Table 1.

Protocol amendments and other changes to trial practice

Criterion	Previous versions	Current version/status	Reason
Protocol changes
Posterior circulation stroke (POCS)	Excluded	Included	To expand the inclusion criteria; posterior circulation stroke can lead to cognitive decline
Exclusion of NYHA 3 or 4	Exclusion criterion	Removed	To simplify protocol
LDL-c target	< 2.0 mmol/l	< 1.4 mmol/l	Half of patients already at LDL-c < 2 at baseline
Total cholesterol	< 4.0 mmol	< 3.1 mmol/l	Ditto
Glucose monitoring		Glucose, HbA1C	Some BP and lipid drugs may reduce, or cause, diabetes mellitus
Quality of life	DEMQOL	Removed	To simplify protocol
Screening	As telephone call	As research clinic visit	To reduce recruitment of ineligible patients
Time from screening to randomisation	2 weeks	1 week	To accelerate recruitment
Guideline statin dosage	Simvastatin 40 mg, pravastatin 40 mg, fluvastatin 40 mg	Simvastatin 10 to 40 mg, pravastatin 10 to 40 mg, fluvastatin 10 to 80 mg	To reflect NICE guidelines on lipid management (CG 67, 2008)
Statin classification	Guideline statin:	Guideline statin:	To clarify intensive versus guideline lipid lowering management
	simvastatin < 40 mg, pravastatin any dose, fluvastatin any dose, atorvastatin 10 mg.	simvastatin ≤ 40 mg, pravastatin any dose, fluvastatin any dose, atorvastatin ≤ 20 mg.
	Intensive statin: atorvastatin ≤ 40 mg	Intensive statin: atorvastatin > 20 mg, rosuvastatin any dose
Trial duration and participant involvement	8 years	4 years	To shorten trial since the main phase is no longer justified
BP and lipid management in follow-up visits		‘Floating’ visit at any time outside the planned visits at 3, 6, 12, 18, 24, 30, 36 and 42 months	To allow enhanced escalation of treatment, as appropriate
Baseline and follow-up BP and HR monitoring	Three measurements in rapid succession	Four measurements in rapid succession including one standing	To detect postural hypotension
Neuroimaging sub-study scan		CT scan on treatment (plus collection of any clinical scans during treatment)	To detect potential affects on atrophy, white matter changes
Follow-up visits	Seen in clinic once a year with interval blinded telephone follow-up.	Seen in clinic once every 6 months	To assess latest BP and/or lipid levels and escalate treatment as appropriate
Other changes
Minimisation variables	As in section Minimisation (on key prognostic/logistical variables) above	Age, systolic BP, LDL-c	Small trial size precluded numerous minimisation variables
Email reminders		Twice yearly to investigators.	To highlight the need to achieve targets in BP and lipid lowering in patients randomised to intensive management