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. 2014 May 30:348:g3429.
doi: 10.1136/bmj.g3429.

Time to treatment with recombinant tissue plasminogen activator and outcome of stroke in clinical practice: retrospective analysis of hospital quality assurance data with comparison with results from randomised clinical trials

Christoph Gumbinger  1 , Björn Reuter  2 , Christian Stock  3 , Tamara Sauer  2 , Horst Wiethölter  4 , Ingo Bruder  5 , Susanne Rode  5 , Rolf Kern  2 , Peter Ringleb  1 , Michael G Hennerici  2 , Werner Hacke  6 ; AG Schlaganfall
Collaborators, Affiliations

Time to treatment with recombinant tissue plasminogen activator and outcome of stroke in clinical practice: retrospective analysis of hospital quality assurance data with comparison with results from randomised clinical trials

Christoph Gumbinger et al. BMJ. .

Abstract

Objective: To study the time dependent effectiveness of thrombolytic therapy for acute ischaemic stroke in daily clinical practice.

Design: A retrospective cohort study using data from a large scale, comprehensive population based state-wide stroke registry in Germany.

Setting: All 148 hospitals involved in acute stroke care in a large state in southwest Germany with 10.4 million inhabitants.

Participants: Data from 84,439 patients with acute ischaemic stroke were analysed, 10,263 (12%) were treated with thrombolytic therapy and 74,176 (88%) were not treated.

Main outcome measures: Primary endpoint was the dichotomised score on a modified Rankin scale at discharge ("favourable outcome" score 0 or 1 or "unfavourable outcome" score 2-6) analysed by binary logistic regression. Patients treated with recombinant tissue plasminogen activator (rtPA) were categorised according to time from onset of stroke to treatment. Analogous analyses were conducted for the association between rtPA treatment of stroke and in-hospital mortality. As a co-primary endpoint the chance of a lower modified Rankin scale score at discharge was analysed by ordinal logistic regression analysis (shift analysis).

Results: After adjustment for characteristics of patients, hospitals, and treatment, rtPA was associated with better outcome in a time dependent pattern. The number needed to treat ranged from 4.5 (within first 1.5 hours after onset; odds ratio 2.49) to 18.0 (up to 4.5 hours; odds ratio 1.26), while mortality did not vary up to 4.5 hours. Patients treated with rtPA beyond 4.5 hours (including mismatch based approaches) showed a significantly better outcome only in dichotomised analysis (odds ratio 1.25, 95% confidence interval 1.01 to 1.55) but the mortality risk was higher (1.45, 1.08 to 1.92).

Conclusion: The effectiveness of thrombolytic therapy in daily clinical practice might be comparable with the effectiveness shown in randomised clinical trials and pooled analysis. Early treatment was associated with favourable outcome in daily clinical practice, which underlines the importance of speeding up the process for thrombolytic therapy in hospital and before admission to achieve shorter time from door to needle and from onset to treatment for thrombolytic therapy.

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Conflict of interest statement

Competing interest: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: CG holds a scholarship from the Nachwuchsakademie Versorgungsforschung (a health service research body) for a programme in Baden-Wuerttemberg. RK received speaker’s honorariums from Boehringer Ingelheim, Pfitzer, and Philips Healthcare, and received funding from the Federal Ministry of Education and Research (BMBF), Germany. He is a member of the editorial board of the journal Cerebrovascular Diseases. IB is the project leader at GeQiK. PR is the national coordinator of the SITS-registry and has received lecture fees and travel compensation for talks regarding thrombolysis and acute stroke treatment from Boehringer-Ingelheim, Ferrer, Paion, Bayer, Sanofi. MGH was the first chair of the Stroke Quality Assurance Committee and the lead author of the quality assessment questionnaire. WH was the first chair of the stroke unit working group in the state of Baden-Wuerttemberg and initiated the SU certification process. He was the chair of the stroke unit working group when the quality assessment was started. He was also the chair of the ECASS 1-3 studies and was compensated for his time by Boehringer Ingelheim, for which he is a consultant.

Figures

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Fig 1 Flow chart of inclusion of patients in study of treatment with recombinant tissue plasminogen activator and outcome of stroke in clinical practice
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Fig 2 Odds ratio for favourable outcome (score 0-1 on modified Rankin scale) with time to treatment with recombinant tissue plasminogen activator after onset of stroke in binary logistic regression analysis and comparisons with trials (pooled analysis of randomised clinical trials of alteplase for acute stroke4)
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Fig 3 Odds ratios for lower score on modified Rankin scale with time to treatment with recombinant tissue plasminogen activator after onset of stroke in ordinal logistic regression analysis
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Fig 4 Odds ratio for mortality with time to treatment with recombinant tissue plasminogen activator after onset of stroke and comparisons with pooled analysis of randomised clinical trials of alteplase for acute stroke
See this image and copyright information in PMC

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