Topical Glyceryl Trinitrate and Noninsertional Achilles Tendinopathy Topical glyceryl trinitrate treatment of chronic patellar tendinopathy: a randomised, double-blind, placebo-controlled clinical trial Topical glyceryl trinitrate treatment of chronic noninsertional achilles tendinopathy. A randomized, double-blind, placebo-controlled trial. Topical Glyceryl Trinitrate Application in the Treatment of Chronic Supraspinatus Tendinopathy Management of tennis elbow with topical glyceryl trinitrate. Treatment of chronic anal fissure with topical glyceryl trinitrate: a double-blind, placebo-controlled trial. Randomised trial of topical 0.2% glyceryl trinitrate and lateral internal sphincterotomy for the treatment of patients with chronic anal fissure: long-term follow-up. Topical diltiazem hydrochloride and glyceryl trinitrate in the treatment of chronic anal fissure. Lateral internal sphincterotomy is not redundant in the era of glyceryl trinitrate therapy for chronic anal fissure Comparison of topical glyceryl trinitrate with lignocaine ointment for treatment of anal fissure: a randomised controlled trial. The use of glyceryl trinitrate (GTN) in the treatment of chronic anal fissure in children. Topical 0.2% glyceryl trinitrate ointment for anal fissures: long‐term efficacy in routine clinical practice Comparison of Topical Glyceryl Trinitrate Ointment and Oral Nifedipine in the Treatment of Chronic Anal Fissure
Background Topical glyceryl trinitrate ( GTN ) therapy has been advocated in the treatment of Achilles tendinopathy . The mechanism of action is unknown but may be related to modulation of local nitric oxide levels . Hypothesis Topical GTN therapy for noninsertional Achilles tendinopathy will significantly enhance clinical improvement and will be associated with increased collagen synthesis within the tendon . Study Design R and omized controlled clinical trial ; Level of evidence , 1 . Methods Forty patients were recruited . Twenty underwent  st and ard nonoperative physical therapy  , and 20 underwent physical therapy and topical GTN daily . Clinical outcome was assessed using the Ankle Osteoarthritis Scale ( AOS ) visual analog score . Patients who failed to improve with conservative measures and who underwent surgical decompression had histological and immunohistochemical examination of sample s from the Achilles tendon . Results Glyceryl trinitrate did not offer any additional clinical benefit over st and ard nonoperative treatment for noninsertional Achilles tendinopathy . After 6 months of treatment , there was no significant difference in scores between the groups for pain ( 3.0 vs 3.1 , P = .42 ) or disability ( 2.15 vs 2.25 , P = .38 ) . Histological examination did not show any difference in neovascularization , collagen synthesis , or stimulated fibroblasts between the 2 groups . There was no evidence of modulation of nitric oxide synthase , a marker of nitric oxide production , in those tendons treated with GTN . Conclusion and Clinical Relevance This study has failed to support the clinical benefit of GTN patches previously described in the literature . In the available tissue sample s , there did not appear to be any histological or immunohistochemical change in Achilles tendinopathy treated with GTN compared with those undergoing st and ard nonoperative therapy Objectives To assess if continuous topical glyceryl trinitrate ( GTN ) treatment improves outcome in patients with chronic patellar tendinopathy when compared with eccentric training alone . Methods R and omised double-blind , placebo-controlled clinical trial comparing a 12-week programme of using a GTN or placebo patch in combination with eccentric squats on a decline board . Measurements were performed at baseline , 6 , 12 and 24 weeks . Primary outcome measure was the Victorian Institute of Sports Assessment -Patella ( VISA-P ) question naire . Secondary outcome measures were patient satisfaction and pain scores during sports . Generalised estimated equation was used to analyse the treatment , time and treatment × time effect . Analyses were performed following the intention-to-treat principle . Results VISA-P scores for both groups improved over the study period to 75.0±16.2 and 80.7±22.1 at 24 weeks . Results showed a significant effect for time ( p<0.01 ) but no effect for treatment × time ( p=0.80 ) . Mean Visual Analogue Scores pain scores during sports for both groups increased over the study period to 6.6±3 and 7.8±3.1 . Results showed a significant effect for time ( p<0.01 ) but no effect for treatment × time ( p=0.38 ) . Patient satisfaction showed no difference between GTN and placebo groups ( p=0.25 ) after 24 weeks , but did show a significant difference over time ( p=0.01 ) . Three patients in the GTN group reported some rash . Conclusion It seems that continuous topical GTN treatment in addition to an eccentric exercise programme does not improve clinical outcome compared to placebo patches and an eccentric exercise programme in patients with chronic patellar tendinopathy BACKGROUND Noninsertional Achilles tendinopathy is a degenerative overuse disorder . No method has been universally successful in treating this condition . Topically applied nitric oxide has been shown , in animal models , to be effective for the treatment of fractures and cutaneous wounds through mechanisms that may include stimulation of collagen synthesis in fibroblasts . The goal of the present study was to determine if topical glyceryl trinitrate improves clinical outcome measures in patients with Achilles tendinopathy . METHODS A prospect i ve , r and omized , double-blind , placebo-controlled trial involving a total of sixty-five patients ( eighty-four Achilles tendons ) was performed to compare continuous application of topical glyceryl trinitrate ( at a dosage of 1.25 mg per twenty-four hours ) with rehabilitation alone for the treatment of noninsertional Achilles tendinopathy . RESULTS Compared with the control group , the glyceryl trinitrate group showed reduced pain with activity at twelve weeks ( p = 0.02 ) and twenty-four weeks ( p = 0.03 ) , reduced night pain at twelve weeks ( p = 0.04 ) , reduced tenderness at twelve weeks ( p = 0.02 ) , decreased pain scores after the hop test at twenty-four weeks ( p = 0.005 ) , and increased ankle plantar flexor mean total work compared with the baseline level at twenty-four weeks ( p = 0.04 ) . Twenty-eight ( 78 % ) of thirty-six tendons in the glyceryl trinitrate group were asymptomatic with activities of daily living at six months , compared with twenty ( 49 % ) of forty-one tendons in the placebo group ( p = 0.001 , chi-square analysis ) . The mean effect size for all outcome measures was 0.14 . CONCLUSIONS Topical glyceryl trinitrate significantly reduced pain with activity and at night , improved functional measures , and improved outcomes in patients with Achilles tendinopathy Background Topical glyceryl trinitrate therapy has previously demonstrated short-term pain reduction in patients with supraspinatus tendinopathy . Hypothesis Topical glyceryl trinitrate improves outcome measures in patients with supraspinatus tendinopathy . Study Design R and omized controlled clinical trial ; Level of evidence , 1 . Methods Fifty-three patients ( 57 shoulders ) were recruited , and the authors completed a prospect i ve , r and omized , double-blinded , placebo-controlled clinical trial of continuous topical glyceryl trinitrate treatment ( 1.25 mg/24-h glyceryl trinitrate ) . Results The glyceryl trinitrate group had significantly reduced shoulder pain with activity , at night , and at rest at week 24 ( P = . 03 ) ; reduced internal rotation impingement at week 24 ( P = . 02 ) ; increased range of motion in abduction and internal rotation at week 24 ( P = . 04 ) ; and increased force at weeks 12 and 24 with supraspinatus muscle testing ( P = . 001 ) , external rotation ( P = . 04 ) , internal rotation ( P = . 01 ) , adduction ( P = . 04 ) , and subscapularis pushoff ( P = . 01 ) . Forty-six percent of patients on glyceryl trinitrate patches were asymptomatic with activities of daily living at 6 months compared with 24 % of patients with tendon rehabilitation alone ( P = . 