{ "format_version": 3, "claim_natural": "Daily low-dose aspirin reduces the risk of recurrent non-fatal myocardial infarction in patients with prior cardiovascular disease, per the Antithrombotic Trialists' Collaboration meta-analysis.", "claim_formal": { "subject": "Daily low-dose aspirin and recurrent non-fatal myocardial infarction in patients with prior cardiovascular disease, as assessed by the Antithrombotic Trialists' (ATT) Collaboration meta-analyses", "is_time_sensitive": false, "sub_claims": [ { "id": "SC1", "property": "The ATT Collaboration meta-analysis found daily low-dose aspirin associated with a reduction in non-fatal myocardial infarction among patients with prior cardiovascular disease", "operator": ">=", "threshold": 2, "operator_note": "SC1 (association) holds when at least 2 verified quotations from the ATT meta-analysis publications report that low-dose aspirin / antiplatelet therapy is associated with a reduction in non-fatal myocardial infarction (or the coronary-event composite that includes non-fatal MI) among patients with prior cardiovascular disease." }, { "id": "SC2", "property": "The ATT Collaboration meta-analysis pools randomized controlled trials, giving the observed reduction a causal (not merely associational) basis", "operator": ">=", "threshold": 2, "operator_note": "SC2 (causation) holds when at least 2 verified quotations establish that the ATT meta-analysis pools randomized controlled trials. Random allocation removes confounding, so a reduction observed consistently across pooled RCTs supports a causal interpretation -- this meets the Proof Engine's gold-standard criterion for SC-causation (RCTs / controlled experiments)." } ], "compound_operator": "AND", "operator_note": "The claim uses causal language ('reduces the risk'), so it is decomposed into an association sub-claim (SC1) and a causation sub-claim (SC2); both must hold for a PROVED verdict (compound_operator AND). The claim is explicitly attributed to 'the Antithrombotic Trialists' Collaboration meta-analysis', so the proof evaluates it against the ATT Collaboration's own publications: the 2002 BMJ collaborative overview of antiplatelet therapy in high-risk patients and the 2009 Lancet individual-participant-data meta-analysis of aspirin in primary and secondary prevention. 'Patients with prior cardiovascular disease' is interpreted as the secondary-prevention / high-risk population the ATT analyses studied (acute or previous occlusive vascular disease). 'Recurrent non-fatal myocardial infarction' is interpreted as non-fatal MI events occurring within that established-disease population; the ATT analyses include an explicit 'previous myocardial infarction' patient category in which any subsequent non-fatal MI is unambiguously recurrent. 'Low-dose aspirin' is interpreted as the 75-150 mg/day range the ATT 2002 analysis found 'at least as effective as higher daily doses'. Source-count thresholds are set to 2 (not the default 3): by construction the claim restricts the evidence base to one named source program (the ATT Collaboration meta-analysis), which produced exactly two landmark meta-analyses on this question -- both peer-reviewed in top-tier journals (BMJ, Lancet), each pooling large randomized-trial datasets, and funded by public/charitable bodies (UK Medical Research Council, British Heart Foundation, Cancer Research UK, EC Biomed) with no aspirin-manufacturer funding. No conflict of interest favoring the claim was identified." }, "evidence": { "B1": { "type": "empirical", "label": "SC1 - ATT 2002 BMJ: non-fatal MI reduced by one third in high-risk patients", "sub_claim": "SC1", "source": { "name": "Antithrombotic Trialists' Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002;324:71-86 (full text via PubMed Central, PMC64503).", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC64503/", "quote": "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" }, "verification": { "status": "verified", "method": "full_quote", "coverage_pct": null, "fetch_mode": "live", "credibility": { "domain": "nih.gov", "source_type": "government", "tier": 5, "flags": [], "note": "Government domain (.gov)" } }, "extraction": { "value": "verified", "value_in_quote": true, "quote_snippet": "Overall, among these high risk patients, allocation to antiplatelet therapy redu" } }, "B2": { "type": "empirical", "label": "SC1 - ATT 2002 BMJ: low-dose aspirin (75-150 mg) at least as effective as higher doses", "sub_claim": "SC1", "source": { "name": "Antithrombotic Trialists' Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002;324:71-86 (full text via PubMed Central, PMC64503).", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC64503/", "quote": "Aspirin was the most widely studied antiplatelet drug, with doses of 75-150 mg daily at least as effective as higher daily doses." }, "verification": { "status": "verified", "method": "full_quote", "coverage_pct": null, "fetch_mode": "live", "credibility": { "domain": "nih.gov", "source_type": "government", "tier": 5, "flags": [], "note": "Government domain (.gov)" } }, "extraction": { "value": "verified", "value_in_quote": true, "quote_snippet": "Aspirin was the most widely studied antiplatelet drug, with doses of 75-150 mg d" } }, "B3": { "type": "empirical", "label": "SC1 - ATT 2009 Lancet: aspirin reduces serious vascular events in secondary-prevention trials", "sub_claim": "SC1", "source": { "name": "Antithrombotic Trialists' (ATT) Collaboration. