Trial reportThe New England journal of medicine2012
Effects of clopidogrel added to aspirin in patients with recent lacunar stroke.
Trial report in The New England journal of medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00059306 (Secondary Prevention of Small Subcortical Strokes), which is not on this map. Cited by 273 papers, 25 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Secondary Prevention of Small Subcortical Strokes (SPS3) Trial
Who cites it
273 citing papers in PubMed, 25 syntheses or guidelines pooled it, 679 citations in OpenAlex.
- The bleeding costs of intensive vs. less intensive antithrombotic strategies: a meta-regression analysis.European heart journal. Quality of care & clinical outcomes · 2026Pooled it
- Tailoring dual antiplatelet therapy for stroke prevention: a meta-analysis of timing, duration, regimen, and stroke subtypes.Frontiers in pharmacology · 2025Pooled it
- Dual antiplatelet therapy use after non-cardioembolic ischemic stroke or transient ischemic attack: a meta-analysis of trials and cohort studies.Frontiers in neurology · 2025Pooled it
- European stroke organisation (ESO) guideline on cerebral small vessel disease, part 2, lacunar ischaemic stroke.European stroke journal · 2024Guideline
- Chinese Stroke Association guidelines for clinical management of ischaemic cerebrovascular diseases: executive summary and 2023 update.Stroke and vascular neurology · 2023Guideline
- Antiplatelet therapy and outcomes after aneurysmal subarachnoid hemorrhage: A systematic review and meta-analysis.Clinical neurology and neurosurgery · 2023Pooled it
- Contemporary antiplatelet therapy for secondary stroke prevention: a narrative review of current literature and guidelines.Stroke and vascular neurology · 2022Pooled it
- Antithrombotic therapy to prevent cognitive decline in people with small vessel disease on neuroimaging but without dementia.The Cochrane database of systematic reviews · 2022Pooled it
- The role ofExpert review of clinical pharmacology · 2022Pooled it
- The Importance of Platelets Response during Antiplatelet Treatment after Ischemic Stroke-Between Benefit and Risk: A Systematic Review.International journal of molecular sciences · 2022Pooled it
- Efficacy and safety of concomitant use of proton pump inhibitors with aspirin-clopidogrel dual antiplatelet therapy in coronary heart disease: A systematic review and meta-analysis.Frontiers in pharmacology · 2022Pooled it
- Multiple versus fewer antiplatelet agents for preventing early recurrence after ischaemic stroke or transient ischaemic attack.The Cochrane database of systematic reviews · 2020Pooled it
- Cilostazol for Secondary Prevention of Stroke and Cognitive Decline: Systematic Review and Meta-Analysis.Stroke · 2020Pooled it
- Optimal Duration of Aspirin Plus Clopidogrel After Ischemic Stroke or Transient Ischemic Attack.Stroke · 2019Pooled it
- Clopidogrel and aspirin after ischemic stroke or transient ischemic attack: an updated systematic review and meta-analysis of randomized clinical trials.Journal of thrombosis and thrombolysis · 2019Pooled it
- Clinical Significance of Magnetic Resonance Imaging Markers of Vascular Brain Injury: A Systematic Review and Meta-analysis.JAMA neurology · 2019Pooled it
- Clopidogrel plus aspirin versus aspirin alone for acute minor ischaemic stroke or high risk transient ischaemic attack: systematic review and meta-analysis.BMJ (Clinical research ed.) · 2018Pooled it
- Differences in relative and absolute effectiveness of oral P2YHeart (British Cardiac Society) · 2018Pooled it
- Early time course of major bleeding on antiplatelet therapy after TIA or ischemic stroke.Neurology · 2018Pooled it
- Clopidogrel plus aspirin versus aspirin alone for preventing cardiovascular events.The Cochrane database of systematic reviews · 2017Pooled it
213 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
- Commented on by[Not Available].2013
Authors and funding
7 authors.
Funding
Abstract
backgroundLacunar infarcts are a frequent type of stroke caused mainly by cerebral small-vessel disease. The effectiveness of antiplatelet therapy for secondary prevention has not been defined.
methodsWe conducted a double-blind, multicenter trial involving 3020 patients with recent symptomatic lacunar infarcts identified by magnetic resonance imaging. Patients were randomly assigned to receive 75 mg of clopidogrel or placebo daily; patients in both groups received 325 mg of aspirin daily. The primary outcome was any recurrent stroke, including ischemic stroke and intracranial hemorrhage.
resultsThe participants had a mean age of 63 years, and 63% were men. After a mean follow-up of 3.4 years, the risk of recurrent stroke was not significantly reduced with aspirin and clopidogrel (dual antiplatelet therapy) (125 strokes; rate, 2.5% per year) as compared with aspirin alone (138 strokes, 2.7% per year) (hazard ratio, 0.92; 95% confidence interval [CI], 0.72 to 1.16), nor was the risk of recurrent ischemic stroke (hazard ratio, 0.82; 95% CI, 0.63 to 1.09) or disabling or fatal stroke (hazard ratio, 1.06; 95% CI, 0.69 to 1.64). The risk of major hemorrhage was almost doubled with dual antiplatelet therapy (105 hemorrhages, 2.1% per year) as compared with aspirin alone (56, 1.1% per year) (hazard ratio, 1.97; 95% CI, 1.41 to 2.71; P<0.001). Among classifiable recurrent ischemic strokes, 71% (133 of 187) were lacunar strokes. All-cause mortality was increased among patients assigned to receive dual antiplatelet therapy (77 deaths in the group receiving aspirin alone vs. 113 in the group receiving dual antiplatelet therapy) (hazard ratio, 1.52; 95% CI, 1.14 to 2.04; P=0.004); this difference was not accounted for by fatal hemorrhages (9 in the group receiving dual antiplatelet therapy vs. 4 in the group receiving aspirin alone).
conclusionsAmong patients with recent lacunar strokes, the addition of clopidogrel to aspirin did not significantly reduce the risk of recurrent stroke and did significantly increase the risk of bleeding and death. (Funded by the National Institute of Neurological Disorders and Stroke and others; SPS3 ClinicalTrials.gov number, NCT00059306.).
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.