Riesen 2008.

Methods	Randomized controlled trial
Participants	The study location was Switzerland 527 participants were randomized to the intervention group and 601 participants were randomized to the control group The inclusion criteria were patients over 18 years attending primary care physician practices for treatment of primary hypercholesterolemia with a 10‐year CHD risk > 20%, CHD or other atherosclerotic disease, either statin naïve or on an accepted starting dose of lipid‐lowering medication, which had proved ineffective in reaching the target level of LDL‐C for that dose. Statin‐naïve patients (with an LDL‐C > 3.5 mmol/L fasting level) were required to complete dietary counseling before entering the study. Patients who switched from accepted starting doses of other lipid‐lowering medication (with an LDL‐C > 3.1 mmol/L fasting level) were directly enrolled in the study. Another inclusion criterion was a fasting triglyceride (TG) level of 94.52 mmol/L The exclusion criteria were heterozygous or homozygous familial hypercholesterolemia, type III hyperlipoproteinemia (familial dysbetalipoproteinemia), or secondary hypercholesterolemia; hypersensitivity reactions or serious adverse effects (e.g. myopathy) in relation to other statins were also excluded, pregnant or breastfeeding women; women of childbearing potential were asked to use adequate contraception during the study; unstable cardiovascular disease, uncontrolled diabetes, active liver disease, renal impairment as defined by a serum creatinine level > 220 mmol/L, any medical condition requiring cyclosporine therapy, and a history of alcohol and/or drug abuse
Interventions	Intervention: 10 MG PLUS Patients received a daily oral treatment with rosuvastatin and access to compliance enhancement tools (10 mg Plus group) for 24 weeks. Patients were assessed at week 4 and at week 12 to review fasting levels of TC, LDL‐C, HDL‐C, and triglycerides. For patients not achieving the 1998 European target for LDL‐C at week 12, the daily dose of rosuvastatin was increased to 20 mg for the remainder of the study. Patients in the 10 mg Plus group received a starter pack containing a videotape and educational leaflets concerning their condition. These patients also received newsletters at regular intervals and had access to both a telephone helpline and an Internet website, all designed to reinforce the initial message in the starter pack Control: 10 MG Patients received a daily oral treatment with rosuvastatin alone (10 mg group) for 24 weeks. Patients were assessed at week 4 and at week 12 to review fasting levels of TC, LDL‐C, HDL‐C, and triglycerides. For patients not achieving the 1998 European target for LDL‐C at week 12 the daily dose of rosuvastatin was increased to 20 mg for the remainder of the study
Outcomes	The measures of adherence was the difference between dispensed and returned tablets in comparison with the number of days between visits. Patients were asked to return unused medication to the study investigator at week 12 and week 24. The patient outcomes were the number and percentage of patients in both treatment groups who reached the 1998 European goal for LDL‐C (< 3.0 mmol/L) after 24 weeks of therapy; the number and percentage of patients within the 1998 European goal for LDL‐C at week 12, the number and percentage of patients within the 1998 European goal for TC (< 5.0 mmol/l) at week 12 and week 24, and the number and percentage of patients within the 2003 European goal for LDL‐C (< 2.5 mmol/L) and for TC (< 4.5 mmol/L) at week 12 and week 24. Other secondary efficacy endpoints were the number of patients with a dose increase to 20 mg rosuvastatin at week 12; and the percentage change in LDL‐C, TC, HDL‐C, and TG between baseline and week 24
Notes	Non‐compliant with blood test have been excluded, so that adherence even without intervention is very high 97%
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Randomization was not described in detail. "This was a cluster‐randomised, multicentre, open label, parallel group study of 24 weeks' duration and conducted throughout Switzerland. A cluster randomisation procedure was used and all patients in each centre were assigned to the same treatment group." (pg 421)
Allocation concealment (selection bias)	Unclear risk	No information was provided about how allocation was handled
Selective reporting (reporting bias)	Unclear risk	No protocol available; although it appears that everything was reported it is difficult to determine this without a protocol
Other bias	Low risk	The study seems to be free of other types of bias
Blinding of outcome assessment (detection bias) Adherence measure	Unclear risk	(PRIMARY) PILL COUNT ‐ Patients were asked to return all unused rosuvastatin tablets and containers to the investigator at week 12 and week 24. The patient's compliance was determined by the difference between the dispensed and the returned tablets in comparison with the number of days between the visits. No mention of blinding the outcome assessors
Blinding of outcome assessment (detection bias) Patient outcome	Low risk	(PRIMARY) BLOOD TESTS ‐ This is an objective measure of outcome
Blinding of participants (performance bias) Adherence measure	Unclear risk	(PRIMARY) PILL COUNT ‐ The results may have been reliable if it was conducted in an unannounced manner. If participants knew that their pill were being counted, then they could take away some drugs before returning the containers. Insufficient information about the how much participants knew about this outcome measure
Blinding of participants (performance bias) Patient outcome	Low risk	(PRIMARY) BLOOD TESTS ‐ This is an objective measure of outcome
Blinding of personnel (performance bias) Adherence measure	Unclear risk	(PRIMARY) PILL COUNT ‐ No information on blinding given. There is insufficient information to permit judgment of 'Low risk' or 'High risk'
Blinding of personnel (performance bias) Patient outcome	Low risk	(PRIMARY) BLOOD TESTS ‐ This is an objective measure of outcome
Incomplete outcome data (attrition bias) Adherence measure	Unclear risk	(PRIMARY) PILL COUNT ‐ information in the study about missing data is too confusing to make a judgment. There are different numbers in different parts of the paper, and it is unclear just how many missing data there are
Incomplete outcome data (attrition bias) Patient outcome	Unclear risk	(PRIMARY) BLOOD TESTS ‐ it is unclear just how many missing data there are