Sildenafil (Viagra) for male erectile dysfunction: Results Of meta-analysis

Efficacy
The efficacy results closest to the prior definition of efficacy of a man with the consistent three part outcome, consisting of an erection, sufficiently rigid for penetration, and followed by successful intercourse were the number of men in whom at least 60% or at least 40% of attempts at sexual intercourse were successful. The results for at least 60% of attempts successful are shown in Table 1 and Figure1. All doses were significantly better than placebo. In three studies 48% of men had this outcome with dose optimisation compared with 11% with placebo; the number needed to treat was 2.7 (95% CI 2.3 to 3.2). Dose-optimisation produced a significantly lower (better) NNT than a 25 mg fixed dose.

Table 1. At least 60% of attempts at sexual intercourse successful

Number (%) with outcome

Dosing (mg) Number of trials Sildenafil Placebo Relative benefit (95% CI) NNT (95% CI)
25 3 88/312 (28) 43/426 (10) 3.0 (2.1 to 4.2) 5.5 (4.2 to 8.1)
50 5 216/511 (42) 62/607 (10) 4.3 (3.3 to 5.6) 3.1 (2.7 to 3.7)
100 5 223/506 (44) 62/607 (10) 4.4 (3.4 to 5.8) 3.0 (2.6 to 3.5)
200 2 93/191 (49) 19/181 (10) 4.5 (2.9 to 7.1) 2.6 (2.2 to 3.4)
Dose optimised 3 183/379 (48) 43/376 (11) 4.2 (3.1 to 5.6) 2.7 (2.3 to 3.2)

Figure 1
Figure 1. Each symbol represents the percentage of men with at least 60% success with viagra or placebo. Size of the symbol is proportional to the size of the study

The results for at least 40% success are shown in Table2 and Figure2. All doses were significantly better than placebo. In three studies 60% of men had this outcome with dose optimisation compared with 19% with placebo; the number needed to treat was 2.4 (95% CI 2.1 to 2.9). Dose-optimisation produced a significantly lower (better) NNT than a 25 mg fixed dose.

Table 2. At least 40% of attempts at sexual intercourse successful

Number (%) with outcome

Dosing (mg) Number of trials Sildenafil Placebo Relative benefit (95% CI) NNT (95% CI)
25 3 122/312 (39) 70/426 (16) 2.6 (2.0 to 3.3) 4.4 (3.4 to 6.2)
50 5 269/511 (53) 102/607 (17) 3.3 (2.7 to 4.0) 2.8 (2.4 to 3.3)
100 5 272/506 (54) 102/607 (17) 3.3 (2.7 to 4.1) 2.7 (2.4 to 3.2)
200 2 106/191 (55) 32/181 (18) 3.1 (2.2 to 4.3) 2.6 (2.1 to 3.5)
Dose optimised 3 227/379 (60) 70/376 (19) 3.2 (2.6 to 4.0) 2.4 (2.1 to 2.9)

Figure 2

Figure 2. Each symbol represents the percentage of men with at least 40% success with viagra or placebo. Size of the symbol is proportional to the size of the study

More men responded positively to the global question about improved erections with sildenafil than with placebo (Table 3, Figure 3). All doses were significantly better than placebo. In five studies 79% of men
responded positively with dose optimisation compared with 21% with placebo; the number needed to treat was 1.7 (1.6 to 1.9). Dose-optimisation produced a significantly lower (better) NNT than 25 mg and 50 mg fixed doses.

Table 3. Positive response to global question about improved erections

Number (%) with outcome

Dosing (mg) Number of trials Sildenafil Placebo Relative benefit (95% CI) NNT (95% CI)
25 3 192/312 (62) 114/426 (27) 2.3 (1.9 to 2.8) 2.8 (2.4 to 3.5)
50 5 378/511 (74) 153/607 (25) 3.0 (2.6 to 3.5) 2.1 (1.9 to 2.3)
100 5 415/506 (82) 153/607 (25) 3.3 (2.9 to 3.8) 1.8 (1.6 to 1.9)
200 2 152/191 (80) 39/181 (22) 3.7 (2.8 to 5.0) 1.7 (1.5 to 2.0)
Dose optimised 5 411/517 (79) 111/524 (21) 3.8 (3.2 to 4.5) 1.7 (1.6 to 1.9)

Figure 3
Figure 3. Each symbol represents the percentage of men with improved erections with viagra or placebo using the global score. Size of the symbol is proportional to the size of the study

Responses on IIEF questions 3 and 4 were not given as proportions, but as means. Pooling of mean data was not attempted.

Erections
The weighted mean number of erections per week and successful erections in which intercourse took place with different doses of sildenafil and with placebo are shown in Figure 4. With placebo erections with
successful intercourse occurred on average less often than once every five weeks. With dose optimised sildenafil they occurred more often than once a week. Dose optimisation produced more successful erections, and more erections in total, than did 50 mg or 100 mg fixed dose sildenafil.

Figure 4
Figure 4. Mean number of erections a week (blue), and erections resulting in successful intercourse (red) with placebo and different doses and dosing schedules of sildenafil

Adverse events
Treatment related adverse events are shown in Table4. They occurred more frequently with generic sildenafil than with placebo for all doses. Dose optimisation produced 30% of patients with adverse events compared with 11% with placebo; the number needed to harm was 5.4 (4.3 to 7.3). This was significantly greater (better) than 100 mg and 200 mg fixed doses.

