Ethical issues in stroke thrombolysis revisited

Appelros, Peter; Svensson, Elisabeth; Heidenreich, Kaja; Svantesson, Mia

doi:10.1111/ane.13530

Cited by 3 publications

(5 citation statements)

References 59 publications

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“…The use of thrombolytic in the 3 to 4.5 h time window is still under debate. 3,18,19 The only study designed to specifically evaluate the efficacy of tPA within 3 and 4.5 h after symptom onset (ECASS-III) found benefit (mRS score 0-1 at 90 days) and safety (symptomatic ICH or death) independent to stroke severity. 20 However, only 128 patients with an NIHSS score of 0 to 5 were included in ECASS-III.…”

Section: Discussionmentioning

confidence: 99%

Reasons and predictors of non‐thrombolysis in patients with acute ischemic stroke admitted within 4.5 h

Bergh

Jahr

Rønning

et al. 2022

Acta Neuro Scandinavica

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Objectives Thrombolytic treatment in acute ischemic stroke (AIS) reduces stroke‐related disability. Nearly 40% of all patients with AIS (<4.5 h) receive thrombolysis, but there is a large variation in the use between hospitals. Little is known about reasons and predictors for not giving thrombolytic treatment. Therefore, we aimed to investigate reasons for non‐thrombolysis in patients admitted within 4.5 h. Methods All patients with AIS (<4.5 h) admitted to Akershus University Hospital, Norway, between January 2015 and December 2017 were examined. Patient characteristics and reasons for not giving thrombolysis were registered. Descriptive statistics and logistic regression analyses were performed. Results Of 535 patients admitted with AIS (<4.5 h), 250 (47%) did not receive thrombolysis and of these only 26% had an absolute contraindication to treatment. Among the 74% with relative contraindications, the most common reasons given were mild and improving symptoms. Previous stroke (OR 3.32, 95%CI 1.99–5.52), arriving between 3 h and 4.5 h after onset (OR 7.76, 95%CI 3.73–16.11) or having mild symptoms (OR 2.33, 95%CI 1.56–3.49) were all significant predictors of not receiving thrombolytic treatment in the multivariable logistic regression model. Conclusion A large proportion of patients with AIS do not receive thrombolysis. This study highlights up‐to‐date findings that arriving late in the time window, mild symptoms, and previous stroke are strong predictors of non‐treatment. It is uncertain whether there is an underuse of thrombolysis in AIS. Increasing the utility of thrombolysis in the 4.5 h time window must be weighed against possible harms.

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Section: Discussionmentioning

confidence: 99%

Reasons and predictors of non‐thrombolysis in patients with acute ischemic stroke admitted within 4.5 h

Bergh

Jahr

Rønning

et al. 2022

Acta Neuro Scandinavica

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“…Although CCA is considered a naive imputation method, it generally over‐estimates benefit and under‐estimates harm 3 . These findings cast doubt on assumptions made that MOD are missing at random (MAR) and is consistent with prior concerns regarding excess mortality with alteplase treatment 31 …”

Section: Discussionmentioning

confidence: 63%

“…3 These findings cast doubt on assumptions made that MOD are missing at random (MAR) and is consistent with prior concerns regarding excess mortality with alteplase treatment. 31 A major difference between the neuroimaging guidance treatment meta-analysis and the chosen meta-analysis are de-facto exclusions of stroke mimics in the former. Given the marked difference in mortality and likelihood that stroke mimics contribute to survival at 90 days, stroke mimics may be an important source of attrition bias in time-based treatment meta-analyses.…”

Section: Different Methods Of Imputation Incur Different Tradeoffs In...mentioning

confidence: 99%

Methodological survey of missing outcome data in an alteplase for ischemic stroke meta‐analysis

Garg

2022

Acta Neuro Scandinavica

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Objective Recent national guidelines recommend alteplase treatment for ischemic stroke within 4.5 h of symptom‐onset based on meta‐analyses of randomized controlled clinical trials (RCT). A detailed description of missing outcome data (MOD) due to participant loss to follow‐up has never been published. The objective of this study was to perform a methodlogical survey on missing outcome data in an alteplase for ischemic stroke meta‐analysis. Materials and Methods A methodological survey was performed on a chosen meta‐analysis of alteplase for ischemic stroke RCTs that most closely aligns with recent national guideline recommendations. Data were collected to assess the number of participants lost to follow‐up; differential lost to follow‐up between allocation groups; baseline characteristics of those lost to follow‐up; and the imputation methods used by individual trials and the chosen meta‐analysis. The number of participants lost to follow‐up was compared with the fragility index; and repeated for individually positive RCTs in the meta‐analysis. Results The methodological survey revealed a substantial degree of missing information regarding MOD in the chosen meta‐analysis and in individual RCTs. Single imputation was exclusively used in all RCTs and in the meta‐analysis. The number of participants lost to follow‐up was greater than the fragility index in the chosen meta‐analysis and individually positive component RCTs suggesting that MOD may impact the direction of the reported effect or effect size. Conclusion This methodological survey of an alteplase for ischemic stroke meta‐analysis revealed MOD may be an important source of unrecognized bias. This survey highlights the need for sensitivity analyses using more robust methods of imputation.

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“…There are at least three objections to this way of reasoning. Non‐significant results are not proof of the null hypothesis; they only show that the examined material does not have sufficient power to prove the research hypothesis 4,5 Even if it could be confirmed that the increased mortality was neutralized between 7 days and 6 months, it would still mean that many patients were deprived of life days. In the Cochrane review of thrombolysis, it is clear that the reduced mortality observed between 7 and 10 days and end of follow‐up, was driven by IST‐3 only 6 .…”

mentioning

confidence: 97%

“…Non-significant results are not proof of the null hypothesis; they only show that the examined material does not have sufficient power to prove the research hypothesis. 4,5 2. Even if it could be confirmed that the increased mortality was neutralized between 7 days and 6 months, it would still mean that many patients were deprived of life days.…”

mentioning

confidence: 99%