Benedikt Frank

Thrombolysis in Stroke Despite Contraindications or Warnings

Background and Purpose— Intravenous thrombolysis with alteplase is approved for acute ischemic stroke, but its use is limited by numerous contraindications and warnings arising from trial selection criteria or expert opinions. We examined outcomes from alteplase-treated versus untreated patients, registered in a trials archive, according to presence or absence of specified contraindications and warnings. Methods— We analyzed 90-day modified Rankin Scale across the whole distribution of scores using the Cochran–Mantel–Haenszel test, with adjustment for age and baseline National Institutes of Health Stroke Score, followed by proportional odds logistic regression analysis to estimate the odds ratios for preferred outcome. Results— We used data from 9613 ischemic stroke patients of whom 2755 were treated with thrombolysis. Adjusted odds ratios showed a broad trend of more favorable 3-month outcome associated with alteplase treatment versus no treatment in various subgroups of patients with contraindications and warnings; for example, 1.40 (95% confidence interval [CI], 1.14–1.70) in patients aged >80 (n=1805), 1.50 (95% CI, 1.03–2.18) in patients with combined history of prior stroke and diabetes mellitus (n=672), 1.42 (95% CI, 1.19–1.70) in patients on prior single antiplatelet agent (n=1626), 2.20 (95% CI, 1.12–4.32) in patients on oral anticoagulation, and International Normalized Ratio⩽1.7 (n=157), 1.50 (95% CI, 1.15–1.97) in patients with baseline glucose >180 (n=879), and 1.57 (95% CI, 1.12–2.18) in patients with pretreatment National Institutes of Health Stroke Score >22 (n=620). Conclusions— This comprehensive retrospective analysis of various contraindications and warnings provides reassurance about benefits and risks of intravenous alteplase treatment in common clinical situations.

Association of improved outcome in acute ischaemic stroke patients with atrial fibrillation who receive early antithrombotic therapy: analysis from VISTA.

Ischaemic stroke patients with atrial fibrillation (AF) are at risk of early recurrent stroke (RS). However, antithrombotics commenced at the acute stage may exacerbate haemorrhagic transformation, provoking symptomatic intracerebral haemorrhage (SICH). The relevance of antithrombotics on the patterns and outcome of the cohort was investigated.

Impact of Atrial Fibrillation on Outcome in Thrombolyzed Patients With Stroke: Evidence From the Virtual International Stroke Trials Archive (VISTA)

Background and Purpose— Atrial fibrillation has been considered a risk factor for poor outcome from acute stroke and may influence response to thrombolysis, although supporting data are limited due to potential confounding with age and stroke severity. Method— We assessed the association of atrial fibrillation and thrombolysis exposure with the modified Rankin Scale score distribution at 90 days among patients registered in a trials archive. We used an age and baseline National Institutes of Health Stroke Scale-adjusted Cochran-Mantel-Haenszel test to test significance (P) followed by proportional odds logistic regression analysis to estimate the ORs for improved modified Rankin Scale score. Results— Data were available for 7091 patients, of whom 3027 were thrombolyzed. A total of 1631 patients had a history of atrial fibrillation, of whom 639 were thrombolyzed. Among patients with atrial fibrillation, baseline severity was greater (median baseline National Institutes of Health Stroke Scale, 14 versus 12; P<0.001) and age was higher (mean age, 74.0 versus 66.5; P<0.001). An association of treatment with outcome was seen independently and was of similar magnitude within patients with atrial fibrillation (OR, 1.44; 95% CI, 1.12–1.73; P<0.001) and without atrial fibrillation (OR, 1.53; 95% CI, 1.39–1.69; P<0.001). No association of atrial fibrillation and overall stroke outcome could be found (OR, 0.93; 95% CI, 0.84–1.03; P=0.409). Conclusion— In this nonrandomized comparison, presence of atrial fibrillation had no independent impact on stroke outcome and compared with untreated comparators, the patients who received thrombolysis experienced an advantage in outcomes that was of equal magnitude whether in the presence or absence of atrial fibrillation.

Associations of chronic heart failure with outcome in acute ischaemic stroke patients who received systemic thrombolysis: Analysis from VISTA

There are concerns that systemic thrombolysis might not achieve clinically important outcome amongst chronic heart failure (CHF) patients with acute ischaemic stroke. Our aim was to investigate the relevance of CHF on the outcome of acute stroke patients who received thrombolysis.