007 , χ2 analysis ) . Mean effect size for all outcome measures was 0.26 . Discussion Topical glyceryl trinitrate treatment significantly improved pain scores , range of motion , internal rotation impingement , muscular force , and patient outcomes in patients with supraspinatus tendinopathy . Topical glyceryl trinitrate should be included as part of nonsurgical management of chronic tendinopathies OBJECTIVE The aim of this study was to evaluate the treatment results of the application of nitric oxide ( NO ) in the form of topical glyceryl trinitrate ( GTN ) for the treatment of lateral epicondylitis ( LE ) . METHODS The study included 40 patients with LE r and omized into 2 equal groups . Selection criteria included the presence of pain , tenderness , and positive pain stimulating maneuvers .  Glyceryl trinitrate patches were applied to the area of maximal tenderness once a day in the treatment group and placebo patches in the control group . Outcomes in terms of pain relief was assessed using the visual analog scale ( VAS ) and were evaluated according to the criteria of Verhaar et al. Excellent or good results were considered successful . Differences in VAS scores between the two groups were calculated using the Mann-Whitney U-test and the chi-square test was used to investigate distributions of categorical variables ( sex , affected side ) and good and excellent results among groups . RESULTS There were no significant differences in any of the baseline clinical parameters between groups . At the 3rd week follow-up , there were statistically significant differences in the pain measured using VAS between groups ( mean VAS score of the control and treatment groups were 6.45 and 3.15 , respectively ) ( p=0.001 ) . Patients in the GTN group and control group had lower VAS pain scores and reduced elbow pain at 3 weeks ( 3.15 vs 8.05 in the GTN and 6.45 vs 8.80 in the control group ) . In the control group , no patient had excellent or good results while 18 ( 90 % ) patients in treatment group reported successful treatment . There was statistically significant difference in the VAS measured at 6 months between groups ( mean VAS score of the control and treatment groups were 4.85 and 0.70 , respectively ) ( p=0.001 ) . CONCLUSION The administration of NO directly over an area of tendinopathy through a GTN patch reduces pain and other symptoms in chronic LE BACKGROUND Topical glyceryl trinitrate ( GTN ) may produce healing of anal fissure by decreasing the high resting anal sphincter pressure in these patients . The present study assessed the efficacy of GTN in chronic anal fissure in a double-blind placebo-controlled trial . METHOD Patients with chronic anal fissure ( for more than 8 weeks ) underwent measurement of maximum anal resting pressure ( MARP ) before and 12 minutes after application of either 0.2 % GTN or placebo ointment in a r and omized manner . They then received twice-daily local application of their respective ointment for 6 weeks . Symptoms and healing of fissure were assessed ; patients were evaluated at 3 months for evidence of relapse . RESULTS 19 adult patients ( 12 men ) were studied ; 10 received GTN and 9 placebo .  Mean ( SD ) MARP decreased from 131.0 ( 32.3 ) cm H2O to 93.5 ( 28.4 ) cm H2O ( p<0.05 ) with GTN and from 150.5 ( 36.9 ) cm H2O to 142.8 ( 35.0 ) cm H2O ( p = ns ) with placebo .  Fissure healed in 7 of 10 patients treated with GTN and 2 of 9 patients treated with placebo ( p<0.05 ) . There was no relapse of fissure in either group . CONCLUSION Local application of GTN was effective in healing chronic anal fissure OBJECTIVE To compare outcomes 24 months after treatment of chronic anal fissure with 0.2 % glyceryl trinitrate ointment ( GTN ) or lateral internal sphincterotomy .  DESIGN Prospect i ve , r and omised trial . SETTING One teaching , one private , and 3 district hospitals , U.K. SUBJECTS Seventy patients were r and omised into two groups of 35 each to use  0.2 % GTN ointment or have a lateral internal sphincterotomy .  MAIN OUTCOME MEASURES Resolution of symptoms and healing of fissures assessed after 24 months . RESULTS All those operated on were initially cured but one fissure recurred after 8 months . Nineteen of 35 fissures treated with GTN  healed . The remaining 16 patients r and omised to use GTN ointment whose fissures did not heal were then treated by sphincterotomy . Three patients whose fissures healed successfully with GTN developed recurrences within 6 months of completing treatment . The remaining 16 of 19 patients treated with GTN whose fissures healed were free of symptoms with no clinical evidence of recurrence after 24 months follow-up . CONCLUSIONS Many anal fissures heal with topical treatment with GTN . Lateral internal sphincterotomy remains effective but should be reserved for patients who fail to respond to initial chemical sphincterotomy OBJECTIVE To compare the symptomatic relief , healing and side-effects of topical diltiazem ( DTZ ) and glyceryl trinitrate in the treatment of chronic anal fissure .  