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.

Chinese Stroke Association guidelines for clinical management of cerebrovascular disorders:executive summary and 2019 update of the management of high-risk population

Aim Cerebrovascular disease is the leading cause of death and disability in China,causing a huge burden among patients and their families.Hence,stroke prevention is critical,especially in the high-risk population.Here,we present the evidence-based guideline suitable for the Chinese population.Methods Literature search of PubMed and Cochrane library(from January 1964 to June 2019)was done.After thorough discussion among the writing group members,recommendations were listed and summarised.This guideline was reviewed and discussed by the fellow writing committees of the Chinese Stroke Association’s Stroke.Results This evidence-based guideline was written in three parts:controlling the risk factors of stroke,utilisation of antiplatelet agents and assessing the risks of first-ever stroke.All recommendations were listed along with the recommending classes and levels of evidence.Conclusions This guideline provides recommendations for primary prevention of cerebrovascular disease among high-risk population in China.Controlling related risk factors,appropriately using antiplatelet agents,assessing the risk of developing first-ever stroke should help reduce the rate of cerebrovascular disease in China.