Objectives
To summarize and compare evidence on harms in sildenafil- and placebo-treated men
with erectile dysfunction (ED) in a systematic review and meta-analysis.
Methods
Randomized placebo-controlled trials (RCTs) were identified using an electronic search
in MEDLINE, EMBASE, PsycINFO, SCOPUS, and Cochrane CENTRAL. The rates of any adverse
events (AEs), most commonly reported AEs, withdrawals because of adverse events, and
serious adverse events were ascertained and compared between sildenafil and placebo
groups. The results of men with ED were stratified by clinical condition(s). Statistical
heterogeneity was explored. Meta-analyses based on random-effects model were also
performed.
Results
A total of 49 RCTs were included. Sildenafil-treated men had a higher risk for all-cause
AEs (RR = 1.56, 95% CI: 1.38, 1.76), headache, flushing, dyspepsia, and visual disturbances
compared with placebo-treated men. The magnitude of excess risk was greater in fixed-
than in flexible-dose trials. The rates of serious adverse events and withdrawals
because of adverse events did not differ in sildenafil vs placebo groups. A higher
dose of sildenafil corresponded to a greater risk of AEs. The increased risk of harms
was observed within and across clinically defined specific groups of patients.
Conclusions
There was a lack of RCTs reporting long-term (>6 months) harms data. In short-term
trials, men with ED randomized to sildenafil had an increased risk of all-cause any
AEs, headache, flushing, dyspepsia, and visual disturbances. The exploration of different
modes of dose optimization of sildenafil may be warranted.
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References
- NIH Consensus Development Panel on Impotence.JAMA. 1993; 270: 83-90
- Impotence and its medical and psychosocial correlates: results of the Massachusetts male aging study.J Urol. 1994; 151: 54-61
- Incidence of erectile dysfunction in men 40-69 years old: longitudinal results from the Massachusetts male aging study.J Urol. 2000; 163: 460-463
- Erectile dysfunction: management update.Can Med Assoc J. 2004; 170: 1429-1437
- Sildenafil: an orally active type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction.Int J Impot Res. 1996; 8: 47-52
- Clinical safety of oral sildenafil citrate (Viagra) in the treatment of erectile dysfunction.Int J Impot Res. 1998; 10: 69-73
- PDE5 inhibitors and permanent visual loss.Int J Impot Res. 2005; 17: 547-549
Tsertsvadze A, Yazdi F, Fink HA, et al. Diagnosis and treatment of erectile dysfunction. AHRQ Evidence Report/Technology Assessment 171. Available at: http://www.ahrq.gov/downloads/pub/evidence/pdf/erectiledys/erecdys.pdf on 26-5-2009. Accessed May 26, 2009.
- Assessing the quality of reports of randomized clinical trials: is blinding necessary?.Control Clin Trials. 1996; 17: 1-12
- Allocation concealment in randomised trials: defending against deciphering.Lancet. 2002; 359: 614-618
- Measuring inconsistency in meta-analyses.BMJ. 2003; 327: 557-560
- Meta-analysis in clinical trials.Control Clin Trials. 1986; 7: 177-188
- Treatment of erectile dysfunction in men with depressive symptoms: results of a placebo-controlled trial with sildenafil citrate.Am J Psychiatry. 2001; 158: 1623-1630
- The efficacy and safety of oral sildenafil in Thai men with erectile dysfunction: a randomized, double-blind, placebo controlled, flexible-dose study.J Med Assoc Thai. 2003; 86: 195-205
- Sildenafil citrate for treatment of erectile dysfunction in men with type 1 diabetes: results of a randomized controlled trial.Diab Care. 2003; 26: 279-284
- A double-blind, randomised-placebo, controlled, parallel group, multicenter, flexible-dose escalation study to assess the efficacy and safety of sildenafil administered as required to male outpatients with erectile dysfunction in Korea.Int J Impot Res. 2003; 15: 80-86
- Efficacy and safety of sildenafil citrate (Viagra) for the treatment of erectile dysfunction in men in Egypt and South Africa.Int J Impot Res. 2003; 15: 25-29
- Efficacy and safety of sildenafil citrate in men with erectile dysfunction and stable coronary artery disease.Am J Cardiol. 2004; 93: 147-153
