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Direct Comparison of Tadalafil with Sildenafil for the Treatment of Erectile Dysfunction: a Systematic Review and Meta-Analysis

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Direct Comparison of Tadalafil with Sildenafil for the Treatment of Erectile Dysfunction: a Systematic Review and Meta-Analysis Int Urol Nephrol DOI 10.1007/s11255-017-1644-5 UROLOGY - ORIGINAL PAPER Direct comparison of tadalafl with sildenafl for the treatment of erectile dysfunction: a systematic review and meta‑analysis Binbin Gong1 · Ming Ma1 · Wenjie Xie1 · Xiaorong Yang1 · Yongming Huang1 · Ting Sun1 · Yanping Luo1 · Jiao Huang1 Received: 29 April 2017 / Accepted: 26 June 2017 © The Author(s) 2017. This article is an open access publication Abstract adherence and persistence rates between tadalafl and silde- Aims Erectile dysfunction (ED) is a major care problem nafl. Additionally, the myalgia and back pain rates were worldwide. Tadalafl and sildenafl are the two most common higher and the fushing rate was lower with tadalafl than phosphodiesterase 5 inhibitors used to treat ED. This sys- with sildenafl. tematic review and meta-analysis were conducted to directly Conclusion Tadalafl shares a similar efcacy and safety compare tadalafl with sildenafl for the treatment of ED. with sildenafl and signifcantly improves patients’ sexual Methods We designed a strategy for searching the Pub- confdence. Furthermore, patients and their partners pre- Med, Embase, EBSCO, Web of Science and Cochrane fer tadalafl to sildenafl. Hence, tadalafl may be a better library databases; the reference lists of the retrieved studies choice for ED treatment. were also investigated. A literature review was performed to identify all published randomized or non-randomized Keywords Tadalafl · Sildenafl · Erectile dysfunction · controlled trials that compared tadalafl with sildenafl for Meta-analysis · Systematic review the treatment of ED and to assess the quality of the stud- ies. Two investigators independently and blindly screened the studies for inclusion. The meta-analysis was performed Introduction using RevMan 5.0. Results A total of 16 trials that compared tadalafl with Erectile dysfunction (ED) is defned as the inability to sildenafl for the treatment of ED were included in the achieve and maintain an erection sufcient to permit sat- meta-analysis. In the meta-analysis, tadalafl and sildena- isfactory sexual intercourse. ED is one of the most com- fl appeared to have similar efcacies and overall adverse mon sexual dysfunctions, and an estimated 5–20% of men event rates. However, compared with sildenafl, tadalafl are afected by moderate to severe ED around the world [1]. signifcantly improved psychological outcomes. Further- The prevalence of ED is approximately 15.77% in south- more, the patients and their partners preferred tadalafl over ern India, 15.0–49.5% in China, 56.1% in Iran and 58.9% in sildenafl, and no signifcant diference was found in the south-western Nigeria [2–5]. The estimated global preva- lence has been increasing, and approximately 322 million men worldwide could be afected by ED by the year 2025 Binbin Gong and Ming Ma have contributed equally to this article. [6]. Although ED is a benign disorder, it can afect physical and psychosocial health and may have a signifcant impact * Ming Ma on the quality of life of patients and their partners. [email protected] Currently, several treatment strategies are available * Ting Sun for patients with ED, including non-invasive and invasive sunt‑[email protected] options. Oral phosphodiesterase type 5 inhibitors (PDE5- 1 Is) are the frst-line therapy for ED [7]. PDE5-Is are similar Department of Urology, The First Afliated Hospital of Nanchang University, Nanchang 330000, Jiangxi Province, to cyclic guanosine monophosphate (cGMP) in structure; China thus, PED5-Is can bind to PDE5 competitively and inhibit Vol.:(0123456789)1 3 Int Urol Nephrol cGMP hydrolysis, leading to a penile erection [8]. Four and tadalafl remain unclear [13–15]. Hence, this meta- PDE5-Is (sildenafl, tadalafl, vardenafl and avanafl) are analysis was conducted to directly compare sildenafl with currently approved by the US FDA and have comparable tadalafl for the treatment of ED and to provide guidance efcacy and side efect profles [9]. Sildenafl and tadala- for the clinical treatment of ED. fl are the two most common phosphodiesterase inhibitors (PDEIs) around the world. Sildenafl, the original PDEI, was introduced in 1998. Sildenafl has a quick onset of action of 30 min after the initial dose, a duration of action Materials and methods of 4–6 h and a maximum duration of 12 h [10]. Sildenafl is efective for the treatment of ED, although 20–50% of Search strategy patients who respond to sildenafl discontinue its use [11]. Tadalafl is a selective, long-acting PDEI that was released In January 2017, the PubMed, EBSCO, Web of Science, in 2003. Tadalafl has an onset of 20 min and should be Cochrane library and Embase databases were searched for taken 30 min prior to intercourse; additionally, this drug randomized or non-randomized controlled clinic trials of has the longest duration of action in its class and a maxi- sildenafl and tadalafl. The