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A garbage-in-garbage-out review of topical nitroglycerin for tendinopathy

updated

Tags: treatment, tendinosis, medications, pain problems, overuse injury, injury, self-treatment

One article on PainSci cites Challoumas 2019: Achilles Tendinitis Treatment Science

PainSci summary of Challoumas 2019: ?This page is one of thousands in the PainScience.com bibliography. It is not a general article: it is focused on a single scientific paper, and it may provide only just enough context for the summary to make sense. Links to other papers and more general information are provided at the bottom of the page, as often as possible.

This is a lovingly crafted systematic review… of ten rather weak trials of topical glyceryl trinitrate for tendinopathy. Yes, that’s “nitroglycerin,” the stuff that’s explosive undiluted, but also a medicine for heart failure, high blood pressure, anal fissures, and painful periods. And … tendinitis?

I think the most important line in the paper is: “due to the small number of eligible studies, our results on most outcomes had a poor level of evidence.”

So, garbage in, garbage out, which seems to be all we ever get in musculoskeletal medicine. This data can’t answer anything. I wish researchers would stop analyzing clinical trial data that isn’t fit to line a birdcage. When you essentially have no high quality data to review, why bother? All they accomplish is the amplification of ambiguity.

Even if the results could be taken at face value (which they clearly can’t), the good news is modest and mostly derived from secondary outcomes like the rather squishy “satisfaction” and the indirect “strength.” When it comes to the only thing most patients care about, pain, the outcomes were thoroughly mediocre and mixed.

If this stuff really worked, you’d have most trials reporting clearly clinically significant benefits. Instead, what we have here is a mixed bag, ranging from somewhat negative results, a few barely there results, and just a couple positives that start nudging into clinical significance. Those outliers pull up the average just enough for the reviewers to publish a positive conclusion.

But man, it’s just not an impressive batch of numbers. It’s like if you asked 10 kids how much they like an ice cream flavour, and you got two saying “pretty good but I’d rather have chocolate,” three pulling a bit of a yuck-face, and the rest mostly shrugging. Would you recommend that flavour to your favourite 8-year-old? Not with any confidence. And that’s how I feel about recommending GTN based on data like this.

These are classic “promising” results, extremely likely be undermined by the results of higher quality trials. Plus… headaches! This stuff gives some people headaches. It’s not a terrible side effect, but it seems to be much more reliable than the benefit. Some subjects pulled out of these trials because of the headaches.

~ Paul Ingraham

original abstract Abstracts here may not perfectly match originals, for a variety of technical and practical reasons. Some abstacts are truncated for my purposes here, if they are particularly long-winded and unhelpful. I occasionally add clarifying notes. And I make some minor corrections.

OBJECTIVE: To produce a best evidence synthesis of the clinical effects of topical glyceryl trinitrate (GTN) in the treatment of tendinopathies.

DESIGN: A systematic review of published randomised controlled trials (RCTs) of the use of GTN in patients with tendinopathy.

DATA SOURCES: MEDLINE, Embase, Scopus and CINAHL from database inception to January 2018.

METHODS: We examined RCTs comparing the effects of topical GTN with either placebo or other treatments on tendinopathy. Overall quality of each eligible study was determined based on a combined assessment of internal validity, external validity and precision. The level of evidence for each assessed parameter was rated based on the system by van Tulder et al.

RESULTS: A total of 10 eligible RCTs were identified including patients with tendinopathy of the rotator cuff (n=4), wrist extensors (n=3), Achilles (n=2) and patellar (n=1) tendons. For all tendinopathies, improvements in pain were significant when comparing GTN versus placebo in the short term (<8 weeks; poor evidence). Significant improvements in midterm outcomes for treatment with GTN versus placebo included the following: patient satisfaction (strong evidence); chances of being asymptomatic with activities of daily living (strong evidence); range of movement (moderate evidence); strength (moderate evidence); pain (at night and with activity; poor evidence) and local tenderness (poor evidence). Patients treated with topical GTN reported a higher incidence of headaches than those who received placebo (moderate evidence).

CONCLUSIONS AND RELEVANCE: Treatment of tendinopathies with topical GTN for up to 6 months appears to be superior to placebo and may therefore be a useful adjunct to the treating healthcare professions.

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