- Sildenafil, a novel effective oral therapy for male erectile dysfunction.Br J Urol. 1996; 78: 257-261
- for Sildenafil Study Group.N Engl J Med. 1998; 338: 1397-1404
- for The assess-1 Study Group.Urology. 2000; 56: 635-640
- A dose-escalation study to assess the efficacy and safety of sildenafil citrate in men with erectile dysfunction.BJU Int. 2001; 87: 75-81
- Efficacy and safety of sildenafil citrate in the treatment of men with mild to moderate erectile dysfunction.Br J Psychiatry. 2001; 178: 325-330
- Efficacy and safety of sildenafil citrate (Viagra) in black and Hispanic American men.Urology. 2002; 60: 39-48
- Treatment of antidepressant-associated sexual dysfunction with sildenafil: a randomized controlled trial.JAMA. 2003; 289: 56-64
- Sildenafil: study of a novel oral treatment for erectile dysfunction in diabetic men.Diabet Med. 1998; 15: 821-825
- for Sildenafil Diabetes Study Group.JAMA. 1999; 281: 421-426
- Long-term efficacy and safety of oral Viagra (sildenafil citrate) in men with erectile dysfunction and the effect of randomised treatment withdrawal.Int J Impot Res. 2000; 12: 177-182
- Sildenafil citrate (Viagra) is effective and well tolerated for treating erectile dysfunction of psychogenic or mixed aetiology.Int J Clin Pract. 2000; 54: 561-566
- Assess-3: a randomised, double-blind, flexible-dose clinical trial of the efficacy and safety of oral sildenafil in the treatment of men with erectile dysfunction in Taiwan.Int J Impot Res. 2001; 13: 221-229
- Sildenafil citrate for the treatment of erectile dysfunction in men with type II diabetes mellitus.Diabetologia. 2001; 44: 1296-1301
- Oral sildenafil in the treatment of erectile dysfunction in diabetic men: a randomized double-blind and placebo-controlled study.J Diab Complications. 2004; 18: 205-210
- Use of sildenafil for safe improvement of erectile function and quality of life in men with New York Heart Association classes II and III congestive heart failure: a prospective, placebo-controlled, double-blind crossover trial.Arch Intern Med. 2004; 164: 514-520
- Acetyl-L-carnitine plus propionyl-L-carnitine improve efficacy of sildenafil in treatment of erectile dysfunction after bilateral nerve-sparing radical retropubic prostatectomy.Urology. 2005; 66: 1080-1085
- Efficacy and safety of sildenafil citrate in men with erectile dysfunction and chronic heart failure.Am J Cardiol. 2005; 95: 36-42
- Sildenafil citrate significantly improves nocturnal penile erections in sildenafil non-responding patients with psychogenic erectile dysfunction.Int J Impot Res. 2004; 16: 552-556
- Sublingual sildenafil in the treatment of erectile dysfunction: faster onset of action with less dose.Int J Urol. 2004; 11: 989-992
- Efficacy of sildenafil citrate (Viagra) for the treatment of erectile dysfunction in men in remission from depression.Int Clin Psychopharmacol. 2004; 19: 191-199
- Minimal time to successful intercourse after sildenafil citrate: results of a randomized, double-blind, placebo-controlled trial.Urology. 2003; 62: 400-403
- Efficacy and safety of oral sildenafil citrate (Viagra) in the treatment of male erectile dysfunction in Colombia, Ecuador, and Venezuela: a double-blind, multicenter, placebo-controlled study.Int J Impot Res. 2002; 14: 42-47
- Sildenafil citrate (Viagra) in the treatment of men with erectile dysfunction in southern Latin America: a double-blind, randomized, placebo-controlled, parallel-group, multicenter, flexible-dose escalation study.Int J Impot Res. 2002; 14: 33-41
- Sildenafil citrate (Viagra) and erectile dysfunction following external beam radiotherapy for prostate cancer: a randomized, double-blind, placebo-controlled, cross-over study.Int J Radiat Oncol Biol Phys. 2001; 51: 1190-1195
- Evaluation of oral RO 70–US$0004/003, an alpha1A-adrenoceptor antagonist, in the treatment of male erectile dysfunction.Int J Impot Res. 2001; 13: 157-161
- Efficacy and safety of sildenafil citrate for the treatment of erectile dysfunction in men with cardiovascular disease.Int J Clin Pract. 2001; 55: 171-176
- Sildenafil taken at bedtime significantly increases nocturnal erections: results of a placebo-controlled study.Urology. 2000; 56: 906-911