Interdependence of Stroke Outcome Scales: Reliable Estimates from the Virtual International Stroke Trials Archive (VISTA)

Background and Purpose Clinical deficits from stroke are diverse, prompting measurement in trials by a range of outcome scales. Statistical and clinical advantage can be gained by combining scales into a global outcome provided combinations are chosen with limited correlations. We aimed to clarify the interdependence of outcome scales by systematic review of published data and by novel analysis of data from completed acute trials. Summary of Review We systematically searched ScienceDirect and PubMed to summarize published data on correlations between stroke outcome scales. We generated new data on correlations among salient scales at 90 days poststroke in patients from the Virtual International Stroke Trials Archive (VISTA). We calculated Pearson and Spearman-Rank correlation coefficients for continuous and ordinal measures, respectively. We also assessed partial correlations, adjusted for baseline National Institute of Health Stroke Scale (NIHSS), and age. Published estimates of interdependence were limited to small single-trial cohorts and gave divergent results. From the more extensive VISTA dataset, we found that the modified Rankin Scale at 90 days poststroke explained 80.8% of the National Institute of Health Stroke Scale at 90 days poststroke and 86·5% of the European Stroke Scale. National Institute of Health Stroke Scale explained 75.9% of the Barthel Index and 81·2% of the Scandinavian Stroke Scale. After adjustment, modified Rankin Scale explained 56.6% of National Institute of Health Stroke Scale, 75.2% of Barthel Index. National Institute of Health Stroke Scale explained 60.2% of Barthel Index. Conclusion Correlations and partial correlations among stroke outcome scales in trial datasets are higher than previously reported. The new estimates are more reliable for trial planning due to the sample size and diversity.

The effect of time to treatment on outcome in very elderly thrombolysed stroke patients

Background Intravenous thrombolysis is beneficial in, even very elderly, acute ischemic stroke patients. However, while the relation between treatment benefit and treatment delay (onset time to treatment) in patients younger than 80 years is well known, it is uncertain in the very elderly. Aims This analysis aims at examining this relationship in the elderly, and to provide a comparison with the derived relationship in younger patients as a check of validity. Methods We assessed the interaction between age, onset time to treatment, and thrombolysis exposure by analyzing the modified Rankin scale score distribution or mortality rate at 90 days, among patients registered in a trials archive. We established whether the effect of alteplase changes with onset time to treatment, by treating onset time to treatment as a continuum in a multivariate logistic regression model. Results Data were available for 3063 patients, of whom 2341 were thrombolysed. Five hundred ninety-seven patients were aged >80, of whom 352 were thrombolysed. Among patients aged >80, no significant interaction of outcome with onset time to treatment was observed (P = 0·4650), but the estimated slope of the decay in benefit with onset time to treatment was comparable with that established for younger patients. Analyzing the entire dataset, there was an interaction between onset time to treatment and alteplase treatment (P = 0·0159), but neither between age and onset time to treatment (P = 0·7098) nor between age and alteplase treatment (P = 0·0755). Conclusions In this nonrandomized comparison, the relationship of benefit and safety with thrombolysis across onset time to treatment in very elderly stroke patients was comparable with that in their younger counterparts. Across the investigated time span of 3·5 h, we can safely treat with the same time window as we use for younger patients.

Stroke: Stroke prevention—time to say goodbye to the ABCD2 score?

The ABCD2 score was developed to triage patients with transient ischaemic attack according to the risk of experiencing a stroke in the next few hours or days. However, a new systematic review and meta-analysis on the ABCD2 score gives us considerable cause to rethink its value for clinical situations.

Impact of benzodiazepines on functional outcome and occurrence of pneumonia in stroke: evidence from VISTA

Background Benzodiazepines have been proposed both as a neuroprotectant and risk factor for pneumonia in acute stroke. Aims We assessed the impact of benzodiazepine exposure on the modified Rankin scale score distribution at 90 days as well as pneumonia rates among patients registered in a trials archive. Method We used an age, baseline National Institutes of Health Stroke Score, and thrombolysis-rate adjusted Cochran–Mantel–Haenszel test to test significance (P) followed by proportional odds logistic regression analysis to estimate the odds ratios for improved modified Rankin scale score, and binary logistic regression to estimate the odds ratio for developing pneumonia. Results Data were available for 5938 patients, of whom 1800 received benzodiazepines. No association of benzodiazepine use and overall stroke outcome could be found (odds ratio 0·90, 95% confidence interval 0·82–1·00, P = 0·121). Pneumonia occurred in 12·8% of patients treated with benzodiazepines and in 13·6% of the controls (odds ratio 0·99, 95% confidence interval 0·83–1·18, P = 0·904). Conclusion In this nonrandomized comparison, treatment with benzodiazepines as a concomitant medication had no independent impact on stroke outcome.

