Heterogeneity of Treatment Effects in an Analysis of Pooled Individual Patient Data From Randomized Trials of Device Closure of Patent Foramen Ovale After Stroke

Kent, DM; Saver, JL; Kasner, SE; Nelson, J; Carroll, JD; Chatellier, G; Derumeaux, G; Furlan, AJ; Herrmann, HC; Jüni, P; Kim, JS; Koethe, B; Lee, PH; Lefebvre, B; Mattle, HP; Meier, B; Reisman, M; Smalling, RW; Soendergaard, L; Song, JK; Mas, JL; Thaler, DE

doi:10.1001/jama.2021.20956

Heterogeneity of Treatment Effects in an Analysis of Pooled Individual Patient Data From Randomized Trials of Device Closure of Patent Foramen Ovale After Stroke

JAMAPublished 14 Dec 2021Pooled individual patient data analysis of randomised trials

An erratum to this article was published (JAMA, 25 Jan 2022 ↗)

Pooled result · Ischemic stroke, by RoPE Score and PASCAL category (subgroups)ResultAdjusted hazard ratio 0.41 95% CI 0.28–0.60

Read the original article ↗PubMed

Cite

Authors' conclusion

Among patients aged 18 to 60 years with PFO-associated stroke, risk reduction for recurrent stroke with device closure varied across groups classified by their probabilities that the stroke was causally related to the PFO.

Study context

Population: Patients aged 18 to 60 years with patent foramen ovale (PFO)-associated stroke; subgroups by Risk of Paradoxical Embolism (RoPE) Score and PFO-Associated Stroke Causal Likelihood (PASCAL) Classification (unlikely, possible, probable)
Participants: 3,740 patients6 RCTs

Comparison: PFO closure plus medical therapy vs medical therapy alone
Outcome: Ischemic stroke
Follow-up: Median 57 months (IQR, 24-64)

Methodological detailssubgroup analysis, 6 RCTs, heterogeneity of treatment effect analysis, SCOPE Consortium; trials conducted worldwide 2000 to 2017

Subgroup analysis
6 RCTs
Heterogeneity of treatment effect analysis
SCOPE Consortium; trials conducted worldwide 2000 to 2017

Pooled result

As reported in the abstract

Ischemic stroke, by RoPE Score and PASCAL category (subgroups)

Adjusted hazard ratio

0.41

95% CI 0.28–0.60

By group

Medical therapy1.09%annualized incidence · 95% CI 0.88%–1.36%

Device closure0.47%annualized incidence · 95% CI 0.35%–0.65%

Device closurevs Medical therapy

adjusted HR 0.41 (95% CI 0.28–0.60)

Low RoPE Score: HR, device closure vs medical therapy: 0.61 (95% CI, 0.37-1.00)
High RoPE Score: HR, device closure vs medical therapy: 0.21 (95% CI, 0.11-0.42)
RoPE Score interaction: P for interaction = 0.02
PASCAL unlikely: HR, device closure vs medical therapy: 1.14 (95% CI, 0.53-2.46)
PASCAL possible: HR, device closure vs medical therapy: 0.38 (95% CI, 0.22-0.65)
PASCAL probable: HR, device closure vs medical therapy: 0.10 (95% CI, 0.03-0.35)
PASCAL interaction: P for interaction = 0.003
PASCAL unlikely: 2-year absolute risk reduction: −0.7% (95% CI, −4.0% to 2.6%)
PASCAL possible: 2-year absolute risk reduction: 2.1% (95% CI, 0.6%-3.6%)
PASCAL probable: 2-year absolute risk reduction: 2.1% (95% CI, 0.9%-3.4%)

Further pooled results

Ischemic stroke, overall · median follow-up 57 months

Outcomes in 3740 patients: 121

Safety

AF beyond day 45 after randomization with a device, by PASCAL category

PASCAL unlikely: absolute risk increase in AF: 4.41% (95% CI, 1.02% to 7.80%)
PASCAL possible: absolute risk increase in AF: 1.53% (95% CI, 0.33% to 2.72%)
PASCAL probable: absolute risk increase in AF: 0.65% (95% CI, −0.41% to 1.71%)

Device-associated adverse events generally higher among patients classified as unlikely

Original publication

Heterogeneity of Treatment Effects in an Analysis of Pooled Individual Patient Data From Randomized Trials of Device Closure of Patent Foramen Ovale After Stroke. JAMA. Published 14 December 2021. doi:10.1001/jama.2021.20956

Read the original article ↗

Composed by AI from the published abstract and checked against it. How Briefs are made →