Cerebral small vessel disease or intracranial large vessel atherosclerosis may carry different risk for future strokes

Background The effect of cerebral small vessel disease(CSVD)and intracranial arterial stenosis(ICAS)on stroke outcomes remains unclear.Methods Data of 1045 patients with minor stroke or transient ischaemic attack(TIA)were obtained from 45 sites of the Clopidogrel in High-Risk Patients with Acute Non-disabling Cerebrovascular Events(CHANCE)trial.We assessed the associations of burdens of CSVD and ICAS with new strokes and bleeding events using multivariate Cox regression models and those with modified Rankin Scale(mRS)scores using ordinal logistic regression models.Results Among the 1045 patients,CSVD was present in 830 cases(79.4%)and ICAS in 460(44.0%).Patients with>1 ICAS segment showed the highest risk of new strokes(HR 2.03,95%CI 1.15 to 3.56,p=0.01).No association between CSVD and the occurrence of new strokes was found.The presence of severe CSVD(common OR(cOR)2.01,95%CI 1.40 to 2.89,p<0.001)and>1 ICAS segment(cOR 2.15,95%CI 1.57 to 2.93,p<0.001)was associated with higher mRS scores.Severe CSVD(HR 10.70,95%CI 1.16 to 99.04,p=0.04),but not ICAS,was associated with a higher risk of bleeding events.Six-point modified CSVD score improved the predictive power for bleeding events and disability.Interpretation CSVD is associated with more disability and bleeding events,and ICAS is associated with an increased risk of stroke and disability in patients with minor stroke and TIA at 3 months.CSVD and ICAS may represent different vascular pathologies and play distinct roles in stroke outcomes.

Rationale and design of a randomised double-blind 2×2 factorial trial comparing the effect of a 3-month intensive statin and antiplatelet therapy for patients with acute mild ischaemic stroke or high-risk TIA with intracranial or extracranial atherosclerosis(INSPIRES)

Background It remains unclear if intensive antiplatelet and statin treatments begun within 24-72 hours of cerebral ischaemic events from intracranial or extracranial atherosclerosis is effective or safe.Methods The Intensive Statin and Antiplatelet Therapy for High-risk Intracranial or Extracranial Atherosclerosis(INSPIRES)trial is a randomised,double-blind,placebo-controlled,multicentre and 2×2 factorial trial.6100 individuals between the ages of 35 and 80 who have experienced a mild ischaemic stroke or high-risk transient ischaemic attack(TIA)within the previous 72 hours that is attributed to≥50%atherosclerotic stenosis of a major intracranial or extracranial artery or multiple infarctions of atherosclerotic origin will be enrolled in the trial.Eligible subjects will be randomised 1:1:1:1 to one of four groups:(1)intensive antiplatelet therapy(combined clopidogrel and aspirin for days 1-21,then aspirin placebo and clopidogrel for days 22-90)plus immediate intensive statin therapy(atorvastatin at a dose of 80 mg daily for the first 21 days,then 40 mg daily for days 22-90);(2)intensive antiplatelet therapy plus delayed intensive statin therapy(atorvastatin placebo for days 1-3,followed by 40 mg per day of atorvastatin for days 4-90);(3)standard antiplatelet therapy(combination of clopidogrel placebo with aspirin for 90 days)plus immediate intensive statin therapy and(4)standard antiplatelet therapy plus delayed intensive statin therapy.The primary efficacy endpoint is any new stroke(ischaemic or haemorrhagic)within 90 days after randomisation.The primary safety endpoint is moderate to severe bleeding at 90 days.Conclusion The INSPIRES trial will assess the efficacy and safety of intensive antiplatelet therapy and immediate intensive statin therapy begun within 72 hours of onset in decreasing the recurrent stroke at 90 days in patients with acute mild ischaemic stroke or high-risk TIA of intracranial or extracranial atherosclerosis origin.