Use of paracetamol in ischaemic stroke patients: evidence from VISTA

Paracetamol is frequently prescribed for pain and fever control in acute stroke patients, but its effect on stroke outcome is unclear. The aim was to investigate the safety and benefit of paracetamol administration in the acute phase of ischaemic stroke.

New anticoagulants for stroke prevention in atrial fibrillation

ZusammenfassungPatienten mit Vorhofflimmern haben ein hohes Schlaganfallrisiko. Dieses Risiko kann durch Vitamin-K-Antagonisten wie Phenprocoumon oder Warfarin sowohl in der Primär- als auch in der Sekundärprävention, verglichen mit Placebo, um 60–70% reduziert werden. Vitamin-K-Antagonisten haben allerdings eine Vielzahl von Problemen in der praktischen Anwendung, was die relativ geringe Einnahmefrequenz bei Patienten mit Vorhofflimmern erklärt. Neue orale Antikoagulanzien wie direkte Thrombininhibitoren (Dabigatran) oder direkte Faktor-Xa-Hemmer wie Rivaroxaban und Apixaban zeigten eine im Vergleich zu Warfarin mindestens ebenbürtige wenn nicht höhere Wirksamkeit und zum Teil auch eine niedrigere Inzidenz an schwerwiegenden Blutungskomplikationen. Die neuen Substanzen sind sowohl in der Sekundär- als auch in der Primärprävention von Schlaganfällen bei Patienten mit Vorhofflimmern wirksam. Apixaban ist auch deutlich wirksamer als Azetylsalizylsäure bei Patienten, die für eine Behandlung mit Warfarin nicht geeignet sind, bei vergleichbarer Rate an schwerwiegenden Blutungskomplikationen.AbstractOral anticoagulation with vitamin K antagonists (warfarin, phenprocoumon) is successful in both primary and secondary stroke prevention for patients with atrial fibrillation (AF), yielding a 60–70% relative reduction in stroke risk compared with placebo and a mortality reduction of 26%. However, these agents have a number of well documented shortcomings. This review describes the current landscape and developments in stroke prevention in patients with AF with special reference to secondary prevention. A number of new drugs for oral anticoagulation that do not exhibit the limitations of vitamin K antagonists are under investigation. These include direct factor Xa inhibitors and direct thrombin inhibitors. Recent studies (RE-LY, ROCKET-AF, AVERROES, ARISTOTLE) provide promising results for these new agents including higher efficacy and significantly lower incidences of intracranial bleeding compared with warfarin. The new substances show similar results in secondary as well as in primary stroke prevention in patients with AF. The new anticoagulants add to the therapeutic options for patients with AF and offer a number of advantages over warfarin for both clinician and patient, including a favorable bleeding profile and convenience of use. Consideration of these new anticoagulants will improve clinical decision-making.Oral anticoagulation with vitamin K antagonists (warfarin, phenprocoumon) is successful in both primary and secondary stroke prevention for patients with atrial fibrillation (AF), yielding a 60-70% relative reduction in stroke risk compared with placebo and a mortality reduction of 26%. However, these agents have a number of well documented shortcomings. This review describes the current landscape and developments in stroke prevention in patients with AF with special reference to secondary prevention. A number of new drugs for oral anticoagulation that do not exhibit the limitations of vitamin K antagonists are under investigation. These include direct factor Xa inhibitors and direct thrombin inhibitors. Recent studies (RE-LY, ROCKET-AF, AVERROES, ARISTOTLE) provide promising results for these new agents including higher efficacy and significantly lower incidences of intracranial bleeding compared with warfarin. The new substances show similar results in secondary as well as in primary stroke prevention in patients with AF. The new anticoagulants add to the therapeutic options for patients with AF and offer a number of advantages over warfarin for both clinician and patient, including a favorable bleeding profile and convenience of use. Consideration of these new anticoagulants will improve clinical decision-making.