Table 1 Summary of characteristics of included studies
Authors (year) place | Study type | Intervention and Comparator | Sample size and age profile | Inclusion criteria | Follow-up period | Measured outcome | Sponsors |
|---|---|---|---|---|---|---|---|
ALLHAT (2003) [47] US, CA, PR | Randomized double-blind controlled trial | Doxazosin 2, 4 or 8 mg/d vs. chlorthalidone 12.5 or 25 mg/d | Doxazosin: n = 9,061 ≥ 70 y: 3,092 Chlorthalidone: n = 15,255 ≥ 70 y: 5,410 | Age ≥ 55 y RRsys ≥ 140 mmHg or RRdia ≥ 90 mmHg or antihypertensive medication  ≥ 1 additional risk factor for cardiac heart disease (CHD) | Mean: 3.2 years | Primary outcome: combined incidence of fatal CHD or nonfatal myocardial infarction Secondary outcome: mortality, combined CHD, stroke, combined cardiovascular disease (CVD) | National Heart, Lung, and Blood Institute (US) Medications by Pfizer Inc, AstraZeneca, Bristol-Myers Squibb Financial support by Pfizer Inc |
Buzelin et al. (1997) [57] FR, BE, DE, NL, DK | Meta-analysis based on 2 RCTs | SR alfuzosin 2 × 5 mg/d vs. placebo | SR alfzusosin: n = 292 ≥ 65 y: 149 Placebo: n = 296  ≥ 65 y: 153 | LUTS due to BPH > 6 months Nocturia: ≥ 2 and/or Day-time frequency: ≥ 8 Qmax: ≤ 15 ml/s Voiding volume: > 150 ml | 1 month | All ADEs with a special focus on ADEs related to vasodilatory events | N.a. |
Chapple et al. (1997) [59] BE, DE, DK, NL, NO, SE, UK | Meta-analysis based on 2 double-blind RCTs | Tamsulosin 0.4 mg/d vs. placebo | Tamsulosin: < 65 y: 190  ≥ 65 y: 191 Placebo: < 65 y: 93 ≥ 65 y: 100 | Age ≥ 45 y LUTS due to BPH 4 ml/s ≤ Qmax ≤ 12 ml/s Voiding volume: ≥ 120 ml Boyarsky score > 6 | 12 weeks | ADEs | Yamanouchi Europe BV |
Chrischilles et al. (2001) [50] US | Retrospective cohort study | Alpha-1 antagonist users (terazosin/ doxazosin/ prazosin) vs. non-users | Users: n = 1,564 Mean age: 73 y Prazosin = 15 Doxazosin = 782 Terazosin = 839 Non-Users: n = 8,641 Mean age: 72.5 y | Age ≥ 65 y Diagnosed BPH | 4 months | Possibly hypotension related adverse effects (e.g. hypotension, syncope, dizziness, falls) | Grant from Boehringer Ingelheim |
Duan et al. (2018) [33] US | Retrospective Cohort Study | Tamsulosin vs. each of the following: No BPH medication Doxazosin Terazosin Alfuzosin Dutasteride Finasteride | Tamsulosin: n = 253,136 No BPH-medication: n = 180,926 Doxazosin: n = 28,581 Terazosin: n = 23,858 Alfuzosin: n = 17,934 Dutasteride: n = 34,027 Finasteride: n = 38,767 | Age ≥ 66 y Diagnosed BPH | Median follow-up: 19.8 months | Incidence of dementia | Connecticut Institute for Clinical and Translational Science Patient-Centred Outcome Research Trust Fund |
Gotoh et al. (2005) [35] JP | Randomized controlled trial | Tamsulosin 0.2 mg/d vs. naftopidil 50 mg/d | Tamsulosin: n = 75 mean age: 68.5 y 95% CI: 67.0 – 70.1 y Naftopidil: n = 69 mean age: 68.0 y 95% CI: 66.4 – 69.8 y | Age ≥ 50 y Symptomatic BPH IPSS ≥ 8 Qmax < 15 ml/s Voiding volume ≥ 150 ml Vprostate: ≥ 20 ml | 12 weeks | Primary outcomes: changes in IPSS, Qmax and residual urine volume Secondary outcomes: average flow rate, changes in IPSS storage score and IPSS voiding score, quality-of-life score | N.a. |
