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Keywords:

  • dropout rate;
  • IIEF-5;
  • sildenafil

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References

Objectives:  To study the dropout rate for use of sildenafil after initial prescription and during successful treatment to clarify their risk factors.

Methods:  A total of 1036 patients with erectile dysfunction who were treated with sildenafil were analyzed. The dropout rate during successful treatment and its risk factors were assessed using the Kaplan–Meier method and Cox proportional hazards model, respectively.

Results:  Thirty-one percent (n = 322) of the patients dropped out after the initial prescription. The cumulative dropout rate during successful treatment at 3 years after starting usage was 48%. A lower International Index of Erectile Function (IIEF-5) score before treatment was a significant risk factor for dropout during a successful treatment course (P < 0.029 by the Cox proportional hazards model).

Conclusions:  Approximately 30% and 50% of the patients dropped out of treatment after the first prescription and at 3-year follow-up, respectively. Adequate initial instruction and long-term follow-up are required even for patients with successful treatment.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References

Sildenafil, the first phosphodiesterase 5 inhibitor (PDE5-I), has achieved great success for treatment of erectile dysfunction (ED).1–3 Other PDE5-Is also have similar successful outcomes.4,5 These epoch making-drugs improve the quality of life (QOL) of ED patients.6,7 Many well-controlled clinical trials have revealed the efficacy and safety of the drugs for the various etiological subgroups of ED. The overall efficacy is around 80% for ED with a low prevalence of adverse events.1–5,7 Despite such good outcomes of PDE5-Is, discontinuation of treatment often occurs in the ‘real life’ setting.8–11 The ED patients and their partners who were involved in the clinical trials were specialized from a certain point of view. These patients were highly motivated, well educated, and medication was free of cost.12 In contrast to these first class-ED patients, ED-patients in real life may encounter various problems with successful treatment.8–11 Even patients who achieve successful outcomes may gradually drop out. Unfortunately, we do not have enough data concerning these dropout rates with long-term follow-up in our country Japan.

In this regard, our goals were to clarify the dropout rates after the first prescription of the drug and during successful treatment with time after starting the drug and to analyze the risk factors associated with dropout. From a different point of view, we also considered the question, how long did ED patients continue sildenafil-treatment during the 6 years after the launch of the drug?

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References

A total of 1036 patients with ED who were treated with sildenafil citrate in Sanjukai Hospital from June 1998 to December 2004 were analyzed for treatment outcomes. The age distribution of the patients is shown in Table 1.

Table 1.  Characteristics of 1036 ED patients treated with sildenafil
Variablen (%)
  1. ED, erectile dysfunction; IIEF, International Index for Erectile Function; RP, radical prostatectomy.

Age (years)
 20–2933 (3.2)
 30–3962 (6.0)
 40–49154 (14.9)
 50–59226 (21.8)
 60–69353 (34.1)
 70+208 (20.1)
ED grade pretreatment according to IIEF-5 score
 Mild291 (28.1)
 Moderate352 (34.0)
 Severe393 (37.9)
Comorbidities
 Diabetes mellitus55 (5.3)
 Hypertension102 (9.4)
 Cardiac disease13 (1.3)
 Ischemic heart disease2 (0.2)
 Arterial sclerosis6 (0.6)
 Cerebrovascular disease20 (1.9)
 Depression19 (1.8)
 Spinal cord injury12 (1.2)
 Prostate cancer/RP19 (1.8)
 Intrapelvic operation (cystectomy/miles ope)17 (1.6)

The medical history of each patient was analyzed based on an interview, a self-administrated questionnaire and physical examination. Pretreatment sexual function was assessed by history taking and International Index of Erectile Function 5 (IIEF-5). ED severity was classified according to IIEF-5 score into mild (score 17–21), moderate (score 8–16), and severe (score 1–7).13 The distribution of ED severity is shown in Table 1. Blood examinations, including hormonal examination, were performed according to the ISSM recommendations.14 Patients with various etiologies of ED according to these initial examinations were involved in this study (Table 1). Sildenafil was chosen as the first line therapy according to the ISSM recommendations on the treatment strategy for erectile dysfunction.14

Patients who did not visit the hospital after the first prescription were defined as dropouts after first prescription. Patients who continued to visit the hospital were evaluated for drug efficacy. Treatment success was defined as the achievement of satisfactory sexual intercourse with an adequate dose of the drug. Treatment failure was defined as the impossibility of having sexual intercourse in several attempts with dose escalation of the drug. When a patient with successful treatment did not visit the hospital for more than 1 year after the last prescription of the drug, he was considered a dropout.

The dropout rate after the first prescription, rate of successful treatment and dropout rate of successfully treated patients during the treatment course were analyzed (Fig. 1). We could not ask the patients for reasons for dropouts because of the patients’ privacy concerns.

image

Figure 1. Treatment scheme for 1036 patients who received sildenafil treatment.

