Nieuwkerk 2012.

Methods	Randomized controlled trial
Participants	The study location was Academic Medical Center and Slotervaart Hospital Amsterdam, The Netherlands 101 participants were randomized to the intervention group and 100 participants were randomized to the control group The inclusion criteria were patients (aged > 18 years) with indications for statin use The exclusion criteria were severe fasting dyslipidemia (total cholesterol > 9.0 mmol/L or triglycerides > 4.0 mmol/L), fasting glucose > 7.0 mmol/L. Patients who had used statins for > 3 months before inclusion, who had histories of drug and/or alcohol abuse, who were pregnant or breast‐feeding, or who had life expectancies < 2 years
Interventions	Intervention: EXTENDED CARE Subjects in extended care (EC) received multifactorial risk‐factor counseling, in addition to routine care (RC). During the counseling the nurse practitioner explained the presence of unmodifiable risk factors, such as age, gender, and family history, and modifiable risk factors, such as lipid levels, diabetes mellitus, blood pressure, overweight, smoking habits, and physical activity. The study nurse was not blinded to the purpose of the study. The counseling focused on changing modifiable risk factors such as increasing medication adherence, reducing overweight, smoking cessation, and increasing physical activity. All obtained data were summarized in a personal risk‐factor passport: a graphical presentation of the patient's calculated 10‐year cardiovascular disease risk. It also showed the target risk that could be reached if all the patient's modifiable risk factors were optimally treated, as well as the standard age‐ and gender‐related risk. 10‐year risk and target risk were calculated using the Framingham risk score. The risk‐factor passport contained the most recent ultrasound image of the patient's carotid artery, as well as an example of a healthy and an unfavorable image of the carotid artery, which were both explained and discussed by the nurse practitioner. This risk‐factor passport was updated during each follow‐up visit Control: ROUTINE CARE Routine care consisted of measuring body weight and blood pressure and performing a capillary lipid profile at each visit. Initially, all participants received atorvastatin 10 mg, unless baseline cholesterol levels were severe and more aggressive therapy was needed. Dose escalation during the study period was allowed if deemed appropriate by the treating physician
Outcomes	The measures of adherence were 2 validated self report questions. First question asked subjects how many days during the past week they took their lipid‐lowering medications on a 5‐point scale (1 = not 1 day, 5 = all 7 days). In the second question, subjects were asked what percentage of their prescribed lipid‐lowering medications they took during the past month (1 = < 30%, 9 = 100%). Patients were followed‐up at 3, 9, and 18 months The patient outcomes were lipid levels and anxiety. A fasting lipid profile was analyzed from capillary finger‐stick whole blood using the Cholestech LDX Lipid Analyzer, which measures total cholesterol, triglycerides, and high‐density lipoprotein cholesterol. Low‐density lipoprotein (LDL) cholesterol was calculated. Anxiety was assessed using the Hospital Anxiety and Depression Scale. Higher scores indicate higher levels of anxiety. Quality of life (QoL) was measured using the Medical Outcomes Study Short‐Form 12‐Item Health Survey. 2 subscale scores can be obtained, a physical health score and a mental health score. Higher scores indicate better physical and mental health. Symptoms related to the use of lipid‐lowering medication were assessed using a symptom checklist containing 20 items that were derived from the item bank of the European Organisation for Research and Treatment of Cancer QoL group. The checklist includes the most frequently occurring side effects observed by statin users. The presence of a symptom during the past 4 weeks was scored on a 4‐point scale. A summary score was calculated. The self reported questionnaires were completed at baseline and then before subsequent consultations. Carotid IMT and FMD were measured at baseline and at month 18. B‐mode ultrasound IMT measurements were performed in the far walls of the carotid arteries. The mean of 3 measurements was used to calculate IMT. FMD was determined in terms of the percentage change in diameter relative to the baseline measurement. Baseline vessel diameter was calculated as the average of the 3 baseline measurements. Each of the imaging operations was performed by a single highly skilled sonographer
Notes	―
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer program was used for randomization. "After inclusion, patients were randomly assigned to RC or extended care (EC), using a randomization computer program, to obtain an equal distribution of primary and secondary prevention patients, hospital origin, and gender in the 2 groups." (pg 666)
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	High risk	(PRIMARY) SELF REPORT ‐ QUESTIONNAIRE ‐ The study nurse was not blinded to the purpose of the study (pg 668)
Blinding of outcome assessment (detection bias) Patient outcome	Low risk	(PRIMARY) FASTING LIPID LEVEL ‐ Although the study nurse was not blinded to the purpose of the study (pg 668), this is an objective measure
Blinding of outcome assessment (detection bias) Patient outcome	High risk	(PRIMARY) ANXIETY (HAS SCORE) ‐ The study nurse was not blinded to the purpose of the study; this is a subjective measure
Blinding of participants (performance bias) Adherence measure	High risk	(PRIMARY) SELF REPORT ‐ QUESTIONNAIRE ‐ The author notes that patients were not blinded to the study. They were aware that enhancing adherence was a study aim. They were informed that responses to questions about adherence were handled confidential and anonymously making use of code numbers, and that their responses were not communicated to their treating physician
Blinding of participants (performance bias) Patient outcome	High risk	(PRIMARY) ANXIETY (HAS SCORE) ‐ The author notes that patients were not blinded to the study. They were aware that enhancing adherence was a study aim. They were informed that responses to questions about adherence were handled confidential and anonymously making use of code numbers, and that their responses were not communicated to their treating physician; this is a subjective measure
Blinding of participants (performance bias) Patient outcome	Low risk	(PRIMARY) FASTING LIPID LEVEL ‐ This is an objective measure of outcome
Blinding of personnel (performance bias) Adherence measure	Unclear risk	(PRIMARY) SELF REPORT ‐ QUESTIONNAIRE ‐ 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	Unclear risk	(PRIMARY) ANXIETY (HAS SCORE) ‐ 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) FASTING LIPID LEVEL ‐ This is an objective measure of outcome
Incomplete outcome data (attrition bias) Adherence measure	Unclear risk	(PRIMARY) SELF REPORT ‐ QUESTIONNAIRE ‐ Attrition rates are not balanced
Incomplete outcome data (attrition bias) Patient outcome	Unclear risk	(PRIMARY) FASTING LIPID LEVEL ‐ Attrition rates were not balanced
Incomplete outcome data (attrition bias) Patient outcome	Unclear risk	(PRIMARY) ANXIETY (HAS SCORE) ‐ Attrition rates were not balanced