Hall and McMahon (2007) [52] UK | Case–control study | Fracture vs. no fracture | Cases (fracture): n = 6,540 Taking MR Doxazosin: 66 Taking MR Doxazosin and ≥ 75y: 32 Controls (no fracture): n = 26,495 Taking MR Doxazosin: 311 Taking MR Doxazosin and ≥ 75y: 173 | Age ≥ 50 y Cases: Fracture of hip/femur, humerus, wrist Mean age: 74 y Controls: No fracture Mean age: 73 y Matched with Cases on primary care practice, year of birth and sex | Mean (SD) days of observation: Cases: 569 (344) Controls: 569 (344) | Incidence of fracture of hip, femur, humerus and/or wrist | Pfizer UK |
Hiremath et al. (2019) [54] CA | Retrospective cohort study | Alpha-1 antagonist users (terazosin, prazosin, doxazosin) vs. other BP lowering medication users | Users: n = 14,106 Mean age: 75.7 y Non-Users: n = 14,106 Mean age: 75.7 y | Age ≥ 66 y Only women No previous alpha-1 antagonist use < 6 BP lowering medications | 12 months | Primary outcomes: hypotension and related events (syncope, falls, fractures) Secondary outcomes: adverse cardiac events, all-cause mortality | Supported by the Institute for Clinical Evaluative Sciences (ICES) ICES is funded by Ontario Ministry of Health and Long-Term Care Data partly provided by CIHI |
Hundemer et al. (2021) [32] CA | Retrospective cohort study | Alpha-1 antagonist users (terazosin, prazosin, doxazosin) vs. other BP lowering medication | Exposed: n = 16,088 Mean age: 75 y Not exposed: n = 16,088 Mean age: 75 y | Age ≥ 66 y Diagnosis of hypertension New prescription for alpha-1 antagonists/ other BP lowering drug | Max. 3 y | Adverse kidney events, cardiac events, all-cause mortality, ADEs (hypotension, syncope, falls, fractures) | Supported by the Institute for Clinical Evaluative Sciences (ICES) ICES is funded by Ontario Ministry of Health and Long-Term Care Data partly provided by CIHI |
Lowe (1994) [58] US, EU | Meta-analysis based on 6 double-blind RCTs | Terazosin 1–20 mg/d vs. placebo | Terazosin: n = 636 ≥ 65 y: 285 Placebo: n = 360 ≥ 65 y: 162 | Symptomatic BPH Qmax: ≤ 12 ml/s Min. voiding volume: 100–150 ml | 2–6 months | ADEs | Grant from Abbott Laboratories |
Nishino et al. (2006) [36] JP | Randomized crossover trial | Tamsulosin 0.2 mg/d vs. naftopidil 50 mg/d | Tamsulosin/ naftopidil: n = 17 Naftopidil/tamsulosin: n = 17 | Age ≥ 66 y Symptomatic BPH IPSS ≥ 8 Qmax: ≤ 15 ml/s No prior treatment for BPH | 9 weeks (two 4-week trials for each substance and a 1-week washout in between) | IPSS, QoL score, uroflowmetry, pressure flow study | Gifu University, JP |
Oelke et al. (2014) [48] AU, AT, BE, FR, DE, GR, IT, MX, NL, PL | Randomized double-blind placebo-controlled trial | Tamsulosin 0.4 mg/d vs. tadalafil 5 mg/d vs. placebo | Tamsulosin: n = 168 ≥ 66 y: 72 Tadalafil: n = 171 ≥ 66 y: 75 Placebo: n = 172 ≥ 66 y: 77 | Age ≥ 45y Symptomatic BPH > 6mo IPSS ≥ 13 Qmax: 4–15 ml/s PVR < 300 ml No treatment with finasteride within 3mo No treatment with dutasteride within 6mo | 12 weeks | Treatment Satisfaction Scale-BPH (TSS-BPH) | Eli Lilly and Company Personal fees from diverse pharma-ceutical companies for authors Three authors employed by Eli Lilly and Company during conduct of study |