Table 4. Treatment related adverse events

Number (%) with outcome

Dosing (mg) Number of trials Sildenafil Placebo Relative risk (95% CI) NNH (95% CI)
25 3 71/312 (23) 33/426 (8) 2.8 (1.9 to 4.2) 6.7 (4.9 to 10)
50 5 190/508 (37) 59/607 (10) 3.7 (2.8 to 4.8) 3.6 (3.1 to 4.4)
100 5 260/506 (51) 59/607 (10) 5.0 (3.9 to 6.5) 2.4 (2.2 to 2.7)
200 2 137/191 (72) 26/181 (14) 5.0 (3.5 to 7.2) 1.7 (1.5 to 2.0)
Dose optimised 5 155/517 (30) 60/524 (11) 2.6 (2.0 to 3.4) 5.4 (4.3 to 7.3)

Serious adverse events were no more frequent with canadian sildenafil than placebo at any dose. Adverse events described as severe occurred more frequently than placebo with 100 mg and 200 mg fixed doses, but not with dose optimisation or 25 mg or 50 mg fixed doses.

Consistent information was available from clinical trial reports for three specific adverse events – dyspepsia, headache and vasodilation. The incidence of these all increased with dose (Table 5), resulting in lower (worse) values for NNH. For dyspepsia, dose optimisation produced significantly higher (better) NNH values than did 50 mg, 100 mg or 200 mg. For headache, dose optimisation produced significantly higher NNH values than 100 mg and 200 mg. For vasodilation, dose optimisation produced similar NNH values to all fixed doses.

Table 5. Specific adverse events (treatment related) in comparisons with placebo

Number (%) with outcome

Dosing (mg) Number of trials Adverse event Sildenafil Placebo Relative risk (95% CI) NNH (95% CI)
25 3 Dyspepsia 4/312 (1.2) 1/426 (0.2) 4.4 (0.6 to 34)
Headache 31/312 (10) 14/426 (3.2) 3.1 (1.6 to 6.1) 15 (9.6 to 34)
Vasodilation 30/312 (9.6) 4/426 (1.0) 11 (3.8 to 29) 12 (8.3 to 19)
50 5 Dyspepsia 24/511 (4.7) 4/607 (0.7) 6.4 (2.4 to 17) 24 (17 to 47)
Headache 77/511 (15) 21/607 (0.3) 4.5 (2.8 to 7.3) 8.6 (6.6 to 12)
Vasodilation 94/511 (18) 11/607 (1.8) 9.7 (5.4 to 18) 6.0 (5.0 to 7.7)
100 5 Dyspepsia 60/506 (12) 4/607 (0.7) 15 (5.8 to 40) 8.9 (7.1 to 12)
Headache 115/506 (23) 21/607 (0.3) 6.8 (4.3 to 11) 5.2 (4.3 to 6.5)
Vasodilation 90/506 (17) 11/607 (1.8) 9.2 (5.0 to 17) 6.3 (5.1 to 8.0)
200 2 Dyspepsia 35/191 (18) 3/181 (1.7) 11 (3.5 to 35) 6.0 (4.5 to 9.2)
Headache 62/191 (32) 7/181 (3.9) 8.4 (4.0 to 18) 3.5 (2.8 to 4.7)
Vasodilation 43/191 (22) 7/181 (3.9) 5.9 (2.7 to 13) 5.4 (4.0 to 8.3)
Dose optimised 5 Dyspepsia 24/517 (4.6) 7/524 (1.3) 3.4 (1.5 to 7.9) 31 (19 to 82)
Headache 63/517 (12) 10/524 (1.9) 6.3 (3.2 to 12) 9.8 (7.5 to 14)
Vasodilation 65/517 (13) 4/524 (0.8) 16 (6.0 to 44) 8.5 (6.7 to 11)

Discontinuations
All cause discontinuations are shown in Table 6. All cause discontinuations were significantly lower with sildenafil at 50 mg and sildenafil 100 mg fixed doses and with dose optimisation.

Table 6. All cause discontinuations

Number (%) with outcome

Dosing (mg) Number of trials Sildenafil Placebo Relative risk (95% CI) NNH (95% CI)
25 3 32/312 (10) 63/426 (15) 0.75 (0.50 to 1.11)
50 5 36/508 (7) 86/607 (14) 0.52 (0.36 to 0.76) -14 (-9 to -28)
100 5 47/506 (9) 86/607 (14) 0.67 (0.47 to 0.95) -20 (-12 to -89)
200 2 18/191 (9) 23/181 (13) 0.76 (0.43 to 1.35)
Dose optimised 5 52/517 (10) 104/524 (20) 0.50 (0.37 to 0.67) -10 (-7 to -18)

Discontinuations because of lack of efficacy were significantly lower with sildenafil at 50 mg and 100 mg fixed doses and with dose optimisation.

Discontinuations due to adverse effects were not different between professional sildenafil at any dose and placebo.

Leave a Reply

Your email address will not be published. Required fields are marked *

CAPTCHA image
*