients with acute or sub-acute stroke, that reported haemodynamic outcomes, were eligible for inclusion. All studies recruited patients with either ischaemic stroke or primary intracerebral haemorrhage, and evaluated glyceryl trinitrate (GTN) administered at doses of 5 to 10 mg. The patients were enrolled between 72.2 and 99.6 hours after their stroke. The mean age of the participants ranged from 69.4 to 73.7 years and 27.8 to 48.6% were male.

The authors did not state how the papers were selected for the review, or how many reviewers performed the selection.

Assessment of study quality

Study quality was assessed in terms of method of randomisation, blinding, reporting of withdrawals, generation of random numbers and allocation concealment, to obtain a quality score of between 0 and 5; a score of 5 reflected the highest quality. The authors did not report whether the individual patient data (IPD), or any inconsistencies, were checked with trial investigators or published summary statistics.

The authors did not state how the validity assessment was performed.

Data extraction

IPD were obtained and haemodynamic measures were extracted: systolic and diastolic blood-pressure (BP), mean arterial pressure, mid BP, pulse pressure, and pulse pressure divided by mean arterial pressure. One study was split to allow categorisation according to the dose of GTN given. The methods used were not reported clearly.

The authors did not state how the data were extracted for the review, or how many reviewers performed the data extraction.

Methods of synthesis

A random-effects model was used to calculate the weighted mean differences (WMDs) and 95% confidence intervals (CIs) for continuous outcomes. The analysis was adjusted for baseline measures.

Statistical heterogeneity was assessed using a χ² test. Differences between the study characteristics were illustrated in a forest plot.

Results of the review

Three RCTs (n=145) were included.

The included trials were of high quality: two scored 4 and one scored 5.

GTN significantly reduced systolic BP (WMD -9.8 mmHg, 95% CI: -12.9, -6.7, p<0.0001), diastolic BP (WMD -4.4 mmHg, 95% CI: -6.4, -2.5, p<0.0001), mean arterial pressure (WMD -6.4 mmHg, 95% CI: -8.5, -4.3, p<0.0001), mid BP (WMD -7.3 mmHg, 95% CI: -9.6, -5.0, p<0.0001) and pulse pressure (WMD -6.1 mmHg, 95% CI: -9.4, -2.8, p=0.0003). GTN also significantly increased the heart rate (WMD 3.9 beats per minute, 95% CI: 1.7, 6.1, p=0.001). There was no effect of GTN on rate pressure product. There was no significant heterogeneity for any analysis (p=0.05 considered significant).

Authors' conclusions

Findings suggest that the NO donor GTN reduces BP and pulse pressure, plus other derivatives, in acute and sub-acute stroke whilst increasing the heart rate.

CRD commentary

The review addressed a clearly stated research question but had a number of shortcomings. The literature search was restricted to publications in English and there was no specific search for unpublished studies, therefore both publication and language bias may have been present. Inclusion criteria were defined but it was unclear whether appropriate measures were taken to control for error and bias during the review process. There was no reporting of the checking or validation of the IPD, either with the summary results or the trialists. It was unclear whether the included studies represented the entire evidence base available or whether relevant studies were identified for which IPD were unavailable. An assessment of the methodological quality of the included studies was conducted. The methods used to synthesise the studies were appropriate and sources of heterogeneity were explored. The included studies were small with wide CIs for some outcomes, therefore the authors' conclusions may be compromised by the lack of evidence. It is questionable whether these findings are generalisable to the entire stroke population.

Implications of the review for practice and research

The authors did not state any implications for practice or further research.

Funding

Not stated.

Bibliographic details

Gray L J, Sprigg N, Rashid P A, Willmot M R, Bath P M. Effect of nitric oxide donors on blood pressure and pulse pressure in acute and subacute stroke. Journal of Stroke and Cerebrovascular Diseases 2006; 15(6): 245-249. [PubMed: 17904083]

Indexing Status

Subject indexing assigned by CRD

MeSH

Blood Pressure /physiology; Blood Pressure Determination /methods; Brain Ischemia /drug therapy; Cardiac Output, Low /diagnosis; Nitric Oxide Donors /therapeutic use; Nitroglycerin /therapeutic use; Protective Agents /therapeutic use; Stroke /drug therapy

AccessionNumber

12006009156

Database entry date

01/12/2008

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.