Commentary

Nitroglycerin for Tendinopathy


 

The Problem

Jon O. Ebbert (left) and Eric G. Tangalos

A 32-year-old male with a history of carpel tunnel syndrome and cannabis dependence presents with a several-month history of aching right elbow pain. He works as a customer service representative for a cellular telephone company. The elbow pain is worse when opening jars, using his computer mouse, brushing his teeth, and eating with a utensil. He has been trying the tennis elbow strap recommended to him by a pharmacist with minimal relief. He takes ibuprofen as needed for pain. On examination, he has pain over the lateral epicondyle and pain with resisted pronation. You diagnose him with lateral epicondylitis.

The Question

In patients with lateral epicondylitis, what conservative therapies are more effective than placebo for improving pain and decreasing dysfunction?

The Search

You open PubMed, and use the PubMed "Clinical Queries" search. You enter "tendinopathy" and identify a meta-analysis on topical nitroglycerin.

Our Critique

The search strategy used to retrieve articles seemed exhaustive, data were extracted independently, and quality assessments were conducted. We found the use of nitroglycerin to be an exciting and somewhat novel therapy for tendinopathies. Nitroglycerin is believed to decrease pain, increase function, and promote healing through the promotion of fibroblastic synthesis of collagen. This therapy could be offered as a next line of conservative options for patients who fail to improve with the tennis elbow strap, NSAIDs, and simple rehabilitation exercises.

Clinical Decision

The evidence would suggest that nitroglycerin is likely to benefit this patient with chronic tendinopathy (of at least 6 weeks duration). You discuss the option with the patient and write for nitroglycerin 0.3% in plastibase and have him apply that once per day. He reports 50% improvement with the nitroglycerin but reports intermittent headache that is relieved through the smoked consumption of marijuana.

The Evidence

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," (Arch. Phys. Med. Rehabil. 2010;91:1291-305).

Criteria for study selection: Studies were eligible for inclusion if they were randomized, controlled clinical trials (RCTs) comparing topical nitroglycerin with placebo, a controlled comparison intervention, or standard care. Nitroglycerin formulations could be patches or ointments. Trials were further restricted to those including adults, using pain as an outcome measure, and subjects had a diagnosis of tendinopathy meeting criteria for acute (less than 2 weeks), subacute (2-6 weeks), and chronic (longer than 6 weeks). Searches involving multiple databases were conducted to identify articles published from January 1990 to March 2009.

Outcomes: The primary outcome of interest was pain reduction measured subjectively with visual analog scales or Likert scales or objectively with local tenderness scales. Secondary outcomes included range of motion and strength.

Findings: Searches retrieved 163 published articles, of which 7 were considered potentially relevant. The remaining articles were rejected because they were not RCTs. All seven included studies were deemed to be of high methodologic quality. Five studies evaluated chronic cases, one enrolled subacute and acute cases, and one study included only acute cases. Three studies evaluated patients with shoulder tendinopathies (chronic supraspinatus tendinopathy, acute/subacute rotator cuff tendinitis, acute supraspinatus tendinitis), two selected subjects with elbow tendinopathies (chronic lateral epicondylitis, chronic extensor tendinosis), and two studies evaluated patients with chronic noninsertional Achilles’ tendinopathy. The seven trials involved a total of 446 patients with ages ranging from 18 to 79 years. Five studies compared glyceryl trinitrate with placebo, one study compared nitroglycerin with local injection of a steroid-anesthetic solution, and one study evaluated topical nitroglycerin and tendon rehabilitation, compared with tendon rehabilitation alone. Three studies administered 1.25 mg/24 hours (or one-fourth of a 5 mg/24h patch) daily, one delivered 2.5 mg/24 hours combined with tendon rehabilitation for 24 weeks, one applied 5 mg/24 hours preparations daily for 3 days only, one applied 5 mg/24 hours daily for 3 days up to three trials of 15-day intervals, and one applied three different daily doses: (0.72 mg, 1.44 mg, and 3.6 mg) for 8 weeks. In the meta-analyses, nitroglycerin reduced pain during activities of daily living in chronic tendinopathies [odds ratio 4.44; 95% confidence interval: 2.34-8.40] and in both acute and chronic phases combined (OR 4.86; 95% CI: 2.62-9.02). Two studies reported enhanced joint mobility with topical nitroglycerin and one study (chronic supraspinatus tendinopathy) noted an increase in range of motion, increased shoulder abduction, and internal rotation. With respect to local tenderness, one study reported a reduction in local tenderness at 6 weeks and another observed a reduction at 12 weeks. Three studies reported a significant improvement in peak muscle force as assessed by a dynamometer at 24 weeks. Nitroglycerin is likely to cause headache (OR 1.73; 95% CI: 1.01-2.97), but does not appear to increase the risk for contact dermatitis.

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