Reviews/P2Y12 Antiplatelets/Prasugrel harm in prior stroke patients
Pras · P2Y12-PRAS-03 · v1
The claim is that prasugrel causes more overall harm than clopidogrel in people who have had a prior stroke. The one eligible trial actually run in stroke patients [1] found similar effectiveness and no excess bleeding for prasugrel, which argues against the claim. The main head-to-head trial [4] shows prasugrel does cause more major bleeding overall, but in heart-attack patients undergoing stenting, where it also prevented more clots and did not change death rates, and it reports no separate result for prior-stroke patients. The specific number showing net harm in prior-stroke patients comes only from review articles [15][16], which the panel excluded because they are secondary summaries rather than primary studies. With the quantitative signal sitting outside the weighable evidence and the one stroke trial pointing the other way, the panel judged the claim poorly supported by the eligible corpus.
The only eligible primary trial conducted in a stroke population [1] found comparable efficacy (primary endpoint RR 1.05, 95% CI 0.76-1.44) and no significant difference in bleeding, with life-threatening bleeding numerically favouring prasugrel (RR 0.77, 0.41-1.42) and no safety concerns identified. The pivotal head-to-head RCT [4] confirms prasugrel increases major bleeding overall (HR 1.32, 95% CI 1.03-1.68) while reducing ischaemic events and leaving mortality unchanged, but in an ACS/PCI population and with no prior-stroke subgroup in its text. The quantitative net-harm figure for prior stroke or TIA (HR 1.54, 95% CI 1.02-2.32) appears only in review papers [15][16] summarising a TRITON-TIMI 38 subanalysis. No eligible primary paper reports a prior-stroke subgroup, so the corpus does not quantify net harm in the population the claim names. The contested point: The evidence divides on whether the net-harm-in-prior-stroke subanalysis can be weighed at all: it exists in the corpus only inside study-type-excluded reviews [15][16], while the one eligible stroke-population trial [1] points the opposite way at a low 3.75 mg dose in a different indication. The dispute is therefore not about the direction of a measured effect but about whether the relevant measurement is admissible evidence here.
All 17 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.
The quantitative net-harm-in-prior-stroke evidence exists only in study-type-excluded review papers ([15], [16]: TRITON-TIMI 38 subanalysis HR 1.54, 1.02-2.32); no eligible primary trial in the corpus reports a prior-stroke subgroup, so the claim's quantitative basis is absent from weighable evidence.
The only eligible trial actually conducted in stroke patients ([1], PRASTRO-I) used low-dose prasugrel 3.75 mg for acute secondary prevention, not full-dose prasugrel in ACS/PCI patients with remote prior stroke; its null safety result may not transfer to the dose and setting the claim describes.
Where it remains uncertain. The quantitative net-harm-in-prior-stroke signal (HR 1.54, 1.02-2.32) exists only in study-type-excluded reviews [15][16], while the one eligible stroke trial [1] used a low 3.75 mg dose in acute secondary prevention, not the full-dose ACS/PCI setting the claim describes.
Aleatory
Life-threatening bleeding in [1] rested on 18 vs 23 patients, a small event count whose wide interval (RR 0.77, 0.41-1.42) spans both directions.
Epistemic
No eligible primary trial ([1], [4]) reports a prior-stroke subgroup for net clinical harm, so the population the claim names is not directly measured in weighable evidence.
Inferential
[1] tested prasugrel 3.75 mg for acute non-cardioembolic stroke secondary prevention; transferring its null safety result to full-dose ACS/PCI patients with remote prior stroke is an unverified leap.
The load-bearing papers from a corpus of 17, each classified by what it does to the claim. Every DOI is taken from the corpus the claim was graded on.
In a randomised trial of prasugrel vs clopidogrel in stroke patients, bleeding was not greater with prasugrel (numerically lower), contradicting a net-harm signal.
“73 (4%) of 1885 patients in the prasugrel group and 69 (4%) of 1862 patients in the clopidogrel group reached the primary endpoint (RR 1·05, 95% CI 0·76-1·44).”
Panel auditInternal validity: high · scope of inference: Japanese patients aged 20-74 with non-cardioembolic ischaemic stroke 1-26 weeks prior, treated with low-dose (3.75 mg) prasugrel.Key limitations: low 3.75 mg prasugrel dose · Japanese-only population · non-inferiority not confirmed · recent stroke not remote prior stroke
Establishes prasugrel's bleeding liability in ACS/PCI, but this is an overall result with no prior-stroke subgroup reported, so it cannot establish net harm specifically in prior stroke.
“Overall mortality did not differ significantly between treatment groups.”
Panel auditInternal validity: high · scope of inference: Moderate-to-high-risk ACS patients undergoing PCI; prasugrel reduced ischaemic events but increased major and fatal bleeding overall.Key limitations: prior-stroke subgroup not in this abstract · overall ACS/PCI population only
2 of 17 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.
Eligible primary evidence does not support, and partly contradicts, net harm in prior stroke, but the direct trial's non-comparable low dose and the missing subgroup prevent a full refutation.
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.
Prior-stroke subgroup from a full-dose head-to-head RCT. The claim concerns combined ischaemic-plus-bleeding harm in prior-stroke patients, which no eligible primary trial reports; the pivotal RCT [4] omits the subgroup and [1] uses a non-comparable dose. The panel rates this the highest-importance open gap for the claim, and names the study design that would close it: A primary report or pre-specified subgroup analysis of full-dose prasugrel vs clopidogrel net clinical outcomes in ACS/PCI patients with remote prior stroke.
Open question: Does full-dose prasugrel versus clopidogrel produce net clinical harm specifically in ACS/PCI patients with remote prior stroke? Why it is still open: No eligible primary trial in the corpus reports a prior-stroke subgroup; [4] omits it and [1] used a low dose in a different indication.
Priors is a sceptical first reader, not peer review, and not medical advice.
Release 2026-q4 · graded 21 Oct 2026 · protocol v0.19