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet 2009;373:1849-60 (abstract via PubMed, PMID 19482214).", "url": "https://pubmed.ncbi.nlm.nih.gov/19482214/", "quote": "In the secondary prevention trials, aspirin allocation yielded a greater absolute reduction in serious vascular events" }, "verification": { "status": "verified", "method": "full_quote", "coverage_pct": null, "fetch_mode": "live", "credibility": { "domain": "nih.gov", "source_type": "government", "tier": 5, "flags": [], "note": "Government domain (.gov)" } }, "extraction": { "value": "verified", "value_in_quote": true, "quote_snippet": "In the secondary prevention trials, aspirin allocation yielded a greater absolut" } }, "B4": { "type": "empirical", "label": "SC2 - ATT 2002 BMJ: inclusion restricted to randomised trials", "sub_claim": "SC2", "source": { "name": "Antithrombotic Trialists' Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002;324:71-86 (full text via PubMed Central, PMC64503).", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC64503/", "quote": "Randomised trials of an antiplatelet regimen versus control or of one antiplatelet regimen versus another in high risk patients" }, "verification": { "status": "verified", "method": "full_quote", "coverage_pct": null, "fetch_mode": "live", "credibility": { "domain": "nih.gov", "source_type": "government", "tier": 5, "flags": [], "note": "Government domain (.gov)" } }, "extraction": { "value": "verified", "value_in_quote": true, "quote_snippet": "Randomised trials of an antiplatelet regimen versus control or of one antiplatel" } }, "B5": { "type": "empirical", "label": "SC2 - ATT 2009 Lancet: meta-analysis of individual participant data from randomised trials", "sub_claim": "SC2", "source": { "name": "Antithrombotic Trialists' (ATT) Collaboration. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet 2009;373:1849-60 (abstract via PubMed, PMID 19482214).", "url": "https://pubmed.ncbi.nlm.nih.gov/19482214/", "quote": "collaborative meta-analysis of individual participant data from randomised trials" }, "verification": { "status": "verified", "method": "full_quote", "coverage_pct": null, "fetch_mode": "live", "credibility": { "domain": "nih.gov", "source_type": "government", "tier": 5, "flags": [], "note": "Government domain (.gov)" } }, "extraction": { "value": "verified", "value_in_quote": true, "quote_snippet": "collaborative meta-analysis of individual participant data from randomised trial" } }, "A1": { "type": "computed", "label": "SC1 verified source count", "sub_claim": "SC1", "method": "count(verified sc1 citations) = 3", "result": "3", "depends_on": [ "B1", "B2", "B3" ] }, "A2": { "type": "computed", "label": "SC2 verified source count", "sub_claim": "SC2", "method": "count(verified sc2 citations) = 2", "result": "2", "depends_on": [ "B4", "B5" ] } }, "cross_checks": [ { "description": "SC1: independent ATT meta-analysis publications consulted", "fact_ids": [ "B1", "B2", "B3" ], "agreement": true, "n_sources_consulted": 3, "n_sources_verified": 3, "sources": { "sc1_att2002_mi": "verified", "sc1_att2002_dose": "verified", "sc1_att2009": "verified" }, "independence_note": "SC1 draws on two distinct ATT meta-analyses published seven years apart in different journals (BMJ 2002, Lancet 2009) using different methods (tabular data vs individual participant data) and overlapping but non-identical trial sets. B1 and B2 are two distinct findings (the non-fatal-MI reduction and the low-dose equivalence) from the 2002 BMJ paper; B3 is from the independent 2009 Lancet meta-analysis.", "coi_flags": [] }, { "description": "SC2: independent ATT meta-analysis publications consulted", "fact_ids": [ "B4", "B5" ], "agreement": true, "n_sources_consulted": 2, "n_sources_verified": 2, "sources": { "sc2_att2002": "verified", "sc2_att2009": "verified" }, "independence_note": "SC2 is confirmed by both ATT publications independently: the 2002 BMJ paper restricts inclusion to 'Randomised trials', and the 2009 Lancet paper is a 'collaborative meta-analysis of individual participant data from randomised trials'. Two separate publications each document the randomized-controlled-trial basis.", "coi_flags": [] } ], "adversarial_checks": [ { "question": "Does the ATT meta-analysis actually report a reduction in non-fatal myocardial infarction, or is the attribution wrong?", "verification_performed": "Fetched and read the ATT 2002 BMJ meta-analysis (PMC64503) and the ATT 2009 Lancet meta-analysis abstract (PubMed 19482214); searched for