STUDY DESIGN R and omized controlled trial . PLACE AND DURATION OF STUDY The Surgical Outpatient Department of Civil Hospital , Karachi , from March 2006 to February 2007 . METHODOLOGY Patients with chronic anal fissure were included in the study and r and omized to two groups . One group was administered topical 2 % diltiazem hydrochloride and other was given 0.2 % glyceryl trinitrate ( GTN ) , perianally twice daily for 8 weeks . Patients with anal fissure due to other diseases like inflammatory bowel disease , malignancy , sexually transmitted diseases , previous treatment with local ointment or surgery ; patients who required anal surgery for any concurrent disease like hemorrhoids , pregnant women and patients with significant cardiovascular conditions were excluded . There were four follow-up sessions during the course of treatment . Healing and side-effects were recorded . Analysis was done by SPSS version 10 on intention-to-treat basis . Chi-square was used where appropriate . RESULTS Eighty patients with symptomatic chronic anal fissure were included in the study and equally divided into two groups . After 8 weeks of treatment healing occurred in 31 of 40 patients treated with diltiazem and 33 of 40 patients treated with GTN ( p = 0.576 ) . There were less side-effects with DTZ ( n=13 ) than with GTN ( n=29 , p < 0.001 ] . In particular , headache occurred more commonly with GTN ( n=27 ) than with DTZ ( n=9 , p < 0.0001 ) . CONCLUSION Diltiazem hydrochloride and glyceryl trinitrate were equally effective in healing chronic anal fissure .  Diltiazem caused fewer side-effects particularly headache than glyceryl trinitrate ointment . Diltiazem may be the first-line treatment for chemical sphincterotomy for the chronic anal fissure Lateral internal sphincterotomy has been the st and ard treatment for chronic anal fissure , but fissure healing rates of up to 80 % with topical glyceryl trinitrate ( GTN ) treatment have suggested that this operation may become redundant . We evaluated the results of topical treatment of chronic anal fissures with 0.2 % GTN for 6 weeks in the outpatient clinical setting , outside the confines of a r and omized clinical trial . The role of lateral internal sphincterotomy in the GTN era was also assessed . GTN induced fissure healing in 21 of 49 consecutive patients .  Fissures healed spontaneously in 2 patients who discontinued GTN because of headache . Lateral internal sphincterotomy was performed in 26 patients who had persistent symptoms after 6 weeks of GTN therapy . At the 6-week post-sphincterotomy review , all fissures had healed and there were no complications . In this study topical GTN for treatment of chronic anal fissure in the outpatient setting was not as effective as demonstrated in controlled clinical trials . Lateral internal sphincterotomy is still a good therapeutic option , especially in patients not responding to GTN INTRODUCTION Topical glyceryl trinitrate ( GTN ) has gained popularity as a treatment for anal fissure in the West . In our country , lignocaine is still the current treatment for the entity . This study was done to compare the effect of GTN with lignocaine in terms of healing rate and recurrence in South Asian population . METHODS A prospect i ve , double blinded , r and omised controlled trial was conducted on 50 patients ( both treatment arms included ) of all ages and either gender with a clinical diagnosis of anal fissure . Group A was given 0.2 % GTN ointment and Group B was given lignocaine ointment . Both subjective and objective signs of healing were assessed and adverse effects of the treatment were sought . RESULTS Symptomatic relief was earlier with GTN as compared with lignocaine .  