Sildenafil for erectile dysfunction: 2005 update

Clinical bottom line

Sildenafil has been studied in a large number of men, with many different causes of their erectile dysfunction, and in different parts of the world. At the top fixed doses of 50 or 100 mg, or in the dose-optimised schedule of 25-100 mg, it has considerable efficacy, with a number needed to treat below 2, and 76% of men have improved erections. Headache (17%), flushing (13%), dyspepsia (8%), and rhinitis (5%) were the most common individual adverse events, though few men discontinued because of adverse events.

Reference

RA Moore et al. Indirect comparison of interventions using published randomised trials: Systematic review of PDE-5 inhibitors for erectile dysfunction. BMC Urology 2005 2005, 5:18.

Systematic review

Randomised trials were sought of three PDE-5 inhibitors (sildenafil, tadalafil, vardenafil), with placebo or active comparator, in men with erectile dysfunction of any causation, with drugs used at home. Previous systematic reviews were used to source trials or trial data, supplemented by electronic searches of PubMed (to June 2005, and supplemented by searches to November 2005 for this update) and the Cochrane Library (issue 1, 2005) using drug names and randomis(z)ed trial.

Information extracted was of efficacy, using a number of different efficacy outcomes, discontinuations, and specific adverse events. Because various dosing regimens were used, including fixed doses, and dose-optimised regimens, and because there was a similarity of result for the top two fixed doses (50 and 100 mg) and dose optimised (25-100 mg, where most men used 50 or 100 mg), results here include all studies reporting on 50 mg, 100 mg, or dose optimised regimens.

Date review completed: June 2005, updated November
Number of trials included: Maximum data on 30 trials, but 37 in all
Number of patients: 5,599 men in largest analysis, but 7,500 men in total
Control groups: Placebo
Main outcomes: Improved erections, IIEF, discontinuations, specific adverse events

Results

None of the trials used an active comparator, and most scored highly on reporting quality. All were randomised and double blind for inclusion in the review. Most studies were in men with erectile dysfunction of mixed aetiology, and trials were also conducted in men with diabetes, depression, spinal cord injury, coronary heart disease, radiotherapy for prostate cancer, renal failure and haemodialysis, rectal surgery, and spina bifida. Studies were conducted worldwide, including Europe, North and South America, Asia, and Africa.

Erectile function

With sildenafil 50/100 mg, the erectile function domain score rose to 22 (compared with 14 for placebo), an average 10-point change. Successful attempts at intercourse occurred 65% of the time, compared with 23% with placebo.

On average, in 5599 men in 30 trials, 76% of men reported improved erections, compared with 23% with placebo (Figure 1). The number needed to treat for one man to have improved erections compared with placebo was 1.9 (95% confidence interval 1.8 to 2.0; Table 1).

Figure 1: Improved erections in comparisons of sildenafil and placebo

Table 1: Efficacy and adverse event outcomes in comparisons of sildenafil and placebo

	Number of		Percent with
Outcome	Trials	Patients	Sildenafil	Placebo	Relative benefit or risk (95% CI)	NNT/NNTp/NNH (95% CI)
Efficacy
Improved erections	30	5599	76	23	3.3 (3.1 to 3.6)	1.9 (1.8 to 2.0)
Discontinuation
All-cause	29	5343	8.2	12	0.7 (0.6 to 0.8)	28 (19 to 50)
Lack of efficacy	29	5228	1.2	4.4	0.3 (0.2 to 0.5)	32 (25 to 45)
Adverse event	30	5554	1.6	0.6	1.8 (1.2 to 2.7)	110 (64 to 450)
Adverse events
All cause	17	2634	49	29	1.7 (1.5 to 1.8)	4.9 (4.2 to 6.0)
Serious	16	2364	1.6	1.6	1.0 (0.6 to 1.7)	not calculated
Headache	33	6166	17	5.2	3.3 (2.8 to 3.9)	8.8 (7.7 to 10)
Dyspepsia	25	4740	7.9	2.4	3.2 (2.4 to 4.3)	18 (15 to 24)
Flushing	32	6135	13	1.7	6.6 (5.1 to 8.5)	9.1 (8.2 to 10)
Rhinitis	20	4057	5.4	1.8	2.4 (1.7 to 3.4)	32 (23 to 50)
NNT is given in standard font, NNTp in bold, and NNH in bold italic. No NNT/NNTp/NNH was calculated unless there was a statistically significant difference

Adverse events

All-cause discontinuation and lack of efficacy discontinuation were less frequent with sildenafil than placebo, but adverse event discontinuation more frequent. About 1% more men discontinued because of adverse events with sildenafil than with placebo (Table 1).

About half of men had some adverse event, but serious adverse events were no more common with sildenafil than with placebo in these trials. Headache (17%), flushing (13%), dyspepsia (8%), and rhinitis (5%) were the most common individual adverse events.

Comment

Sildenafil has been studied in a large number of men, with many different causes of their erectile dysfunction, and in different parts of the world. At the top fixed doses of 50 or 100 mg, or in the dose-optimised schedule of 25-100 mg, it has considerable efficacy, with a number needed to treat below 2. To have such good efficacy despite the wide range of conditions studied indicates a robust result.