HAPPHY 1987.
| Study characteristics | ||
| Methods | Randomized, open‐label trial | |
| Participants | 6569 male patients from 15 countries in Europe and North America aged 40 to 64 with hypertension (DBP 100 to 130 mmHg) Mean age 52 years |
|
| Interventions | Bendroflumethiazide 5 mg daily or hydrochlorothiazide 50 mg daily Atenolol 100 mg daily or metoprolol 200 mg daily |
|
| Outcomes | Serum potassium, creatinine, cholesterol, urate Mortality (cause‐specific) Non‐fatal MI Non‐fatal stroke AEs BP at 1 year Duration: mean follow‐up 3.8 years |
|
| Notes | — | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "Patients were randomised to open treatment with a diuretic or a beta‐blocker, after stratification into nine groups according to predicted CHD risk based upon age, serum cholesterol, smoking habits and SBP... Individual centres could choose to use either atenolol or metoprolol and bendrofluazide or hyrochlorothiazide. The fact that there was no randomisation between centres choosing different alternatives, militated against a valid comparison of the two beta‐blockers or of the two diuretics used in the trial." No further information provided regarding the method of randomization. |
| Allocation concealment (selection bias) | Unclear risk | No description of allocation concealment was provided. |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Quote: "Patients were randomised to open treatment." |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | Quote: "An independent end‐point committee reviewed the diagnoses of the end‐points without knowing to which treatment patients had been randomised." Criteria for endpoints were well defined in the methods. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Quote: "the crude withdrawal rate, calculated as the number of withdrawn patients divided by the total number of patients, was 8.9 and 7.9% in the diuretic and beta‐blocker groups, respectively (NS), corresponding to an annual withdrawal rate of 2.4% per year for the diuretic treated group and 2.1 % for the beta‐blocker treated group." Reasons for patient withdrawal are itemized and appear similar. Quote: "The analyses were made on an 'intention‐to‐treat' basis." |
| Selective reporting (reporting bias) | Unclear risk | Methods are well documented, but without a protocol, cannot fully determine if all prespecified outcomes have been reported. |
| Use of supplemental drugs | High risk | Additional treatment was consistent across first four steps, but was then free of choice in this non‐blinded trial.
Step 1: hydralazine (75 mg)
Step 2: hydralazine (150 mg)
Step 3: step 2 + spironolactone (75 mg)
Step 4: step 2 + spironolactone (150 mg)
Step 5: step 4 + optional drug Quote: "If the goal BP was not attained with the drugs and doses shown in the schedule, other drugs, free of choice, were added." |
| Industry sponsorship | High risk | Quote: "The trial was supported economically by AB Hassle, Mcilndal, a subsidiary of AB ASTRA, Sweden and ICI, Macclesfield, UK." |