Safety and efficacy of IV-TPA for ischaemic stroke in clinical practice--a Bayesian analysis.
BACKGROUND
Observational studies of new treatments in routine practice are clinically important but may be limited by bias. We used a Bayesian approach to interpret and sequentially combine phase 4 studies of IV-TPA within 3 h for acute ischaemic stroke to quantify the cumulative evidence for the efficacy and safety of this therapy in clinical practice.


METHODS
Prior probability distributions for favourable outcome (modified Rankin Score, mRS, 0-1), symptomatic intracerebral haemorrhage, and mortality 3 months after IV-TPA were derived from the NINDS trial. Phase 4 studies from observational case series and from regulator-mandated large registries were included. A cumulative analysis was performed to quantify the increase in the total evidence base over time, unadjusted and adjusted for potential bias.


RESULTS
The cumulative analysis indicated that IV-TPA <3 h was associated with 3-month favourable outcome in 37.1% (95% credible interval, CrI, 36.1-38.0%, n = 9,578) compared to 26% (95% confidence interval, CI, 19.6-32.9%, n = 165) in placebo-treated patients in NINDS, symptomatic intracranial haemorrhage in 6.6% (95% CrI 5.9-7.4%, n = 10, 834) compared to 6.4% (95% CI 4.0-9.4%) in the NINDS IV-TPA group, and 3-month mortality in 13.6% (95% CrI 12.6-14.8%, n = 9, 901) compared to 20.5% (95% CI 16.0-25.0%, n = 312) in the NINDS placebo group.


CONCLUSIONS
A Bayesian approach provides further confirmatory evidence of the efficacy and safety of IV-TPA for treatment of acute ischaemic stroke within 3 h in diverse clinical practice settings, after adjusting for potential observational bias.
O'Rourke
Killian E T
KE
Stroke Service, Department of Neurology, and Neurovascular Clinical Science Unit, Mater University Hospital and University College Dublin, 1 Nelson Street, Dublin 7, Ireland. killian.orourke@gmail.com
Walsh
Cathal D
CD
Kelly
Peter J
PJ
D000368:Aged; D001499:Bayes Theorem; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D055825:National Institute of Neurological Disorders and Stroke (U.S.); D011446:Prospective Studies; D012042:Registries; D020521:Stroke / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014481:United States
D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator