Antiplatelet Therapy in Cerebral Small Vessel Disease
- 317 Downloads
Purpose of Review
We critically evaluate the evidence for the use of antiplatelet therapy for stroke prevention following lacunar stroke and in patients with hemorrhage-prone cerebral small vessel disease.
Pooled lacunar stroke subgroup analyses of all relevant randomized controlled trials to date suggest a 22% relative risk reduction in recurrent stroke by single antiplatelet therapy (RR 0.77, 95% CI 0.62–0.97) compared with placebo, no consistent suggestion of variable efficacy amongst specific antiplatelet agents, and the absence of clear benefit with dual over single antiplatelet therapy. Current data does not support withholding antiplatelet therapy where otherwise indicated in patients with cerebral microbleeds on MRI or those who have suffered intracerebral hemorrhage.
Antiplatelet monotherapy appears to provide persistent secondary stroke prevention in patients with lacunar stroke. Whether phosphodiesterase inhibitors, particularly cilostazol, provide additional advantage in patients with cerebral small vessel disease is worthy of further investigation.
KeywordsLacunar stroke Antiplatelet Antithrombotic Cerebral small vessel disease Microbleed Intracerebral hemorrhage
Compliance with Ethical Standards
Conflict of Interest
Danielle de sa Bouasquevisque, Oscar R. Benavente, and Ashkan Shoamanesh each declare no potential conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 1.Gorelick PB, Scuteri A, Black SE, Decarli C, Greenberg SM, Iadecola C, et al. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the american heart association/american stroke association. Stroke. 2011;42(9):2672–713.PubMedPubMedCentralCrossRefGoogle Scholar
- 4.•• Benavente OR, Hart RG, McClure LA, Szychowski JM, Coffey CS, Pearce LA, et al. Effects of clopidogrel added to aspirin in patients with recent lacunar stroke. N Engl J Med. 2012;367(9):817–25. Sole reported phase III randomized trial assessing optimal antithrombotic therapy in lacunar stroke patients. Google Scholar
- 8.• Shoamanesh A, Pearce LA, Bazan C, Catanese L, McClure LA, Sharma M, et al. Microbleeds in the secondary prevention of small subcortical strokes trial: stroke, mortality, and treatment interactions. Ann Neurol. 2017;82(2):196–207. First subgroup analysis assessing treatment interactions between random assignment to antiplatelet therapy (aspirin/clopidogrel vs. aspirin) and cerebral microbleeds for the outcome of recurrent stroke or death.PubMedPubMedCentralCrossRefGoogle Scholar
- 13.• Wardlaw JM, Smith C, Dichgans M. Small vessel disease: mechanisms and clinical implications. Lancet Neurol. 2019; Authoratative and current reivew on the mechanisms and implications of cerebral small vessel disease. Google Scholar
- 25.•• Kwok CS, Shoamanesh A, Copley HC, Myint PK, Loke YK, Benavente OR. Efficacy of antiplatelet therapy in secondary prevention following lacunar stroke: pooled analysis of randomized trials. Stroke. 2015;46(4):1014–23. Comprehensive systematic review and meta-analysis on antiplatelet therapy following lacunar stroke.PubMedCrossRefGoogle Scholar
- 29.CAST: randomised placebo-controlled trial of early aspirin use in 20,000 patients with acute ischaemic stroke. CAST (Chinese Acute Stroke Trial) Collaborative Group. Lancet. 1997;349(9066):1641–9.Google Scholar
- 30.The International Stroke Trial (IST): a randomised trial of aspirin, subcutaneous heparin, both, or neither among 19435 patients with acute ischaemic stroke. International Stroke Trial Collaborative Group. Lancet. 1997;349(9065):1569–81.Google Scholar
- 33.Diener HC, Bogousslavsky J, Brass LM, Cimminiello C, Csiba L, Kaste M, et al. Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial. Lancet. 2004;364(9431):331–7.PubMedCrossRefGoogle Scholar
- 44.Shoamanesh A, Charidimou A, Sharma M, Hart RG. Should patients with ischemic stroke or transient ischemic attack with atrial fibrillation and microbleeds be anticoagulated? Stroke. 2017.Google Scholar
- 45.• Wilson D, Ambler G, Lee KJ, Lim JS, Shiozawa M, Koga M, et al. Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies. Lancet Neurol. 2019; Comprehensive pooled analysis of future cerebrovascular events in ischemic stroke/TIA patients with cerebral microbleeds on MRI.Google Scholar
- 48.•• Collaboration R. Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial. Lancet. 2019; Sole randomized trial assessing antiplatelet therapy compared with no antiplatelet therapy following intracerebral hemorrhage.Google Scholar
- 49.• Al-Shahi Salman R, Minks DP, Mitra D, Rodrigues MA, Bhatnagar P, du Plessis JC, et al. Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial. Lancet Neurol. 2019; First subgroup analysis investigating treatment interactions with MRI markers of hemorrhage-prone cerebral small vessel disease and random assignment to antiplatelet therapy vs. no antiplatelet therapy in intracerebral hemorrhage patients.Google Scholar