Myers 2000.

Methods	Randomized, double‐blind, placebo‐controlled trial (parallel arms). Wash‐out = 4 weeks (single‐blind placebo run‐in). Multicenter; conducted in Europe and Canada
Participants	In Europe: supine DBP 95 to < 114 mmHg; in Canada: 95 to < 109 mmHg. Mean age 56 years. Males 54% Baseline supine (standing) BP was 161/101 (160/103) in the treatment group and 164/102 (166/104) in the control group
Interventions	Perindopril 2 mg, 4 mg or 8 mg/d + indapamide 0.625 mg, 1.25 mg or 2.5 mg/d (N = 317, all combined), indapamide 1.25 mg daily (N = 60) or placebo (N = 61) Trial duration = 8 weeks
Outcomes	Change from baseline in mean trough supine and standing DBP and SBP; 24‐hour ambulatory BP, response rate; heart rate; serum biochemistry
Notes	A sample size calculation was not provided. Markedly obese patients (BMI > 32) were excluded from the study. Patients received potassium supplementation if their serum potassium levels fell below 3.4 mmol/L. The study authors stated that there were no significant differences in the baseline patient characteristics across treatment groups. Total AEs not given
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	"...patients were randomly allocated to an 8‐week treatment period with either a perindopril/indapamide combination or placebo being administered using a double‐blind, parallel‐group study design." (line 9 under "Methods‐Patient population and inclusion criteria" p.318). "The study was a multinational, randomised, double‐blind comparison of perindopril and indapamide versus placebo using a seven‐way parallel‐group study design." (line 1 under "Study Design" p.318)
Allocation concealment (selection bias)	Unclear risk	Not stated by study authors
Blinding (performance bias and detection bias) All outcomes	Unclear risk	"...patients were randomly allocated to an 8‐week treatment period with either a perindopril/indapamide combination or placebo being administered using a double‐blind, parallel‐group study design." (line 9 under "Methods‐Patient population and inclusion criteria" p.318)
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Efficacy and safety analysis was based on an intention‐to‐treat technique with the last observation carried forward (LOCF) Exclusions: 58/496 (12%) of patients were excluded from the study during the placebo run‐in period prior to randomization. Specific reasons included: 12 patients for "patient choice", 19 ‐ supine DBP < 95 mmHg, 9 ‐ side effects, 6 ‐ supine DBP < 114 (Europe) or > 109 (Canada); 4 ‐ abnormal laboratory parameter, 3 ‐ investigator decision and 3 ‐ protocol violation. Note that 2 patients (i.e. their reasons for being excluded from the study) were not accounted for Attrition: 17/438 (3.9%) of patients withdrew from the study, 12 for adverse events, 4 for lack of efficacy and 1 for non‐medical reasons. The treatment groups from which these 17 patients withdrew were not mentioned WDAEs: 12/438 (2.7%) of patients withdrew due to AEs (dizziness, headache and nausea). The treatment groups from which these patients withdrew was not given
Selective reporting (reporting bias)	Low risk	Heart rate was measured, but not reported. Several serum biochemical levels, including sodium, uric acid, creatinine, glucose and cholesterol were reported in the results but not mentioned in the methods section. Variability in baseline patient characteristics and BP data was expressed in terms of standard error of the mean (SEM), rather than as standard deviation (SD). Mortalities: none. SAEs: 1 patient with myocardial infarction and 1 with angina reported as adverse events but that did not lead to death were mentioned, however there is no indication whether these patients were hospitalized or were forced to withdraw from the study. Total AEs: not reported. The incidence of 1 specific AE, cough, was reported (in the indapamide 1.25 mg group: 5%; in the placebo group: 0%)
Industry sponsorship	Unclear risk	Sponsor not reported