Krantz 1988.
| Methods | Randomized, double‐blind, placebo‐controlled trial (parallel arms). Wash‐out period = 6 weeks. Conducted in USA | |
| Participants | DBP 90 to 108 mmHg. Mean age 45.2 years. All patients were male. Baseline BP was 138.2/89 mmHg in the treatment group and 136.3/86.8 mmHg in the placebo group | |
| Interventions | Atenolol 25 mg bid (N = 12), propranolol 40 mg bid (N = 12), HCTZ 25 mg bid (N = 10) or placebo (N = 12). After 2 weeks on atenolol, propranolol or HCTZ non‐responsive patients had their dosages doubled. All patients were determined to either have not achieved BP response and/or exceeded exercise‐induced increases in heart rate, therefore, this review will compare the HCTZ 50 mg bid dosage versus placebo Treatment duration = 2 weeks (low‐dose) + 4 weeks (high‐dose) | |
| Outcomes | Sitting (resting) DBP and SBP measured at 4 weeks; heart rate, ECG; psychological and behavioral testing | |
| Notes | A sample size calculation was not provided. Dosage of HCTZ was doubled from 25 to 50 mg bid for all patients receiving HCTZ after 2 weeks of treatment. Study authors did not report whether there were statistically significant differences in baseline patient demographics and characteristics across treatment groups. Resting BP measurements were taken while patient was sitting. Baseline BP was not given. Peak or trough BP not mentioned. WDAEs, mortalities, SAEs and total AEs were not reported. Biochemical data not given | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | "In a double‐blind study, mild hypertensive's were assigned randomly to receive either propranolol, atenolol, placebo, or a diuretic (hydrochlorothiazide) for 6 weeks." (line 1 under "Methods‐Overview" p.617). No further information was given |
| Allocation concealment (selection bias) | Unclear risk | Not stated by study authors |
| Blinding (performance bias and detection bias) All outcomes | High risk | "In a double‐blind study, mild hypertensive's were assigned randomly to receive either propranolol, atenolol, placebo, or a diuretic (hydrochlorothiazide) for 6 weeks." (line 1 under "Methods‐Overview" p.617) "...subjects were randomised into one of four treatments following double‐blind procedures." (line 6 from top of p.617). "...only the treating physician (JDL or EF), who did not conduct any of the behavioural or psychophysiological testing, was aware of individual patients' drug assignments." (line 8 from top of p.617) This did not imply that the treating physician did not perform BP readings and, therefore, had knowledge of which patients may be receiving treatment as opposed to a placebo pill "Initial drug dosages were 25 mg b.i.d. for hydrochlorothiazide and for atenolol and 40 mg b.i.d. for propranolol, taken in visually identical white capsules." (line 14 from top of p.617). After the second week of treatment, drug dosages were doubled for all patients, but it is not known if the placebo group also received 2 times as many capsules |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | It was not stated whether efficacy analysis was based on an intention‐to‐treat (ITT) or per‐protocol technique Exclusions: the number of patients excluded from the study during the drug wash‐out period prior to randomization was not given Attrition: 5 patients withdrew from the study for the following reasons: 1 ‐ "untoward side effects", 4 ‐ "errors in conducting the protocol" or "life events requiring withdrawal". Although the study authors stated that the patients were about equally distributed between treatment groups, the actual number of dropouts between groups was not reported WDAEs: not given |
| Selective reporting (reporting bias) | High risk | Except for mean age, baseline patient demographics and characteristics were not documented. Variability was not included in the mean age of patients at baseline. Biochemical including hematology, serum chemistry and urinalysis data were not reported in the study. Psychological and symptom questionnaires were conducted during the study, but their results were not reported. Mortalities, SAEs and total AEs were not reported |
| Industry sponsorship | Low risk | Supported by NIH grant HL31514 and USUHS protocol R07233 |