- Relationship between patient self-assessment of erectile function and the erectile function domain of the international index of erectile function.Urology. 2000; 56: 477-481
- Efficacy and safety of fixed-dose oral sildenafil in the treatment of erectile dysfunction of various etiologies.Urology. 1999; 53: 1011-1018
- Sildenafil citrate (Viagra) in erectile dysfunction: near normalization in men with broad-spectrum erectile dysfunction compared with age-matched healthy control subjects [Erratum appears in Urology. 1999;53:1072].Urology. 1999; 53: 800-805
- Efficacy and safety of oral sildenafil in the treatment of erectile dysfunction: A double-blind, placebo-controlled study of 329 patients.Int J Clin Pract. 1998; 52: 375-379
- Efficacy, safety and tolerability of sildenafil in Brazilian hypertensive patients on multiple antihypertensive drugs.Int Braz J Urol. 2005; 31: 342-355
- Duration of action of sildenafil citrate in men with erectile dysfunction.J Sex Med. 2004; 1: 179-184
- Sildenafil citrate for erectile dysfunction in men receiving multiple antihypertensive agents: a randomized controlled trial.Am J Hypertens. 2004; 17: 1135-1142
- Efficacy and safety of sildenafil citrate for the treatment of erectile dysfunction in Latin America.Braz J Urol. 2001; 27: 148-154
- Sexual function and satisfaction in heterosexual couples when men are administered sildenafil citrate (Viagra) for erectile dysfunction: a multicenter, randomised, double-blind, placebo-controlled trial.Br J Obstet Gynaecol. 2007; 114: 437-447
- Sildenafil citrate improves erectile function and urinary symptoms in men with erectile dysfunction and lower urinary tract symptoms associated with benign prostatic hyperplasia: A randomized, double-blind trial.J Urol. 2007; 177: 1071-1077
- Effectiveness of sildenafil in treating erectile dysfunction in PTSD patients: a double-blind, placebo-controlled crossover study.J Clin Psychopharmacol. 2006; 26: 426-430
- Sildenafil citrate improves self-esteem, confidence, and relationships in men with erectile dysfunction: results from an international, multi-center, double-blind, placebo-controlled trial.J Sex Med. 2006; 3: 521-529
- Efficacy and safety of sildenafil in men with serotonergic antidepressant-associated erectile dysfunction: results from a randomized, double-blind, placebo-controlled trial.J Clin Psychiatry. 2006; 67: 240-246
- Self-esteem, confidence and relationship satisfaction of men with erectile dysfunction treated with sildenafil citrate: a multicenter, randomized, parallel group, double-blind, placebo controlled study in the United States.J Urol. 2006; 175: 1058-1062
- Fundamentals of Clinical Trials.Springer, New York1998
- AUA guideline on the pharmacologic management of premature ejaculation.J Urol. 2004; 172: 290-294
- Erectile dysfunction.J Urol. 2007; 177: 1675-1681
- Sildenafil for male erectile dysfunction: a systematic review and meta-analysis.Arch Intern Med. 2002; 162: 1349-1360
- Sildenafil (Viagra) for male erectile dysfunction: a meta-analysis of clinical trial reports.BMC Urol. 2002; 2: 6
- The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomized trials.Ann Intern Med. 2001; 134: 657-662
- Recovery of erectile function after nerve-sparing radical prostatectomy: improvement with nightly low-dose sildenafil.BJU Int. 2008; 101: 1279-1283
- Long-term treatment of erectile dysfunction with a phosphodiesterase-5 inhibitor and dose optimization based on nocturnal penile tumescence.BJU Int. 2008; 101: 1129-1134
Article info
Publication history
Published online: July 09, 2009
Accepted:
April 5,
2009
Received:
February 13,
2009
Footnotes
Supported by the Agency for Healthcare Research and Quality (Contract No. 290-02-0021), which suggested the initial questions and provided copyright release for the manuscript, and NIH-R01DK063300-01A2 (to T. J. W., H. A. F., and R. M.)
The authors of this report are responsible for its content. Statements in the report should not be construed as endorsement by the Agency for Healthcare Research and Quality or the United States Department of Health and Human Services
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Copyright
© 2009 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
