How can we improve stroke thrombolysis rates? A review of health system factors and approaches associated with thrombolysis administration rates in acute stroke care

Stroke causes five million deaths worldwide [1, 2] with escalating costs to the health system [3‐6]. Most stroke cases (89 %) are admitted to hospital [7], with approximately 50 % of sufferers left deceased or dependent [8]. Thrombolysis using intravenous (IV) tissue plasminogen activator (tPA) is one of the few evidence-based acute stroke treatments [9, 10].

Despite the potential benefit offered by routine delivery of thrombolysis to eligible stroke patients, achieving and sustaining high rates of IV tPA delivery has been problematic.

While seeking treatment late is a major limiting factor on tPA delivery [11, 12], health system factors (i.e. circumstances that are determined by the health organisation or the health care provider rather than the individual) are important in improving access to thrombolysis for stroke patients. While there is no agreed benchmark for rates or levels of thrombolysis in practice, substantial change has been shown to be achievable such as an increase in tPA administration rate from 4.7 to 21.4 % of all stroke patients [13].

The narrow treatment window of 4.5 h from stroke onset, negative impacts of inappropriate treatment, along with the multi-step, multi-disciplinary testing, and decision-making process needed to determine thrombolysis eligibility would indicate that complex interventions are required to change thrombolysis rates [14]. Complex interventions are generally defined as those which involve a number of interacting components, require a number of behaviours or difficult behaviours, involve a number of groups or organisational levels and have a number of outcomes [14], each of which is directly relevant to thrombolysis for acute stroke. Barriers to treatment include delays in stroke recognition by staff [15], delays in obtaining and interpreting radiology imaging [16], inefficiencies in emergency stroke care and delays in obtaining treatment consent [17].

Study of the diffusion of new technologies indicates that while some innovations are largely adopted in less than 5 years [18], others may fail to become commonplace due to barriers or failures at a higher level [19]. In these contexts, the use of theoretical frameworks such as the Behaviour Change Wheel (BCW) [20] can be helpful to clarify the range of factors which may need to be addressed in order to effect change. The BCW describes the three essential conditions for behaviour change to occur: capability, opportunity and motivation; nine intervention functions and seven policy categories are required for whole system change [20]. Models and frameworks such as the BCW emphasise the importance of intervening not only at the level of the individual but also at an organisational or system level and at the broader policy level. While policy-level factors such as financial incentives may impact on thrombolysis over the long term [21], in the short to medium term, health service providers may have the greatest potential impact by acting at a health system or organisational level.

A number of cross-sectional studies have described associations between higher stroke tPA rates and system-level factors such as hospital size and hospital type [22, 23] or characteristics such as staffing [24] or stroke certification [25‐28]. System-level approaches have been recommended to improve access to IV tPA and increase the proportion of patients receiving the treatment, including telemedicine and centralised hub and spoke models [29‐31]. Some studies have described successful attempts to apply hospital pre-notification systems [13] or quality-improvement approaches (e.g. analysing performance, with systematic efforts to improve it, ultimately resulting in better health outcomes) [32, 33], to increase tPA implementation for stroke.

However, system changes require substantial resources and engagement with quality improvement programmes. To our knowledge, there are no published reviews of a broad range of evidence-based health system factors associated with increased IV tPA administration rates for stroke.

The search resulted in 4323 citations (MEDLINE n = 1947, EMBASE n = 1760, PsycINFO n = 46, CINAHL n = 570). As indicated in Fig. 1, 34 studies reported associations between health system factors and IV tPA rates for ischemic stroke. Seven intervention studies that reported an improvement in IV tPA rates met the EPOC design criteria. Forty-seven intervention studies were excluded as being either pre-test-post-test designs with no control group or pilot tests with post-test only data. The types of intervention strategies studied in the 47 excluded publications included the following: the introduction of stroke units or “code-stroke” protocols; support for regional sites (e.g. hub and spoke models, telemedicine); changes in hospital protocols, staffing or rostering; and the “Get With The Guidelines” programme [37].

This systematic review brings together the empirical evidence regarding potential strategies for improving thrombolysis rates for acute stroke. The review data provide a basis on which stroke service providers can identify which strategies are more likely to be good investments for increasing rates of thrombolysis. As per the literature regarding complex interventions [14] and frameworks such as the BCW [20], a range of strategies or factors are related to achieving change in thrombolysis rates. Of note is that the literature only addresses three of the nine intervention functions and two of the seven policy categories raised in the BCW framework, suggesting a much wider range of strategies could be tested in the future.

A small number of system-related factors are associated with higher rates of IV tPA administration for ischemic stroke. Systems-change interventions, based on multi-component quality improvement approaches, can increase the proportion of eligible stroke patients receiving IV tPA.

