1. SPARCL – Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Jim McMorran Coventry GP GP with Specialist Interest in Diabetes and Cardiovascular Risk Coventry PCT

2. Evidence Base Prior to SPARCL Primary Prevention of Stroke –1mmol/l reduction in LDL > 21% reduction in stroke risk Lipid lowering post cerebrovascular disease –HPS no reduction in the risk of stroke –HPS showed reduction in risk of myocardial infarctions

3. SPARCL Double blind randomised – placebo or atorvastatin 80mg Patients with a history of stroke or TIA 1-6 months prior to study entry (4731) LDL 2.9 -4.9 mmol/L (3.3 mmol/L) Exclusions – AF, other cardiac sources of embolism, SAH Primary end point first fatal or nonfatal stroke Median follow-up 4.9 years

4. SPARCL Results Mean LDL -> atorvastatin 1.9 mmol/l; placebo 3.3 mmol/l Primary endpoint fatal or nonfatal stroke –311 (13.1%) placebo group –265 (11.2%) treatment group (5 year reduction 2.2%) –Hazard ratio 0.84 (0.71-0.99) Different strokes –Atorvastatin group – 218 ischaemic strokes, 55 haemorrhagic strokes –Placebo – 274 ischaemic strokes, 33 haemorrhagic strokes –492 >=1 ischaemic stroke, 88 >= 1 haemorrhagic stroke Reduction in risk of major CV events 3.5% for statin group Mortality was similar in both groups

5. SPARCL – adverse events No significant difference in incidence of adverse events Persistent raised ALT > x3 normal more frequent in atorvastatin group –2.2% versus 0.5% Rhabdomyolysis –2 cases in statin group, 3 in placebo group Haemorrhagic stroke –increase in statin group (relative risk increased by 66%) –HPS – patients with cerebrovascular disease increased haemorrhagic stroke –Potential risk of recurrent haemorrhage should be considered in patient with hx of haemorrhagic stroke

6. SPARCL Results NNT –46 patients required to be treated for 5 years in order to prevent one stroke (24-243) –29 patients required to be treated for 5 years in order to prevent one major cardiovascular event (18-75) –32 patients required to be treated for 5 years in order to prevent one revascularization procedure (22-59)

7. Talking points Why did SPARCL show reduction in recurrent stroke whereas HPS did not? –? Related to respective reductions in LDL (1.4 mmol/L SPARCL, 1 mmol/L HPS) –HPS enrolled on average 4.3 years after stroke Could factors such of heterogeneity of patients (cause of stroke, vascular risk) and low rate of primary outcome be influencing significance of results? stroke and lipids section - General Practice Notebook

8. SPARCL - Conclusions Evidence for prevention of recurrent strokes (16% relative reduction) LDL in treatment group reduced to 1.9 mmol/l (JBS2) Evidence for reduction in major cardiovascular events (20% relative reduction) Ischaemic stroke as CHD risk equivalent