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Journal Club

Cerebrovascular

Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging

N Engl J Med | 2018

Rapid review note

Journal Club is a rapid, AI-assisted appraisal layer. It highlights study design, effect estimates, and practice relevance, but it is still a briefing, not a replacement for the paper.

For education only. Not medical advice.

Paper snapshot

Rapid study overview

Open paper

DOI

10.1056/NEJMoa1713973

PMID

29364767

PICO

Population

Patients with proximal MCA or ICA occlusion, last known well 6-16 hours, infarct <70 ml, ischemic tissue/infarct ratio ≥1.8, penumbra ≥15 ml

Intervention

Endovascular thrombectomy plus standard medical therapy

Comparator

Standard medical therapy alone

Outcomes

90-day modified Rankin scale (ordinal shift), functional independence (mRS 0-2), mortality, symptomatic ICH, serious adverse events

Design

Type

Multicenter randomized open-label trial with blinded outcome assessment

Randomized

Yes

Multicenter

Yes

Blinded

Outcome assessors only

Follow-up

90 days

Primary endpoint

Ordinal score on modified Rankin scale at 90 days

Secondary endpoints

  • Functional independence (mRS 0-2)
  • 90-day mortality
  • Symptomatic intracranial hemorrhage
  • Serious adverse events

Practice impact

What this means

DEFUSE 3 extends thrombectomy window to 6-16 hours using perfusion imaging selection. In 182 patients with proximal occlusion and favorable imaging mismatch, thrombectomy increased functional independence from 17% to 45% with mortality benefit. This supports changing practice for selected late-presenting patients.

Bottom line

Thrombectomy improves functional outcomes in selected late-presenting stroke patients with imaging mismatch

Strength of evidence

high

Recommendation

change practice

Why it matters

  • Large treatment effect (OR 2.77)
  • Clinically meaningful 28% absolute increase in functional independence
  • Mortality benefit with acceptable safety profile

What would change my mind

  • Larger trial showing no benefit in broader population
  • Long-term follow-up showing loss of early benefit
  • Cost-effectiveness analysis showing unfavorable ratio

Critical appraisal

How strong is the paper?

Methods critique

Risk of bias

Open-label design introduces performance bias; outcome assessors blinded mitigates detection bias

Confounding

Randomization balanced baseline characteristics; strict imaging selection criteria reduces confounding by infarct size

Missing data

Low attrition with 182/182 patients analyzed per protocol

Multiplicity

Multiple secondary endpoints without adjustment; primary endpoint analysis prespecified

Notes

  • Early termination for efficacy may overestimate effect
  • Imaging selection using RAPID software standardizes eligibility

Stats check

NNT

4 for functional independence (based on 28% ARR)

Effect sizes

  • OR 2.77 for favorable mRS shift (95% CI not provided in excerpt)
  • 45% vs 17% functional independence (P<0.001)

Absolute effects

  • 28% absolute increase in functional independence
  • 12% absolute reduction in mortality (14% vs 26%)

Concerns

  • Early termination limits precision
  • Confidence intervals for OR not provided in excerpt

External validity

Who it applies to

Stroke patients 6-16 hours from last known well with proximal large vessel occlusion meeting strict perfusion imaging criteria

Who it does not

Patients outside imaging selection windows, >70 ml infarct core, or without perfusion imaging capability

Generalizability notes

  • 38 US centers with pre-approved neurointerventionalists
  • Requires RAPID software or equivalent perfusion analysis

Evidence trace

Source trace and metadata

Citations (3)

claim_id

methods_critique.risk_of_bias

locator

p. 1 Methods

quote

multicenter, randomized, open-label trial, with blinded outcome assessment

claim_id

stats_check.effect_sizes

locator

p. 1 Results

quote

odds ratio, 2.77; P<0.001...45% vs. 17%, P<0.001

claim_id

practice_impact.bottom_line

locator

p. 1 Conclusions

quote

Endovascular thrombectomy...resulted in better functional outcomes than standard medical therapy alone

Metadata

Generated at

2026-03-06T13:41:29.251Z

Version

top 100 cited in past 20 years