Discussion

Several clinical trials have recently shown the benefit of endovascular reperfusion therapy compared with medical therapy in patients with large vessel occlusive disease.10–12 There has been increased recognition of the importance of door to needle times for intravenous tissue plasminogen activator, with a focus on reducing these times and increasing delivery rates in order to improve clinical outcomes.13 Similarly, the American Heart Association has proposed an ‘arrival to treatment’ time of <2 h for patients undergoing endovascular stroke therapy.14 The current study shows that the majority of highly experienced centers participating in clinical trials and registries do not achieve this metric. Moreover, despite improving procedure and hospital arrival to puncture times (door to puncture), there does not appear to be a concordant improvement in the last known normal to puncture times which is strongly correlated with neurological outcomes at 90 days. It interesting to note that in the last quarter of 2010 there was a last known normal to treatment time of <180 min with a good outcome rate of nearly 60%. Although there may be alternative explanations for this high rate of good outcome, the time component is likely to be contributory.

Endovascular reperfusion therapies have continued to evolve over the past decade. New devices have been introduced with the promise of improving reperfusion rates in an expeditious manner. These efforts, along with increasing operator experience, appear to be making an impact. Our results show a decrease of roughly 40 min or 30% between 2003 and 2011, and other studies have reported similar reductions in procedure times.15–17 Yet neurological outcomes have not improved in a similar fashion. This is probably due to the fact that the procedure length accounts for a relatively small proportion of the time interval from symptom onset to successful reperfusion. It is estimated that almost 75% of the occlusion time precedes the start of intra-arterial treatment in the care of the patient and, as we have shown, pre-procedure times have not changed in the last decade.3 This stresses the importance of process improvement for the workflow leading up to the interventional suite. It is important to note that patients treated beyond 9 h were excluded from this analysis and the reason for the lack of improvement cannot be attributed to selecting patients with later onset strokes only.

In thinking about process improvement, it is helpful to break down the pre-procedure time interval around the time of patient arrival at the treating facility. The problems related to pre-arrival delay are distinct from those accounting for in-hospital delays to the interventional suite. With respect to in-hospital delays, there have been few efforts to systematically improve door to puncture times for intra-arterial therapy. This is in contrast to the major initiatives that seek to reduce door to needle times in the delivery of intravenous tissue plasminogen activator for eligible patients. The Target Stroke Initiative is working towards a goal door to needle time of <60 min.18 The aim of this initiative is for 50% of patients to be treated within this time frame.

The recent analysis of the Interventional Management of Stroke III study showed the mean time from symptom onset to reperfusion was 325 min.15 Roughly 45% of the delay (146 min) is attributed to the time from arrival at the emergency room to groin puncture (door to puncture).16 This is similar to our finding in the current analysis of 162±78 min for the overall cohort. It is interesting to note that there was a significant improvement in the door to puncture time in 2011 to 120±66 min, similar to that reported in a recent registry from patients enrolled in 2012 where the median door to puncture time was 112 min.5 This improvement may reflect the recent emphasis on the speed of intra-arterial treatment delivery, although this finding needs to be verified in other datasets.

A frequently cited delay that occurs within the hospital is the time spent obtaining advanced modality imaging at the treatment facility.2 ,19 The addition of imaging such as MRI and CT perfusion may lead to delays in the pre-endovascular treatment of the patient and may be more prevalent than in the earlier period of this study. Unfortunately, we do not have access to the timings and rates of advanced modality imaging in this cohort. More data are needed to determine whether the additional information obtained from this imaging is worth the time spent in acquiring and interpreting it.

With respect to pre-arrival delay, valuable time is lost when patients are transferred from a non-interventional to an interventional center. In a recent analysis, transferred patients had a last known normal to puncture time of 301 min compared with 177 min for non-transferred patients and a 90-day good neurological outcome rate of 29% versus 51%, respectively.3 The low rate of favorable outcomes associated with patient transfer raises questions about the effectiveness of the current inter-facility transfer paradigm. A more encompassing variable metric that would encapsulate the entire spectrum of the patient's care would be the time from first medical contact to reperfusion. This would be a more comprehensive and comparable metric that would integrate the pre-hospital and inter-facility transfer timelines. The current model in the USA of taking a patient to a primary stroke center for delivery of intravenous tissue plasminogen activator prior to transportation to an endovascular-ready center may be challenged in the face of recent clinical data showing a strong efficacy of endovascular reperfusion treatments. It will be important to develop a pre-hospital triage scale to enable emergency medical service providers to distinguish between patients with a possible large stroke syndrome where direct transportation to an endovascular-ready center is best for the patient. This trial was performed in patients with ST segment elevation myocardial infarction (STEMI) in the PRAGUE-220 and DANAMI-221 trials where it was shown that percutaneous coronary intervention (PCI) for STEMI was more effective than stopping for thrombolysis prior to PCI. Although an ECG for the brain does not exist in the field, clinical tools such as the Los Angeles Motor Scale22 may be sensitive enough to triage patients without having to incur time delays by stopping at a primary stroke center first.

There are several limitations to the current analysis. The MERCI registry is a site adjudicated registry for outcomes and thus there may be biases inherent to the retrospective nature of the registry. Second, several time points were not available for analysis, thus limiting our ability to report on specific bottlenecks that may be causing the delays. Third, the types of imaging employed and pre-treatment core infarcts prior to treatment are not accounted for in regression analysis. Last, there is variability in practice patterns that may exist leading to the variances noted in this analysis.23 The SDs are quite large, probably because of the heterogeneity that exists among treatment sites. Standardization of time metrics and targets similar to that achieved with the Target Stroke Initiative may allow for a reporting standard for the treating center.

Despite the limitations, the study confirms the importance of times to treatment and their impact on neurological recovery after endovascular stroke therapy. The time from last known normal to reperfusion has not changed over the decade studied despite an improvement in the procedure times and door to puncture times. There are several opportunities to work towards a standard time metric that encapsulates first medical contact to reperfusion as a meaningful standard across studies.