Roehrborn (2006) [49] North America, Australia, Middle East, South Africa, Europe | Randomized double-blind placebo-controlled trial | Alfuzosin 10 mg/d vs. placebo | Alfuzosin: n = 759 ≥ 65 y: 449 Placebo: n = 763 ≥ 65 y: 439 | Age ≥ 55y Symptomatic BPH ≥ 6mo IPSS ≥ 13 Qmax: 5–12 ml/s Voiding volume ≥ 150 ml PVR ≥ 350 ml Vprostate: ≥ 30 g | 24 months | Primary outcome: Occurrence of first period of acute urinary retention Secondary outcomes: BPH-related surgery, total IPSS, bother score, Qmax | Sanofi-Aventis |
Siemens et al. (2021) [55] CA | Retrospective cohort study | No medication vs. dutasteride or finasteride (5-ARI) use vs. silodosin or tamusosin (selective) or terazosin or alfuzosin or doxazosin (non-selective alpha-1 antagonist) use vs. 5-ARI + alpha-1 antagonist use | No medication: n = 69,988 Mean age: 74.05 y Alpha-1 antagonist: n = 55,383 Mean age: 74.26 y 5-ARI + alpha-1 antagonist: n = 41,491 Mean age: 74.11 y | Age ≥ 66 y Diagnosis of BPH No recent history of cardiac failure | Max. 13 y | Incidence of heart failure | Supported by the Institute for Clinical Evaluative Sciences (ICES) ICES is funded by Ontario Ministry of Health and Long-Term Care Data provided by CIHI |
Tae et al. (2019) [56] KR | Retrospective cohort study | Analysis 1: Tamsulosin vs. each of the following: Doxazosin Terazosin Alfuzosin Analysis 2: No medication vs. each of the following: Tamsulosin Doxazosin Terazosin Alfuzosin | No medication: n = 3,336 Mean age: 77.03 y Tamsulosin: n = 33,568 Mean age: 76.47 y Doxazosin: n = 7,012 Mean age: 76.54 y Terazosin: n = 9,443 Mean age: 76.73 y Alfuzosin: n = 5,904 Mean age: 76.14 y | Age ≥ 70 y Diagnosis of BPH No factors associated with cognitive decline (e.g. chemotherapy, anticholinergic drug use or psychiatric disease) | Mean (SD) days of follow up: 1,580 (674) | Incidence of dementia | Grant from Korea University and the Korea Urologic Association |
Testa et al. (2018) [53] IT | Case–control study | Syncopal fall vs. non-syncopal fall | Syncopal fall: n = 354 Mean age: 83.3 y Non-syncopal fall: n = 168 Mean age: 83.9 y | Age ≥ 65 y Dementia ≥ 1 transient loss of consciousness or unexplained fall within previous 3 months | 3 months | Orthostatic hypotension related syncopal falls | Endorsement of Italian Society of Gerontology and Geriatrics |
Welk et al. (2015) [51] CA | Retrospective cohort study | Tamsulosin, silodosin, alfuzosin vs. no alpha-blocker treatment | Alpha-blocker initiation: n = 147,084 No initiation: n = 147,084 | Age ≥ 66 y Alpha-1 antagonist cohorts: Initiation of first treatment with tamsulosin, silodosin, or alfuzosin Non-alpha-1 antagonist cohort: Unexposed to alpha-blocker Matched on age, residential status, prior fractures, use of 5α-reductase inhibitors | 90 days | Primary outcome: hospitalization for a fall or fracture within 90 days after initiation of alpha-blocker therapy Secondary outcomes: hypotension, head trauma | Institute for Clinical Evaluative Sciences (Ontario Ministry of Health and Long-Term Care) |
Yokoyama et al. (2011) [34] JP | Randomized controlled trial | Tamsulosin 0.2 mg/d vs. silodosin 8 mg/d vs. naftopidil 50 mg/d | Tamsulosin: n = 45 mean age: 71.5 y Silodosin: n = 45 mean age: 70.2 y Naftopidil: n = 46 mean age: 69.1 y | Age ≥ 50 Symptomatic BPH PSS ≥ 8 | 12 weeks | IPSS, quality-of-life score, International Index of Erectile Function (IIEF-5), Qmax, PVR | N.a. |