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Cited by 6,943Antiplatelet Therapy and Cardiovascular DiseasesAcute Myocardial Infarction ResearchAcute Ischemic Stroke Management

Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients

Open access
Collaboration, A. T.·2002·BMJ
DOI 10.1136/bmj.324.7329.71PMC PMC64503
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Abstract

OBJECTIVE: To determine the effects of antiplatelet therapy among patients at high risk of occlusive vascular events. DESIGN: Collaborative meta-analyses (systematic overviews). INCLUSION CRITERIA: Randomised trials of an antiplatelet regimen versus control or of one antiplatelet regimen versus another in high risk patients (with acute or previous vascular disease or some other predisposing condition) from which results were available before September 1997. Trials had to use a method of randomisation that precluded prior knowledge of the next treatment to be allocated and comparisons had to be unconfounded-that is, have study groups that differed only in terms of antiplatelet regimen. STUDIES REVIEWED: 287 studies involving 135 000 patients in comparisons of antiplatelet therapy versus control and 77 000 in comparisons of different antiplatelet regimens. MAIN OUTCOME MEASURE: "Serious vascular event": non-fatal myocardial infarction, non-fatal stroke, or vascular death. RESULTS: Overall, among these high risk patients, allocation to antiplatelet therapy reduced the combined outcome of any serious vascular event by about one quarter; non-fatal myocardial infarction was reduced by one third, non-fatal stroke by one quarter, and vascular mortality by one sixth (with no apparent adverse effect on other deaths). Absolute reductions in the risk of having a serious vascular event were 36 (SE 5) per 1000 treated for two years among patients with previous myocardial infarction; 38 (5) per 1000 patients treated for one month among patients with acute myocardial infarction; 36 (6) per 1000 treated for two years among those with previous stroke or transient ischaemic attack; 9 (3) per 1000 treated for three weeks among those with acute stroke; and 22 (3) per 1000 treated for two years among other high risk patients (with separately significant results for those with stable angina (P=0.0005), peripheral arterial disease (P=0.004), and atrial fibrillation (P=0.01)). In each of these high risk categories, the absolute benefits substantially outweighed the absolute risks of major extracranial bleeding. Aspirin was the most widely studied antiplatelet drug, with doses of 75-150 mg daily at least as effective as higher daily doses. The effects of doses lower than 75 mg daily were less certain. Clopidogrel reduced serious vascular events by 10% (4%) compared with aspirin, which was similar to the 12% (7%) reduction observed with its analogue ticlopidine. Addition of dipyridamole to aspirin produced no significant further reduction in vascular events compared with aspirin alone. Among patients at high risk of immediate coronary occlusion, short term addition of an intravenous glycoprotein IIb/IIIa antagonist to aspirin prevented a further 20 (4) vascular events per 1000 (P<0.0001) but caused 23 major (but rarely fatal) extracranial bleeds per 1000. CONCLUSIONS: Aspirin (or another oral antiplatelet drug) is protective in most types of patient at increased risk of occlusive vascular events, including those with an acute myocardial infarction or ischaemic stroke, unstable or stable angina, previous myocardial infarction, stroke or cerebral ischaemia, peripheral arterial disease, or atrial fibrillation. Low dose aspirin (75-150 mg daily) is an effective antiplatelet regimen for long term use, but in acute settings an initial loading dose of at least 150 mg aspirin may be required. Adding a second antiplatelet drug to aspirin may produce additional benefits in some clinical circumstances, but more research into this strategy is needed.

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  • The Antithrombotic Trialists' Collaboration demonstrated a non-significant 7% reduction in risk of vascular events in patients who were at high risk because of diabetes.

    “A further analysis by the Antithrombotic Trialists' Collaboration demonstrated a non-significant 7% reduction in risk of vascular events in patients who were at high risk because of the presence of diabetes.454”

    From European Guidelines on cardiovascular disease prevention in clinical practice (version 2012) (2012) · cites this paper as [454]

  • Aspirin is effective in the treatment of acute myocardial infarction and in secondary prevention of cardiovascular disease.

    “Aspirin, a potent anti-inflammatory molecule, is effective in the treatment of acute myocardial infarction and in secondary prevention of CVD”

    From Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty (2018) · cites this paper as [251]

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Research works printed but not linked: 4

  1. Romeo F, Ruvolo G, Martuscelli E, Comito M, Cardona N, Colistra C, et al. Ticlopidine in the prevention of the block of aorto-coronary by-pass. In: Proceedings of satellite symposium of 83rd congress of Italian Society of Inter- nal Medicine. Rome: ISIM, 1982:155-60.
  2. Massie BM, Shah NB. Evolving trends in the epidemiology of heart fail- ure: a rationale for prevention. Am Heart J 1997;133:703-12.
  3. Herbert JM, Lemat A, Samama M, Maffrand JP. The antiaggregating and antithrombotic activity of ticlopidine. Thromb Haemost 1996;76:94-8.
  4. Massie BM. Antithrombotic therapy in heart failure: new perspectives. Eur Heart J 2000;2:E13-7.

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Authors
Collaboration, A. T.
Venue
BMJ
Publisher
BMJ
Published
2002-01-12
Volume
324
Issue
7329
Pages
71-86
ISSN
  • 0007-1447 (ISSN-L)
  • 0959-8138
  • 1468-5833
DOI
10.1136/bmj.324.7329.71
PMC
PMC64503
OpenAlex
W2024352468
Cited by
6,943
References
70
Citations by year
2026: 78 · 2025: 117 · 2024: 126 · 2023: 150 · 2022: 163 · 2021: 216 · 2020: 194 · 2019: 238 · 2018: 201 · 2017: 277 · 2016: 267 · 2015: 281 · 2014: 326 · 2013: 344 · 2012: 417
FWCI
46.93
Type
journal article
Language
en
Open access
Locations
  • BMJ (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Research Explorer (The University of Manchester) (publishedVersion)
  • LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
  • Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
  • IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
  • Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
Funders
  • Wellcome Trust
  • British Heart Foundation
  • University of Oxford
  • European Commission
  • Medical Research Council
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Antiplatelet Therapy and Cardiovascular Diseases
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Acute Myocardial Infarction Research
  • Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
Keywords
antiplatelet therapy, aspirin, clopidogrel, vascular events, myocardial infarction, stroke, vascular death, high-risk patients, acute myocardial infarction, acute stroke, old myocardial infarction, stroke history, stable angina, peripheral arterial disease, atrial fibrillation, bleeding risk, risk-benefit assessment
MeSH terms
Aspirin, Cardiovascular Diseases, Drug Administration Schedule, Drug Therapy, Combination, Humans, Myocardial Infarction, Platelet Aggregation Inhibitors, Randomized Controlled Trials as Topic, Risk Assessment, Stroke

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