The observational literature regarding factors associated with higher stroke tPA rates was heterogeneous in methodology and types of factors assessed, but it is unclear whether each study had sufficient power to detect an association for each factor. The literature indicates that health systems should aim to ensure that most stroke patients are treated in a way that minimises access disadvantages for rural populations; maximises access to neurological and stroke-specific expertise and experience; ensures stroke units are widely available; and implements stroke-specific protocols. The association of higher IV tPA rates with treatment at a teaching hospital or a hospital with larger stroke or IV tPA treatment volume suggests that expertise and experience within such settings is key to increased IV tPA rates. The mixed findings regarding the importance of treatment at a larger hospital and arrival during “on” hours or weekends indicate that greater size and availability of staff alone do not produce higher IV tPA rates. However, it must be noted that observational studies cannot be used to draw definitive conclusions regarding causation. The observational studies were also largely retrospective in design and had limited capacity to identify and assess confounding factors. Therefore, a greater focus must be directed towards the data from the experimental or intervention studies.

Organisational elements such as stroke certification and quality improvement activities were not associated with higher IV tPA rates. One study [25] failed to find an association between facilities, staffing and organisational elements and quality improvement outcomes or activities. These elements are often the focus of system-change interventions and can be resource intensive to implement. Therefore, robust experimental studies are essential to providing clarity about cost-effective approaches to improved IV tPA rates. Organisational elements such as stroke-related certification or time on the Get With The Guidelines programme did not increase IV tPA rates.

The intervention studies suggest that while quality-improvement or system-change interventions can be effective in increasing IV tPA rates, studies are heterogeneous and effects may be small or inconsistent. The PRACTISE trial [41] found a positive effect on IV tPA rates and patient functioning following a Breakthrough Series intervention. The INSTINCT trial [43] reported a positive effect only when the analysis focussed on a subset of study sites. The INSTINCT intervention placed less emphasis on collaborative meetings compared to the PRACTISE trial but included stroke champions, education/support for treatment decision making and performance feedback [43]. The Morgenstern et al. study [42] identified a greater increase in IV tPA rates in intervention sites, compared to control sites.

This study [42] differed from the two other studies by including community-focussed mass media. It also included hospital-based change via multi-disciplinary teams, development of emergency department protocols, problem solving, medical education and performance feedback. Given the small number of hospitals involved, the choice of patient rather than hospital as the unit of analysis, and the lack of any head-to-head analysis across groups, some caution should be applied to interpreting the results of the Morgenstern et al. study [42].

Other studies support the finding that quality improvement strategies can provide modest positive effects on other aspects of stroke care [32, 44, 45]. The “Stroke 90:10” trial found an 11 % relative improvement in some aspects of initial assessment and care for stroke patients following collaborative quality improvement [45]. Another study involving workshops, education, site-based teams, performance feedback and decisional support suggests that improvements in thrombolysis occurred over time [32]. While the study could be classified as an interrupted time series based on quarterly measurements over 4 years, the analysis did not follow usual approaches to analysing time-series data. Although the cost of IV tPA administration was not addressed in the reviewed studies, the scope of multi-component, multi-site interventions suggests the resources required are substantial.

Two studies [38, 39] compared telemedicine with a telephone-only approach, focusing on environmental restructuring rather than quality improvement to increase IV tPA delivery. Conclusions are difficult to make, as neither study indicated sufficient power to detect a difference in IV tPA rates. The study of tele-consultation compared to usual care [40] suggested, but did not conclusively demonstrate, patient outcome benefits, given a failure to statistically examine experimental versus control site outcomes. A later pooled analysis confirmed telemedicine consultations were not associated with increased thrombolysis rates [46]. While these changes may increase access to expert care, they lack robust evidence.

Observational and intervention data suggest that optimising IV tPA administration requires availability of expertise and protocols. Intervention studies suggest more in-depth reporting of the degree to which various intervention strategies may assist in understanding the best way forward. While multi-component approaches appear promising, two important questions emerge:

The broader context is also important to consider, such as the financial incentives to hospitals for or against thrombolysis delivery in certain settings [21]. Adapting system thinking where components of the health system are dynamic and interlinked may assist in further understanding the network of relations and feedback loops impacting on the uptake of new innovations [47]. It may also be useful to develop a broader theoretical framework that could be applied to future studies in this area.

Limitations should be considered when interpreting the study tables: firstly, the reported rates of IV tPA (see Table 2) are dependent on denominator and eligibility criteria, which can affect the power of the study to detect a difference in the outcome; secondly, the variability in factors explored across studies of descriptive health system factors limits the ability to make comparisons among studies; and finally, the nature of changing care at a system level limits design rigour such as the ability to blind sites to group allocation. As a “Google” search was not used, a small number of unpublished studies may not have been identified.

Access to teaching hospitals and hospitals with larger stroke and IV tPA treatment volumes is associated with increased IV tPA administration rates for stroke, although results should be viewed against variability in eligibility criteria and type of denominator used. Interventions aiming to increase rates of IV tPA are resource intensive and comparisons between studies are difficult due to insufficient power and limitations in study analysis. More empirical data regarding the effects of efforts to improve access to thrombolysis for those living long distances (e.g. mobile thrombolysis) from a tPA-capable hospital and 24-h availability of expertise in acute stroke care are required, as is more thoughtfully designed and well-reported trials of quality improvement interventions.