Reviews/P2Y12 Antiplatelets/Extended DAPT reduces MI but increases non-cardiac mortality vs 12-month DAPT
Duration · P2Y12-DUR-03 · v1
Borderline: within 4 points of the Uncertain/Doubtful boundary, so a re-grade could land either side.
This claim makes two separate promises at once: that taking dual antiplatelet drugs longer than a year cuts heart attacks, and that it raises deaths from non-heart causes, both compared with stopping at twelve months. The non-heart-death half comes almost entirely from one re-analysis of a single trial [1], where the difference was small (0.9 vs 0.5 percent) and the authors themselves say it may be down to chance; a separate registry [7] found no difference in five-year deaths. The heart-attack half has no direct trial comparing extended against twelve-month treatment: the supporting studies either compare six against twelve months [4], report only a lumped-together outcome [2], or are observational [11], and one large registry [6] points the other way. The strongest direct evidence on heart attacks sits in meta-analyses that the review's study-type filter removed [10]. Because each half is carried by different, weak, and partly mismatched sources, the panel treated the combined statement as reaching beyond what the eligible evidence supports.
The eligible corpus supports the direction of both limbs only weakly. For heart attacks, [4] shows more myocardial infarction with six than with twelve or more months of therapy (1.8 vs 0.8 percent, HR 2.41) and [11] shows lower myocardial infarction with therapy beyond twelve months (0.8 vs 1.9 percent, P=0.005), while [2] reduces only a composite endpoint (HR 0.82, 0.69 to 0.98) and the registry [6] links discontinuation after nine months to lower myocardial infarction (HR 0.75). For non-cardiac mortality, [1] is the sole direct source, reporting 0.9 vs 0.5 percent (P=0.01) with continued thienopyridine and noting this may be a chance finding, while [7] found no effect on five-year mortality (HR 1.3, 0.9 to 1.8). The most direct head-to-head myocardial-infarction evidence, [10] (relative risk 0.68), was excluded by the study-type filter. The contested point: The division is whether each limb survives on eligible primary evidence: the non-cardiac-mortality signal is a single, self-flagged, unreplicated post-hoc result in [1] that [7] does not confirm, and the myocardial-infarction reduction has no direct extended-versus-twelve-month RCT breakout, with [6] contradicting it. The excluded meta-analysis [10] would strengthen the myocardial-infarction limb but cannot be cited.
All 18 papers behind this claim with their DOIs and what each does to it, the panel’s arbitration, the evidence gap map and the open research questions. Free, and sent to your inbox.
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One reviewer's only job is to attack the finding. The challenges below were weighed before the grade was set.
Compound claim: both limbs must hold, yet each is carried by different studies with different comparators. The non-cardiac-mortality limb rests on a single source [1] where the signal is self-described as potentially chance ('may be a chance finding') and is not replicated by [7] (no 5-year mortality difference).
The MI-reduction limb has no direct eligible RCT breakout: [4] is a 6-vs-12-month mirror, [2] reports only a composite, and [11] is observational and confounded. The registry [6] actively contradicts it (discontinuation after 9 months linked to lower MI). The strongest direct evidence (NMA [10]) is excluded by the study-type filter.
Where it remains uncertain. Registry [6] links discontinuation after nine months to lower myocardial infarction (HR 0.75), pointing opposite to the first limb, and the strongest direct myocardial-infarction evidence [10] is excluded by the study-type filter.
Aleatory
Non-cardiovascular deaths in [1] are so few (0.9 vs 0.5 percent) that the authors state the difference may be a chance finding.
Epistemic
The strongest extended-versus-twelve-month myocardial-infarction result, [10] (relative risk 0.68), is removed by the study-type filter, leaving no direct eligible RCT breakout.
Inferential
[2] and [11] compare extended DAPT against aspirin monotherapy, not twelve-month DAPT as the claim specifies, so their results do not map cleanly onto the stated contrast.
The load-bearing papers from a corpus of 18, each classified by what it does to the claim. Every DOI is taken from the corpus the claim was graded on.
Primary (and essentially sole) eligible support for the non-cardiac-mortality limb; extended thienopyridine vs stopping at 12 months.
“Cancer-related death in association with thienopyridine therapy was mainly not related to bleeding and may be a chance finding.”
Panel auditInternal validity: medium · scope of inference: Patients >12 months after DES/BMS placement, extended thienopyridine vs placebo, cause-specific mortality.Key limitations: very low event rates · post-hoc · cancer imbalance possibly chance · no MI contrast reported
Extended DAPT lowers a composite including nonfatal MI vs aspirin monotherapy; no standalone MI figure.
“hazard ratio, 0.82; 95% confidence interval [CI], 0.69 to 0.98; P = 0.03”
Panel auditInternal validity: medium · scope of inference: Event-free multivessel-disease patients 12 months after DES, extended DAPT vs aspirin alone.Key limitations: composite endpoint only · open-label · MI and non-cardiac mortality not broken out
Indirect (mirror) support for the MI-reduction limb: shorter DAPT raises MI.
“myocardial infarction occurred more frequently in the 6-month DAPT group than in the 12-month or longer DAPT group (24 [1·8%] patients vs ten [0·8%]; 2·41 [1·15-5·05]; p=0·02)”
Panel auditInternal validity: medium · scope of inference: ACS patients after PCI with current-generation DES, shorter vs standard-or-longer DAPT.Key limitations: comparator mixes 12-month and longer · open-label · wide non-inferiority margin
Counter-evidence: discontinuation after 9 months associated with LOWER MI, contradicting the MI-reduction limb.
“myocardial infarction (HR, 0.75 [95% CI, 0.69-0.82])”
Panel auditInternal validity: low · scope of inference: VA patients with second-generation DES, observational DAPT-duration outcomes to 13 years.Key limitations: observational · confounding by indication · duration cut at 9 months not extended vs 12
4 of 18 papers shown. The full review lists all of them, with the panel’s arbitration →
Claims are graded at each quarterly release, and re-graded between releases only when a pivotal trial lands. Every change is a new version of the claim.
Both limbs are supported only weakly and the mortality limb is a single, self-qualified, unreplicated signal, so the conjunction cannot be held above Uncertain.
Release 2026-q4 re-graded every claim from its corpus under protocol v0.19. An earlier release's grade is shown for the record; it came from an earlier protocol and is not a movement.
Assumptions that carry weight but are not themselves established.
The panel records the gap that would most move the claim, and the study that would close it.
Replication of the non-cardiac-mortality signal. The mortality limb hinges on one self-qualified post-hoc result [1] not confirmed by [7]. The panel rates this the highest-importance open gap for the claim, and names the study design that would close it: A prospectively powered trial or pooled individual-patient analysis tracking cause-specific non-cardiovascular death by DAPT duration.
Open question: Does extended DAPT reduce myocardial infarction when compared directly with exactly twelve-month DAPT? Why it is still open: No eligible primary trial in the corpus provides this direct breakout; [4] is six-versus-twelve, [2] reports only a composite, and [10] is excluded.
Priors is a sceptical first reader, not peer review, and not medical advice.
Release 2026-q4 · graded 21 Oct 2026 · protocol v0.19