Brown 1997.

Study characteristics
Methods	Cross‐over randomised controlled clinical trial Randomisation ratio: 1:1 Equivalence design: 2‐sided confidence interval Open‐label
Participants	N recruited = 31 N randomised = 31 (cross‐over ‐ both groups received intervention) N reported outcomes = 29 Mean age 49 ± 7 yrs INCLUSION CRITERIA "All were men less than or equal to 65 years old at high risk for future cardiac events by virtue of: (1) an elevated apoprotein B greater than or equal to 125mg/dl, (2) at least 1 coronary lesion greater than or equal to 50% stenosis or 2 lesions greater than or equal to 30% stenosis, as documented in the baseline angiogram, and (3) a family history of premature cardiovascular events. All patients signed an approved written consent form." EXCLUSION CRITERIA Not reported COUNTRY/SETTING: USA STUDY PERIOD: Not reported
Interventions	Number of study centres: 1 "All patients received the 3‐drug regimen listed above (niacin, lovastatin 20mg BD, colestipol 10g BD), using regular niacin, for 12 months, with dosage adjustment to a target cholesterol of 150 to 175 mg/dl, and to minimize side effects." INTERVENTION (2) AND CONTROL (1) GROUP at 12 months: "At 12 months, patients were randomly assigned to: (1) continue with regular niacin at a dosage identical to that established in the 12 month dose‐finding period, or (2) change to polygel controlled‐release niacin at that daily dosage, but given twice rather than 4 times/day." INTERVENTION AND CONTROL GROUP at 20 months: "At 20 months, groups (1) and (2) were reversed (crossover)." "This regimen continued for 8 more months. Just before the clinic visit at 28 months, patients completed a mail‐in questionnaire comparing the 2 niacin preparations in terms of a variety of possible side effects and specifying which of the 2 preparations they preferred. After 30 months, all these drugs were discontinued and a postdrug follow‐up evaluation was performed 6 weeks later."
Outcomes	TIME OF OUTCOME MEASUREMENTS "Plasma very low‐density lipoprotein (VLDL), LDL, and HDL cholesterol and triglycerides, apolipoprotein B, and aspartate aminotransferase were measured at baseline and every 4 months at the Northwest Lipid Research Laboratory. At entry (before treatment), at 6 months, 12 months, 20 months, 28 months, and 6 weeks after stopping the triple‐drug regimen, the lipid and clinical laboratory determinations listed in Table II were obtained. HDL2 and HDL3 cholesterol were measured at baseline, at 1 and 2 years, and at 6 weeks after discontinuing therapy." PRIMARY OUTCOME: lipid levels SECONDARY OUTCOMES: compliance, side effects
Notes	Commercial funding/non‐commercial funding/other funding: "The pharmaceutical supplies were provided by Merck Research Laboratories, Inc., West Point, Pennsylvania; Upjohn Co., Inc., and Upsher‐Smith Inc., Minneapolis, Minnesota. This study was supported in part by grants from the National Heart, Lung, and Blood Institute and National Institutes of Health, Bethesda, Maryland; in part by the University of Washington Clinical Research Center (NIH #RR31), Seattle, Washington; and in part by a grant from the John L. Locke, Jr. Charitable Trust, Seattle, Washington." Stated aim for study: "To identify a regimen that is effective among such hyperlipidemic coronary disease patients (usually meets </‐100 mg/dl target), is well tolerated, and is realistic, we have employed and evaluated a 3‐drug combination with niacin, lovastatin, and colestipol, in moderate doses in such patients. Furthermore, we have objectively compared a polygel controlled‐release niacin (Upsher‐Smith, Minneapolis) with regular niacin used in this regimen in a randomized, crossover trial design."
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not reported
Allocation concealment (selection bias)	Unclear risk	Not reported
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Unblinded open‐label study
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	"2 left the study during the 12‐month run‐in phase due to time conflict"
Selective reporting (reporting bias)	Low risk	All outcomes reported