Pain relief was steady and sustained in those treated with GTN but returned to pre-treatment status within 5 weeks in patients with lignocaine . After 8 weeks of treatment , 80 % of patients in Group A showed clinical signs of healing compared to 32 % in Group B ( p=0.001 ) . Headache was the main side effect of GTN . At 6-month follow-up , recurrence was seen in 3/8 patients in Group B compared to 8/20 in the GTN Group ( p=1 ) . CONCLUSION Topical GTN has earlier and a higher rate of clinical healing of anal fissure with acceptable side effects . The recurrence rate is high and comparable to lignocaine ointment . It is a safe and an effective treatment of anal fissure in a South Asian population BACKGROUND 0.2 per cent topical glyceryl trinitrate ( GTN ) ointment heals up to two-thirds of  chronic anal fissures in adults although many patients experience troublesome headaches . This double blind r and omised pilot study assessed the efficacy and side effects of 0.1 and 0.05 per cent GTN ointment in treatment of chronic anal fissures in children . MATERIAL / METHODS 15 consecutive children with chronic anal fissures were r and omised to receive either 0.05 or 0.1 per cent GTN ointment applied topically twice daily for eight weeks . Clinical review was undertaken at weeks 4 and 8 and questions relating to symptoms and the incidence of headache were asked . RESULTS The median age of the 15 ( 8 male ) patients was 6 years ( range 3 - 13 ) . There were 5 anterior and 10 posterior fissures . The median duration of symptoms was 9 ( 3 - 30 ) months . 13/15 ( 86.7 % ) patients were taking laxatives at the time of referral . Fissure healing was complete at 8 weeks in all seven patients who received 0.05 % and in 5/8 ( 62.5 % ) patients using the 0.1 % ointment ( Fisher 's exact test , not significant ) . One patient from each arm experienced headaches during the first week of the trial which resolved without treatment and did not affect compliance . There were no other side effects . CONCLUSIONS Topical glyceryl trinitrate ointment is effective in healing chronic anal fissures in children .  Healing rates and side effect profile are comparable when either 0.05 or 0.1 per cent ointment is used Objective R and omized controlled trials have reported fissure healing rates of 60–70 % using topical 0.2 % GTN ointment , but the effectiveness of this therapy in routine clinical practice , particularly in the long term , is uncertain . This study aim ed to evaluate the efficacy of  topical GTN  for anal fissures in an outpatient setting Abstract This study was design ed to compare the effect of topical glyceryl trinitrate ( GTN ) and oral nifedipine treatments on maximal anal resting pressure ( MarP ) and subsequently to assess their effectiveness in healing of chronic anal fissure ( CAF ) . Patients were allocated r and omly to receive either oral nifedipine retard ( 10 patients ) 20 mg twice daily or instructed to apply glyceryl trinitrate ( 0.2 percent ) ointment ( 10 patients ) into the lower half of the anal canal twice daily . They were review ed and assessed at the first visit and every fortnight for measurement of MARP , pain scores , blood pressure , pulse rate , healing of the fissure and adverse effects . Treatment were continued until healing had occurred or for up to 8 weeks . MARP values before and after application of the GTN ointment was 113.2 cm H2O and 72.5 cm H2O respectively ( P < 0.001 ) . Nifedipine caused a reduction in mean MARP from 105.2 to 74.0 cm H2O ( P < 0.001 ) . Linear analogue pain scores were significantly reduced after 2 weeks treatment with GTN and nifedipine ( P < 0.001 ) and continued throughout the treatment period . At the end of the study ; 7 of the 10 patients in the GTN group were deemed to be healed ( 5 ) or improved ( 2 ) , compared with 6 of the 10 patients in the nifedipine group ( 5 healed , 1 improved ) . Headaches occurred in 3 patients in the GTN group , compared with one patient in the nifedipine group . There was no significant difference between GTN and nifedipine in terms of reduction in MARP and pain score , healing of the fissure and incidence of early recurrence and side effects of treatments . We conclude that GTN ointment and oral nifedipine are equally effective in the treatment of chronic anal fissure
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
Objective To produce a best evidence synthesis of the clinical effects of topical glyceryl trinitrate ( GTN ) in the treatment of tendinopathies .