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Statistical analysis

The dropout rate after first prescription, treatment success and failure on each age decade were analyzed by Kruskal–Wallis test. Pretreatment IIEF-5 scores of these three groups were analyzed by anova. Significant risk factors for the dropout during successful treatment were analyzed by the Cox proportional hazards model. In this model, dropout was a dependent variable; independent variables were the pretreatment age, IIEF-5 score, and status of comorbidities. Kaplan–Meier curves were used for the dropout rates of total and mild, moderate and severe ED groups based on results of the Cox proportional hazards model. The dropout rates of the three groups were statistically analyzed using the log-rank test. Statistical significance was defined as P < 0.05.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References

Dropout rate after first prescription of the drug

As shown in Figure 1, 31% (n = 322) of patients dropped out after the first prescription of the drug. The remaining 69% of patients (n = 714) continued to visit the hospital. Of all patients, 64% were confirmed to have treatment success and 5% to have failure (Fig. 1). There were no significant differences among the distributions of treatment outcomes in each age decade (Fig. 2). IIEF-5 scores of the dropouts after the first prescription, success and failure groups are shown in Figure 3. The dropout after the first prescription group had lower IIEF-5 scores than the treatment success group and higher IIEF-5 scores than the failure group.

image

Figure 2. Distribution of treatment outcomes in each age decade showing no significant differences analyzed by Kruskal–Wallis test (P = 0.219).

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image

Figure 3. Mean ± SD pretreatment International Index for Erectile Function (IIEF-5) scores for each treatment outcome. anova revealed significant differences among the three groups (P < 0.0001). Each value has a significant difference compared to other groups by Fisher’s post hoc test. *P = 0.0017; **P < 0.0001; ***P < 0.0001.

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Dropout rate during successful treatment

Patients with successful outcomes gradually dropped out and 48% of the patients had dropped out at 3 years (Fig. 4). In the Cox proportional hazards model, the pretreatment IIEF-5 score was a significant risk factor for dropout (Table 2). Then we analyzed the dropout rate of successful cases depend on ED severity (mild, moderate and severe ED) corresponding to the pretreatment IIEF-5 scores. There was a significant difference in the dropout rate among the three groups, with patients in the severe ED group most likely to drop out (Fig. 4).

image

Figure 4. Kaplan–Meier dropout rate in all successful treatment cases and dependence on severity of erectile dysfunction (ED). There were significant differences in ED severity by the log-rank test (P = 0.029).

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Table 2.  Cox hazard model for dropout rate of success cases
FactorsHazard ratio (95% CI)P
  1. CI, confidence interval; IIEF, International Index for Erectile Function.

IIEF-5 score0.960 (0.931–0.990)0.025
Age0.992 (0.982–1.001)0.164
Complication1.037 (0.765–1.407)0.808

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References

This study clearly demonstrates that a significant percentage of the ED patients who were treated with sildenafil dropped out after the first prescription of the drug and during successful treatment. ED patients treated with PDE5-Is may encounter various problems in addition to insufficient pharmacological effects, including relationship problems and loss of sexual interest.8–11 These problems may cause the patients to drop out of treatment; however, except for insufficient pharmacological effects, these problems were not clearly demonstrated in the clinical trials and extended studies because participants were well-selected and educated.12 Thus, the dropout rates in the present study may indicate one aspect of the real outcomes of sildenafil treatment in our country. However, ED patients continued to use sildenafil for 3 years on average. This confirms the significant contribution of sildenafil to improvement of the quality of life of ED patients.

This study did not provide direct reasons for dropping out. We cannot deny that a certain percentage of dropped out patients may continue to use the drug, obtaining it through other hospitals and/or the Internet. Although this study has such limitations, the results provide useful information and clinical suggestions.

Around 30% of patients in our series dropped out after the first prescription for the medicine. Interestingly, these initial dropouts had significantly higher pretreatment IIEF-5 scores than failed treatment patients who were confirmed pharmacologically to be non-responders. Thus, these initial dropouts occurred not only because of insufficient pharmacological effects but also non-treatment-related reasons. Previous reports indicated that inadequate instruction might be involved in treatment failure9 and re-education increased the number of responders.12,15 Several attempts using the drug may be required to obtain satisfactory sexual intercourse.12 Therefore improvement of the instruction about drug use may reduce the dropout rate after the first prescription and maximize the potential of the drug.

The dropout rate of patients having successful treatment increased with time. At 3 years after starting treatment, about 50% of patients had dropped out. In a long-term open label study 32% of enrolled patients dropped out within 3 years.2 A study from the Netherlands showed that 45% of all patients discontinued sildenafil treatment during the median follow-up period of 18 months.10 A low IIEF-5 score was a significant risk factor for dropout during a successful treatment course. This finding suggests that dropout during successful treatment may be associated with a gradual decline of erectile function and/or sexual activity. In patients with low IIEF-5 scores, drug efficacy and/or sexual activity may tend to be lost earlier than in patients with relatively better erectile function. However, patients with mild ED also showed a similar tendency to drop out. Thus non-treatment-related reasons may be involved in the time-related increment of dropout as previous reports suggested. Souverein et al. reported that about 80% of discontinuation was not treatment related.10 Insufficient responses and adverse events accounted for about 17% and 4% of treatment-related discontinuations, respectively. Kolt et al. reported that the major reasons for abandoning effective therapy with sildenafil were lack of opportunities or desire for sexual intercourse and the partner’s lack of sexual interest.8

Many biopsychosocial obstacles to sexual intercourse exist in real life situations and may impede successful outcomes.11 For pharmacological reasons, appropriate initial instruction, re-education, adequate dose-titration and changes of treatment methods during follow-up would be effective.9,13,14 Appropriate consultation during follow-up may alleviate non-treatment-related problems. We should always be aware of the importance of these factors in order to achieve better outcomes in the ‘real life’ situation.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References
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