|Intravenous thrombolysis in stroke patients of >=80 versus <80 years of age: a systematic review across cohort studies
|Engelter S T, Bonati L H, Lyrer P A
This review, which compared the benefits and risks of intravenous recombinant tissue plasminogen activator in stroke patients aged 80 years and older with patients younger than 80 years, concluded that the risk of mortality is substantially higher for older patients. Given several limitations relating to the methodology and quality of the included studies, the reliability of the authors' conclusions is unclear.
To evaluate the benefits and risks of intravenous recombinant tissue plasminogen activator (rtPA) in stroke patients.
MEDLINE (via PubMed; 1966 to July 2006) and the Science Citation Index (to July 2006) were searched; the search terms were reported. In addition, citations from retrieved articles were reviewed.
Cohort studies comparing the use of intravenous rtPA in stroke patients aged 80 years and older (older group) with control patients younger than 80 years (younger group) were eligible for inclusion. Case reports and case series with a historical control were excluded. Studies were eligible for inclusion if they reported one of the following as the primary outcome: mortality, functional outcome measured with the modified Rankin Scale (mRS) score after 3 months, and symptomatic intracranial haemorrhage (sICH) according to reported definitions. The included studies were of patients with various conditions, such as ischaemic or congestive heart disease, cardioembolic stroke aetiology, atrial fibrillation, a history of congestive heart failure, and hyperlipidaemia. There was a greater number of participants in the younger age group and a higher proportion of females, and ages ranged from 23 to 97 years. The included studies reported in-hospital or 3-month mortality, discharge mRS or mRS after 3 months, ICH, recanalisation, or predictors of outcome complications. ICH was defined as computed tomography/magnetic resonance imaging (CT/MRI)-documented haemorrhage temporally related to any deterioration in the patient's clinical condition, or as any intracerebral blood on follow-up CT/MRI, associated with an increase in National Institutes of Health Stroke Scale Score of at least 4 points.
The authors did not state how the papers were selected for the review, or how many reviewers performed the selection.
Assessment of study quality
One reviewer assessed validity according to a modified version of a published 12-criteria checklist.
Data on all-cause mortality (approximately 3 months post-stroke) and favourable outcome (defined as an mRS score of 1 or less after 3 months, for all patients, survivors and patients with sICH) were extracted. Ultimately, to calculate weighted estimates of the odds ratios (ORs) with 95% confidence intervals (CIs).
Two reviewers independently extracted the data and any disagreements were resolved through consensus.
Methods of synthesis
The ORs were pooled for each outcome using a Peto fixed-effect model or a random-effects model, where appropriate.
Subgroup analyses were carried out by age group and sensitivity analyses were conducted by removing the lowest quality study. Statistical heterogeneity was assessed using the χ2 test.
Results of the review
Six cohort studies (n=2,244: n=477 older group, n=1,767 younger group) were included in the review. Sample sizes ranged from 30 to 865 participants.
The included studies scored between 6 and 9 out of 12 in the methodological assessment.
Patients in the older group had a higher mortality risk compared with the younger group (OR 3.09, 95% CI: 2.37, 4.03, p<0.001). Based on four studies, there was a significant difference in recovery, this being less favourable for the older group overall (OR 0.53, 95% CI: 0.42, 0.66, p<0.001) and for survivors among the older group (OR 0.69, 95% CI: 0.53, 0.90, p=0.007). There was no statistically significant difference in sICH between the two groups. Sensitivity analyses did not significantly alter the results for mortality or sICH.
Statistical heterogeneity was reported as mild (I2=10.8%) for definitions of sICH.
Treatment with intravenous rtPA has less favourable outcomes in older stroke patients than in younger ones. However, compared with younger stroke patients, older patients do not seem exceedingly prone to sICH and may therefore benefit from thrombolysis.
The review question was clear and supported by appropriate inclusion criteria for the participants, interventions, outcomes and study design. The literature search was quite limited, using only two electronic databases and other appropriate sources, and it was not clear whether any language restrictions were applied; publication and language bias cannot, therefore, be ruled out. Together with the fact that there was no apparent search for unpublished material, it is possible that relevant papers were missed. Details of the validity assessment and data extraction were provided, but not of the screening process, thus the potential for reviewer error and bias at this stage cannot be ruled out. Although some assessment of statistical heterogeneity was reported, there were differences in the baseline characteristics of the patients and the methodology and quality of the studies. Furthermore, CIs were wide for some of the outcomes and sample sizes were small, which means that the reliability of the subsequent synthesis is unclear. Although the authors appear to have considered such limitations, the reliability of their conclusions is unclear.
Implications of the review for practice and research
Practice: The authors stated that the findings should not be interpreted as evidence for or against a beneficial effect of intravenous rtPA for older stroke patients as all patients received rtPA.
Research: The authors stated that it is safe and reasonable to include stroke patients aged 80 years and older in randomised placebo-controlled trials assessing the risk and benefit of intravenous rtPA.
Basel 'Hirnschlag [Stroke] Fonds'.
Engelter S T, Bonati L H, Lyrer P A. Intravenous thrombolysis in stroke patients of >=80 versus <80 years of age: a systematic review across cohort studies. Age and Ageing 2006; 35(6): 572-580
Subject indexing assigned by NLM
Age Factors; Aged; Aged, 80 and over; Cohort Studies; Fibrinolytic Agents /therapeutic use; Humans; Recombinant Proteins /therapeutic use; Stroke /drug therapy; Thrombolytic Therapy /methods; Tissue Plasminogen Activator /therapeutic use; Treatment Outcome
Database entry date
This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.