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. 2016 Nov 26;2016(11):CD009462. doi: 10.1002/14651858.CD009462.pub2

Saito 1991.

Methods Study design: double‐blind placebo controlled study
 Setting/location: not reported. Country: not reported
 Period of study: not reported (published in 1991)
 Unit of randomisation: participant
 Unit of analysis: participant
Trial test: not reported
Analysis strategy: not reported
Participants Inclusion criteria:

  • Participants diagnosed as having hyperlipidaemia (including participants with familiar hypercholesterolaemia)

  • Age range: 18‐65 years


Exclusion criteria:

  • Liver disease

  • Serious renal disease

  • Recent myocardial infarction or apoplexy

  • Heart failure

  • Secondary hyperlipidaemia

  • Hypersensitive to drugs

  • Pregnant

  • Breast feeding


Randomised: 172 participants (not reported by arm)
Participants assessed at 0 weeks: 147 participants (M‐DG1: n = 29, E‐DG1: n = 27, M‐DG2: n = 32, E‐DG2: n = 28, PG: n=31)
Withdrawals (subject decision): 46 participants (M‐DG1: n = 7, E‐DG1: n = 10, M‐DG2: n = 10, E‐DG2: n = 10, PG: n=9)
Participants assessed at + 4 weeks: 101 participants (M‐DG1: n = 22, E‐DG1: n = 17, M‐DG2: n = 22, E‐DG2: n = 18, PG: n = 22)
Definition of hyperlipidaemia: a serum cholesterol value of at least 220 mg/dL at each determination. The serum cholesterol was determined at least twice at intervals of 2‐4 weeks
Baseline characteristics:
Total cholesterol (TC) (mg/dL) (mean (SD)): (M‐DG1: 273.0 (39.6), E‐DG1: 274.9 (37.2), M‐DG2: 277.4 (49.8), E‐DG2: 288.8 (46.9), PG: 285.8 (44.6))
LDL‐C (mg/dL) (mean (SD)): (M‐DG1: 182.7 (46.8), E‐DG1: 195.9 (36.7), M‐DG2: 194.2 (48.1), E‐DG2: 204.3 (52.2), PG: 200.2 (54.3))
HDL‐C (mg/dL) (mean (SD)): (M‐DG1: 54.4 (24.3), E‐DG1: 47 (15), M‐DG2: 52.7 (17.9), E‐DG2: 53.2 (13), PG: 49.9 (14.3))
Triglycerides (mg/dL) (mean (SD)): (M‐DG1: 179.6 (105.3), E‐DG1: 160.3 (72.3), M‐DG2: 152.5 (77.4), E‐DG2: 156.3 (68.9), PG: 178.4 (124.5))
Interventions Type of interventions: morning vs evening doses of simvastatin (figure 1 trial report)
 M‐DG1: 2.5 mg daily dose of simvastatin with a placebo tablet of simvastatin 5 mg tablet in the morning and a placebo tablet of simvastatin 2.5 mg with a placebo tablet of simvastatin 5 mg in the evening
 E‐DG1: a placebo tablet of simvastatin 2.5 mg with a placebo tablet of simvastatin 5 mg in the morning and 2.5 mg daily dose of simvastatin with a placebo tablet of simvastatin 5 mg in the evening
 M‐DG2: 5 mg daily dose of simvastatin with a placebo tablet of simvastatin 2.5 mg in the morning and a placebo tablet of simvastatin 2.5 mg with a placebo tablet of simvastatin 5 mg in the evening
 E‐DG2: a placebo tablet of simvastatin 5 mg with a placebo tablet of simvastatin 2.5 mg in the morning and 5 mg daily dose of simvastatin with a placebo tablet of simvastatin 2.5 mg tablet in the evening
PG: a placebo tablet of simvastatin 2.5 mg with a placebo tablet of simvastatin 5 mg in the morning and in the evening
Duration of intervention: 20 weeks including:

  • preliminary observation study: 4 weeks (placebo);

  • treatment period: 12 weeks (experimental drugs);

  • follow‐up observation period: 4 weeks (placebo).


During the experimental period, the participants were instructed not to change their eating habits and alcohol consumption was prohibited on the day before test were performed. Concomitant administration of drugs known to affect serum lipid levels was prohibited
Outcomes Lipid levels: TC, LDL‐C, HDL‐C, apolipoproteins and triglycerides levels (mg/dL)
Adverse events
Notes  
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk No information provided
Allocation concealment (selection bias) Unclear risk Quote: "was placed in envelopes for allocation to the subjects" (page 817 trial report)
Comment: did not report if the assignment envelopes were used with appropriate safeguards (e.g. if envelopes were unsealed or non‐opaque or not sequentially numbered)
Blinding of participants and personnel (performance bias) 
 All outcomes Low risk Quote: "To preserve the double‐blind nature of this study, the double‐dummy method was applied" (page 817 trial report)
Blinding of outcome assessment (detection bias) 
 All outcomes Low risk The determination of serum lipid parameters was realized in a central laboratory
Incomplete outcome data (attrition bias) 
 All outcomes High risk The authors did not report adequately the number and sources of withdrawals by arm (total: 46/172; 26.7%)
Selective reporting (reporting bias) Unclear risk Insufficient information to permit judgement of ‘low risk’ or ‘high risk’
Other bias Unclear risk Insufficient information to assess whether an important risk of bias existed