Topical glyceryl trinitrate treatment of chronic patellar tendinopathy: a randomised, double-blind, placebo-controlled clinical trial.
Steunebrink M, Zwerver J, Brandsema R, Groenenboom P, Akker-Scheek IV, Weir A. Br J Sports Med. 2012 Aug 28. [Epub ahead of print].
Chronic patellar tendinopathy is a common condition seen in elite and recreational athletes, especially those that participate in sports that involve repetitive jumping and landing. The prevalence has been shown to be 2.5-14% in non-elite athletes and as high as 40-50% in elite basketball and volleyball athletes. Eccentric training has become the standard treatment for chronic tendinopathies, but other treatments are being investigated that try to stimulate tendon regeneration and modulation of tendon pain. Some studies, but not all, have supported the use of continuous topical glyceryl trinitrate (GTN) via patches in chronic tendinopathies including lateral epicondylosis, non-insertional Achilles tendinopathy, and supraspinatus tendinopathy. The objective of the study was to assess if continuous topical GTN treatment improved outcomes among patients with chronic patellar tendinopathy compared to placebo, while both groups underwent heavy-load eccentric training. This study was a randomized, double-blinded, placebo-controlled trial comparing a 12 week program of using a 5mg/24 hour GTN or placebo patch in combination with eccentric squats on a decline board. Thirty-three patients with clinically-diagnosed chronic patellar tendinopathy of at least 3 months were included in the study, with ages ranging from 18-40 years old. The primary outcome was measured with the Victorian Institute of Sports Assessment-Patella (VISA-P) questionnaire at baseline and after 6, 12, and 24 weeks. This questionnaire quantifies pain and activity level, with scores ranging from 0 (no activity/maximum pain) to 100 (maximum activity/no pain). The authors found that both groups of patients improved over the study period, but there was no significant difference found between the two treatment groups. Also, there was no difference found between the groups for the authors’ secondary outcome measures: patient satisfaction rate, and visual analog scale pain scores.
As previous studies have looked at other types of tendinopathies, this was the first study to evaluate the effectiveness of GTN in chronic patellar tendinopathy. The current evidence is conflicting on whether or not GTN patches are clinically effective for tendinopathies. More supporting evidence for the use of GTN in tendinopathy would be helpful because currently it is an off-label use of the medication. Nitric oxide has exhibited a role in fibroblast proliferation, collagen synthesis, contraction of collagen lattices, and macrophage angiogenic activity – all important processes in tendon regeneration. Unfortunately, this study does not support the use of the nitrate patches or offer any improvements in clinical outcomes. Previous studies have reported that about 5-8% of their patients had to stop treatment due to headaches and 5% due to rash. The headaches are caused by the vasodilation effect of nitric oxide on the arteries and veins. A positive finding in this study was that only 3 of the 16 patients receiving GTN patches had a minor rash and they still continued treatment. This finding leads to the author’s question of whether the nitric oxide concentrations reached a sufficient level to stimulate tendon regeneration and may have been a factor for why there was no significant differences in treatment effects. If the nitric oxide levels were too low to produce side effects, it may have been too low to reach the injury site for tendon healing. Even though this study did not produce the desired outcomes, the results reinforce that eccentric training needs to be the core of any treatment regimen and more studies are needed to assess what other treatment options are worth the risk of side effects and cost. What is your clinical experience with nitrate patches and chronic tendinopathy?
Written by: Kris Fayock, MD
Reviewed by: Stephen Thomas
Steunebrink M, Zwerver J, Brandsema R, Groenenboom P, Akker-Scheek IV, & Weir A (2012). Topical glyceryl trinitrate treatment of chronic patellar tendinopathy: a randomised, double-blind, placebo-controlled clinical trial. British Journal of Sports Medicine PMID: 22930695