the verbatim findings on non-fatal MI and secondary prevention.", "finding": "The attribution is accurate. The 2002 BMJ ATT meta-analysis explicitly states that, among high-risk patients, 'non-fatal myocardial infarction was reduced by one third'. The 2009 Lancet ATT meta-analysis reports that in secondary-prevention trials aspirin reduced serious vascular events and coronary events. No mismatch between the claim and the named source was found.", "breaks_proof": false }, { "question": "Does the bleeding harm of aspirin negate or contradict the reduction in non-fatal MI?", "verification_performed": "Searched for counter-evidence on aspirin's bleeding harms and net benefit in secondary prevention (gastrointestinal / extracranial bleeding meta-analyses).", "finding": "Aspirin does increase major extracranial and gastrointestinal bleeding -- a well-documented, separate harm. This does not contradict the claim, which concerns the non-fatal-MI outcome specifically, not net clinical benefit. The ATT 2002 paper itself reports that in the high-risk categories 'the absolute benefits substantially outweighed the absolute risks of major extracranial bleeding'. Bleeding is a treatment trade-off, not evidence against the MI-reduction finding, so it does not break the proof.", "breaks_proof": false }, { "question": "Is the secondary-prevention benefit of aspirin contradicted by more recent evidence from the modern statin / revascularization era?", "verification_performed": "Searched 2020-2025 reviews and meta-analyses that question aspirin in secondary prevention, including recent commentary and a 2025 systematic review/meta-analysis of aspirin for secondary prevention of MI.", "finding": "Recent commentary debates whether aspirin's marginal benefit is as large in the modern treatment era and notes P2Y12 inhibitors as alternatives. However, a 2025 systematic review/meta-analysis still found aspirin reduced recurrent events by roughly a fifth in secondary prevention, and no source claims the ATT finding of reduced non-fatal MI was wrong or reversed. The direction of effect is confirmed by modern evidence; only the magnitude and its role relative to newer therapies are debated. This does not break a proof scoped to the ATT meta-analysis finding.", "breaks_proof": false }, { "question": "Does 'low-dose' aspirin specifically -- not antiplatelet therapy in general -- carry the non-fatal MI reduction?", "verification_performed": "Checked the ATT 2002 BMJ dose analysis and the scope of the 2009 Lancet meta-analysis.", "finding": "Supported. The ATT 2002 meta-analysis found 'doses of 75-150 mg daily at least as effective as higher daily doses' and identified aspirin as 'the most widely studied antiplatelet drug'; the 2009 ATT meta-analysis is explicitly an analysis of 'low-dose aspirin'. The 2002 paper notes the effects of doses below 75 mg are 'less certain', but standard low-dose aspirin (75-150 mg) is squarely within the supported range, so this does not break the proof.", "breaks_proof": false }, { "question": "Could 'recurrent' non-fatal MI be unsupported because the ATT meta-analysis pooled mixed prior-CVD populations rather than only prior-MI patients?", "verification_performed": "Reviewed the ATT meta-analysis patient categories in the 2002 BMJ and 2009 Lancet reports.", "finding": "The ATT meta-analysis explicitly includes a 'previous myocardial infarction' patient category among its high-risk groups (six secondary-prevention prior-MI trials in the 2009 analysis), in which a subsequent non-fatal MI is by definition recurrent. The proof interprets 'recurrent non-fatal MI in patients with prior CVD' as non-fatal MI events within the established-CVD secondary-prevention population the ATT analysed -- an interpretation documented in the operator_note that does not overstate the source -- so this does not break the proof.", "breaks_proof": false } ], "verdict": { "value": "PROVED", "qualified": false, "qualifier": null, "reason": null }, "key_results": { "n_holding": 2, "n_total": 2, "claim_holds": true, "sc1_verified_sources": 3, "sc2_verified_sources": 2 }, "generator": { "name": "proof-engine", "version": "1.34.1", "repo": "https://github.com/yaniv-golan/proof-engine", "generated_at": "2026-05-20" }, "sub_claim_results": [ { "id": "SC1", "n_confirming": 3, "threshold": 2, "holds": true }, { "id": "SC2", "n_confirming": 2, "threshold": 2, "holds": true } ], "proof_py_url": "/proofs/daily-low-dose-aspirin-reduces-the-risk-of-recurrent-non-fatal-myocardial/proof.py", "citation": { "doi": "10.5281/zenodo.20315066", "concept_doi": "10.5281/zenodo.20315065", "url": "https://proofengine.info/proofs/daily-low-dose-aspirin-reduces-the-risk-of-recurrent-non-fatal-myocardial/", "author": "Proof Engine", "cite_bib_url": "/proofs/daily-low-dose-aspirin-reduces-the-risk-of-recurrent-non-fatal-myocardial/cite.bib", "cite_ris_url": "/proofs/daily-low-dose-aspirin-reduces-the-risk-of-recurrent-non-fatal-myocardial/cite.ris" }, "depends_on": [] }