search was performed by com- mum duration of 72 h. A total of 52% of patients can have bining the term “erectile dysfunction or sexual dysfunc- successful intercourse within 30 min of taking tadalafl tion” with the following words describing the drug: tada- [12]. Recently, several systematic reviews and meta-analy- lafl or Cialis and sildenafl or Viagra. We also searched ses have comparatively analysed the role of PDEIs, includ- for additional relevant studies by examining the reference ing sildenafl and tadalafl, in the treatment of ED. How- lists of the selected papers and reviews. The search process ever, because most of these review articles were indirect was not limited by language, country or year of publication. comparative analyses, the diferences between sildenafl The search strategy is presented in Fig. 1. Fig. 1 Flow chart of study selection 1657 records identified through database searching and other sources 529 records after duplicates removed 176 records were excluded: 224 records screened Abstracts and reviews No comparison between tadalafil and sildenafil Duplicates and others 32 full-text articleswere 48 full-text articles assessed excluded: for eligibility Repeated data published Irrelevant outcomes Duplicates and others 16 studieswere included in the meta-analysis 1 3 Int Urol Nephrol Study selection was performed to assess the stability of the outcome when low-quality and highly heterogeneous trials were included For the present systematic review, randomized or non-rand- in the analysis. omized controlled trials that met the following criteria were included: (a) the study included a comparison between sildenafl and tadalafl; (b) the study provided accurate Results data that applied to a meta-analysis, including the Interna- tional Index of Erectile Function (IIEF)-EF domain, prefer- Search results ence and treatment–emergent adverse events (TEAEs); and (c) the full text of the study could be acquired. When the A total of 1657 articles were identifed through the elec- same study was published in diferent journals or in difer- tronic databases and the manual review of the reference ent years, the most recent version was used for the meta- lists of the included studies. Based on the search strategy, analysis. Abstracts, reviews and articles that did not contain a total of 16 studies were included in the review [17–31]. accurate relevant data and a comparative analysis of silde- A total of 5189 patients were recruited in the fnal meta- nafl and tadalafl were excluded. analysis, and the mean patient age ranged from 36.9 to 56.2 years. Seven articles were open-label, randomized, multicentre, controlled studies; nine of the studies had a Quality assessment crossover design; and the other studies were prospective and observational. All the studies compared sildenafl and Two independent reviewers evaluated all identifed pub- tadalafl. The common instruments used to assess these two lications, and any disagreement between reviewers was PDEIs (sildenafl and tadalafl) were the IIEF-EF, prefer- resolved by a third reviewer. The methodological quality ence, TEAEs, adherence and persistence. The characteris- was assessed using the Jadad score, with a Jadad score ≥3 tics of the studies are listed in Table 1. indicating a high-quality article [16]. Efcacy measures Data extraction A meta-analysis was conducted to examine the efcacy Data extractions were performed by one reviewer and of sildenafl and tadalafl. No signifcant diferences were checked by a second reviewer. Information was extracted found in the changes in the IIEF-EF between patients who from the studies that met the above-mentioned inclusion used sildenafl and those who used tadalafl (random efects criteria using a structured form. The frst author, publica- model: WMD: 0.03, 95% CI: −0.32 to 0.39, P = 0.85). tion year, sample size, therapy that the patients received The pooled mean efect size of the IIEF intercourse satis- and assessment indices, including the IIEF, the men’s pref- faction result for tadalafl versus sildenafl was 0.45 (95% erence, the Self-Esteem and Relationship questionnaire CI: −0.96 to 1.86, P = 0.53). Our analysis found hetero- (SEAR), total Erectile Dysfunction Inventory of Treatment geneity among the trials, and a random efects model was Satisfaction (EDITS) scores and TEAEs, were collected for adopted. Similarly, for IIEF overall satisfaction and IIEF each study. sexual desire, the pooled mean efect sizes were 0.00, 95% CI: −0.03 to 0.03, P = 0.98 and 0.00, 95% CI: −0.02 to 0.02, P = 0.99, respectively; neither of these studies exhib- Statistical analysis ited evidence of heterogeneity. Compared with sildenafl, tadalafl signifcantlly improved the SEAR Confdence A meta-analysis of comparable data was performed using (fxed efects model: WMD: 1.26, 95% CI: 1.04–1.45, RevMan 5.0. Statistical heterogeneity between studies was P < 0.00001), SEAR Sexual Relationship (fxed efects assessed using the I2 statistic. Pronounced heterogeneity model: WMD: 1.52, 95% CI: 1.32–1.72, P < 0.00001) and was indicated by a P value ≤0.05 and an I2 value ≥50%; in EDITS total scores (fxed efects model: WMD: 3.82, 95% these cases, a randomized efects model was executed.
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