Review article (meta-analysis)
Evidence on the Effectiveness of Topical Nitroglycerin in the Treatment of Tendinopathies: A Systematic Review and Meta-Analysis

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Abstract

Gambito ED, Gonzalez-Suarez CB, Oquiñena TI, Agbayani RB. Evidence on the effectiveness of topical nitroglycerin in the treatment of tendinopathies: a systematic review and meta-analysis.

Objective

To evaluate evidence on the effectiveness of topical nitroglycerin (NTG) in treating tendinopathies.

Data Sources

Systematic searches were conducted on ScienceDirect, Scirus, Highwire Press Stanford University, PubMed Central, Directory of Open Access Journals, Free Medical Journals, Free Full Text, Bioline International, Findarticles, BioMed Central, IndMed, OpenMD, QMed, Geneva Foundation for Medical Education and Research, Scientific Electronic Library Online, eMedicine/Medscape/Medline, Biomedical E-journals, Current Contents Connect, Journal of Medical Internet Research, Cochrane, Turning Research Into Practice, Ovid, and EBSCO databases. There were no restrictions regarding the language of publication.

Study Selection

All clinical controlled trials or randomized controlled trials (RCTs) evaluating the effects of NTG for patients with acute, subacute, or chronic tendinopathies, whether the said intervention was placebo-controlled or controlled against a comparator intervention, were considered for inclusion.

Data Extraction

A reviewer extracted data from included studies using a data extraction form by the Joanna Briggs Institute.

Data Synthesis

Methodologic quality of studies was assessed by 2 independent reviewers through a critical appraisal form by the Alberta Heritage Foundation. Qualitative analyses of data were done using a rating system devised by Van Tulder and colleagues. Where possible, meta-analyses of data were performed. Seven clinically relevant and high-quality RCTs involving 446 subjects were identified and included in this review. Meta-analysis showed that NTG has a positive effect in pain reduction during activities of daily living in chronic tendinopathies, with an odds ratio of 4.44 (95% confidence interval [CI], 2.34–8.40), and in both acute and chronic phases combined, with an odds ratio of 4.86 (95% CI, 2.62–9.02). There is also qualitative, strong (Level 1) evidence that NTG is effective in enhancing tendon forces in the chronic phase. There is limited and/or conflicting evidence (Level 3) for other outcomes in the chronic phase and all outcomes in the acute phase. There is a significant between-group difference between NTG and control in the incidence of headache, with an odds ratio of 1.73 (95% CI, 1.01–2.97). No significant difference was observed in the occurrence of contact dermatitis, with an odds ratio of 2.12 (95% CI, .89–5.02).

Conclusions

In chronic tendinopathies, there is strong evidence for NTG in relieving pain during activities of daily living, and increasing tendon strength. Further studies are needed to explore the role of this promising intervention in all phases of tendinopathies.

Section snippets

Criteria for Considering Studies for This Review

Studies were considered eligible for inclusion in this review if they were clinical control trials or RCTs comparing topical nitroglycerin intervention with a placebo intervention, a controlled comparison intervention, or standard care (defined as a treatment option that is normally given).

Participants

Inclusion in this review was restricted to trials with participants meeting the following criteria: (1) adult subjects (>18y of age); (2) any nationality or race; (3) presence of pain as an outcome measure;

Study Inclusion

The search of the literature yielded a total of 163 published articles. No unpublished manuscripts were identified. Of the 163 published articles, 7 were considered potentially relevant, derived from the following databases: PubMed,8, 10, 11, 12, 14 Turning Research Into Practice,9 and ScienceDirect.13 The remaining 156 articles were outrightly rejected because they were non-RCTs (1 review article, 70 descriptive studies, 48 case reports, 25 case series, 1 retrospective study, 11 prospective

Discussion

Individually, all 5 placebo-controlled studies8, 9, 10, 11, 13 reported analgesic effects of topical nitroglycerin beyond a placebo response. One study,14 however, reported no significant difference on pain reduction compared with the control group. At present, there is still limited evidence to support the role of topical nitroglycerin in improving outcomes for acute and subacute tendinopathies. This is primarily due to the inadequacy of relevant RCTs. In the acute phase, only 1 study

Conclusions

The results of this review provide fairly strong evidence for the effectiveness of nitroglycerin in pain reduction in activities of daily living for chronic tendinopathies as compared with placebo. There are many promising advantages of using topical glyceryl nitrates in tendinopathies. These include increased compliance, because it is easily applied and is relatively more economical than other treatment alternatives. Furthermore, it may potentially reduce the risk of more invasive management

References (20)

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