| Methods |
Randomized, double‐blind, placebo‐controlled trial (parallel groups). 3 x 4 factorial design. Wash‐out period = 4 to 6 weeks. Multicenter, USA |
| Participants |
Sitting DBP 95 to 115mmHg. Mean age: 53 years. Males: 71%. Race: 71% non‐black. Baseline sitting BP was 151/101 mmHg. Sitting heart rate = 76 bpm |
| Interventions |
Bisoprolol 2.5 mg, 10 mg or 40 mg/d (all combined, N = 197), bisoprolol 2.5 mg, 10 mg or 40 mg/d + HCTZ 6.25 mg or 25 mg/d (all combined, N = 190), HCTZ 6.25 mg (N = 29) or 25 mg/d (N = 33), or placebo (N = 63)
Duration = 12 weeks + 2‐week taper period |
| Outcomes |
Mean change from the baseline in trough sitting DBP and SBP at 3 to 4 weeks; analyses of the effects of age, sex, race and baseline DBP on change in BP; serum biochemistry |
| Notes |
A sample size calculation was provided based on 60 patients in the bisoprolol monotherapy group and 30 patients in all others groups to detect a difference of 3.6 to 5.1 mmHg and 5.1 to 7.3 mmHg, respectively, with 80% power. The study authors stated that there were no significant differences across treatment groups in the baseline patient characteristics. SD for BP data not given. BP data at endpoint (i.e. 12 weeks) not reported; midpoint only |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Unclear risk |
"The study reported on here was 12‐week, randomised, double‐blind, placebo‐controlled, multicenter 3x4 factorial trial..." (line 1 under "Methods‐Study Design" p.1462). No further information was given |
| Allocation concealment (selection bias) |
Unclear risk |
Not stated by study authors |
| Blinding (performance bias and detection bias)
All outcomes |
Low risk |
"Patients whose mean sitting diastolic blood pressure was stable and between 95 and 115 mmHg (inclusive) qualified for randomisation to one of 12 double‐blind treatment groups. To maintain blinding, matching placebo tablets were provided for both bisoprolol and hydrochlorothiazide." (line 27 under "Methods‐Study Design" p.1462) |
| Incomplete outcome data (attrition bias)
All outcomes |
High risk |
It is not known whether efficacy analysis was based on an intention‐to‐treat or per‐protocol technique
Exclusions: 208/720 (29%) patients were excluded from the study during the single‐blind placebo run‐in period prior to randomization. The specific reasons for these exclusions were not given
Attrition: 109/512 (21%) patients withdrew from the study; the specific reasons were not given
WDAEs: 41/512 (8%) patients withdrew due to "a laboratory abnormality or adverse experience". This included 9 patients (or 14%) from the placebo group and a range of between 2% and 10% in each of the HCTZ 6.25 mg and HCTZ 25 mg treatment groups (actual % was not given). The specific reasons were not given. Note that the data above were pooled, not presented as separate for each treatment group |
| Selective reporting (reporting bias) |
High risk |
Baseline BP in each of the treatment groups was not reported (data were combined). Although the duration of the study was 12 weeks, the primary efficacy outcome (change from baseline in sitting DBP) was reported on at weeks 3 to 4 only. Reductions in DBP between 3 to 4 and 12 weeks were mentioned as being "similar" (no further information was given). All‐cause mortality and SAEs were not clearly documented. Total AEs were not reported; only AEs occurring in at least 2% of patients and either dose‐related or somehow related to active treatment were listed. Weight, heart rate, ECG, serum chemistry including glucose, lipids and calcium were measured but actual values were not reported on at endpoint |
| Industry sponsorship |
Unclear risk |
Sponsor not reported |
