Is nitroglycerin (glyceryl trinitrate) effective for treating tendinopathy?

Nitroglycerin for Tendinopathy

Topical nitroglycerin (glyceryl trinitrate) is an effective adjunctive treatment for chronic tendinopathies, particularly for reducing pain during activities of daily living and increasing tendon strength, though it should not be considered first-line therapy.

Evidence Quality and Recommendations

The 2005 American Family Physician guidelines on tendinopathy do not specifically mention nitroglycerin among their recommended treatments, focusing instead on relative rest, eccentric strengthening, NSAIDs, and corticosteroid injections 1. However, subsequent research has established a role for topical nitroglycerin as an adjunctive therapy.

Efficacy for Chronic Tendinopathies

Pain Reduction

• Strong evidence (Level 1) demonstrates that topical nitroglycerin significantly reduces pain during activities of daily living in chronic tendinopathies (odds ratio 4.44,95% CI 2.34-8.40) 2, 3.
• Pain reduction becomes significant at 12 weeks of treatment and is maintained through 24 weeks 4, 5.
• For Achilles tendinopathy specifically, patients using glyceryl trinitrate reported less pain with activity (mean score 0.4 vs 1.0, P=0.03) and on functional testing at 24 weeks 4.

Functional Improvements

• Strong evidence shows increased patient satisfaction and higher rates of becoming asymptomatic with activities of daily living (46% vs 24% asymptomatic at 6 months for rotator cuff tendinopathy) 6, 5.
• Moderate evidence supports improvements in range of motion and muscle strength after 24 weeks of treatment 6, 5.
• Supraspinatus tendinopathy patients demonstrated increased force with muscle testing at 12 and 24 weeks (P=0.001) 5.

Efficacy for Acute Tendinopathies

• Evidence for acute tendinopathies (<2 weeks duration) is limited and conflicting (Level 3) 2, 3.
• When comparing nitroglycerin to corticosteroid infiltration in acute settings, corticosteroid injection appears superior 3.

Treatment Protocol

Dosing

• Apply 1.25 mg of glyceryl trinitrate per 24 hours via transdermal patch (typically 1/4 of a standard 5mg patch) 4, 5.
• Apply daily to the site of maximal tenderness for a minimum of 12-24 weeks 4, 5.

Combination Therapy

• Nitroglycerin should be used as an adjunct to standard tendinopathy rehabilitation, including eccentric strengthening exercises, relative rest, and activity modification 1, 4, 5.
• The combination of nitroglycerin with tendon rehabilitation is more effective than rehabilitation alone 5.

Adverse Effects

Common Side Effects

• Headache is the most common adverse effect, occurring significantly more frequently than placebo (odds ratio 1.73,95% CI 1.01-2.97) 2, 3.
• Headache rates range from 45-53% of patients, leading to discontinuation in some cases 4.
• Contact dermatitis occurs in approximately 12-16% of patients, with no significant difference from placebo 2, 3.

Management

• Paracetamol (acetaminophen) 500mg can be used to manage nitroglycerin-induced headaches 4.
• Headaches typically improve with continued use as tolerance develops 7.

Clinical Context and Positioning

When to Consider Nitroglycerin

• For chronic tendinopathies (>6 weeks duration) that have not responded adequately to first-line conservative treatments 1, 2.
• As an adjunct to eccentric strengthening programs, which remain the cornerstone of tendinopathy treatment 1.
• When patients can commit to 12-24 weeks of continuous daily application 4, 5.

When NOT to Use

• As first-line monotherapy—standard conservative treatments (relative rest, eccentric strengthening, NSAIDs) should be initiated first 1.
• In acute tendinopathies where evidence is insufficient and corticosteroid injection may be more appropriate 3.
• In patients with contraindications to nitrates, including hypotension (SBP <90 mmHg), severe bradycardia (<50 bpm), or concurrent phosphodiesterase inhibitor use 1, 7.

Important Caveats

• The mechanism of benefit remains unclear, though theories include improved collagen synthesis and increased blood flow to hypovascular tendon regions 1, 2.
• Benefits typically require 12 weeks of continuous use before becoming clinically apparent 4, 5.
• Surgery remains the definitive option for patients who fail 3-6 months of comprehensive conservative therapy, including nitroglycerin 1.
• The evidence base consists primarily of studies on Achilles, rotator cuff, and lateral epicondyle tendinopathies; extrapolation to other tendons should be done cautiously 6.