Longer door-in-door-out (DIDO) times during interhospital transfer for endovascular therapy (EVT) are associated with significantly lower rates of EVT, higher complication rates, and worse functional outcomes in patients with acute ischemic stroke, a large US cohort study showed.

Using nationwide data from the Get With The Guidelines-Stroke (GWTG-Stroke) registry, investigators found a strong association between longer DIDO times at referring hospitals and increased disability at hospital discharge, even after adjusting for patient demographics and risk factors, receiving hospital, and clinical characteristics.

“This study provides new and compelling evidence that greater attention should be paid to developing efficiencies within regional stroke systems of care and hub-and-spoke networks with a targeted focus on minimizing DIDO times at transferring hospitals,” lead investigator Regina Royan, MD, MPH, Department of Emergency Medicine and Department of Neurology, University of Michigan, Ann Arbor, Michigan, and colleagues wrote.

The study was published online on January 21 in The Lancet Neurology.

Transfer Time Matters

EVT is a highly time-sensitive and effective treatment that can reduce disability from acute ischemic stroke, yet nearly half of patients in the US who receive EVT require interhospital transfer.

The American Heart Association/American Stroke Association recommends a DIDO time of no more than 90 minutes, but real-world data show the median DIDO often exceeds the standard at 132 minutes, the investigators noted.

To assess the effect of transfer time delays, investigators conducted a retrospective cohort study of 22,140 adult patients (median age, 70 years; female, 50.1%; White, 73.9%) with acute ischemic stroke and confirmed vessel occlusion on cerebrovascular imaging. These patients were transferred to EVT-capable hospitals between 2019 and 2023.

Median DIDO time was 121 minutes, with only 26% of patients who met the recommended goal of 90 minutes or less. Overall, 75.8% of patients received EVT.

Investigators also assessed whether this translated directly to poorer clinical outcomes for patients who experienced the longest transfer delays for EVT.

“We have made tremendous progress in getting people timely acute stroke treatment after they arrive at the emergency department…but the next frontier of acute stroke systems of care is improving interhospital transfer times,” senior author Shyam Prabhakaran, MD, MS, chair of neurology at the University of Chicago, Chicago, noted in a press release. He added that every passing minute increases the risk of losing neurologic functioning.

Worse Disability, Less EVT, More Complications

The primary outcome of the study was functional status at hospital discharge, measured by the modified Rankin Scale (mRS), an ordinal 0-6 scale in which 0 indicates no symptoms, 1-2 mild disability, 3-5 increasing levels of disability, and 6 death.

Compared with patients transferred within 90 minutes, those with longer DIDO times had progressively worse outcomes. For a 1-point worsening in mRS score, adjusted odds ratios (aORs) were 1.29 (95% CI, 1.20-1.37) for 91-180 minutes, 1.49 (95% CI, 1.36-1.64) for 181-270 minutes, and 1.70 (95% CI, 1.53-1.89) for delays exceeding 270 minutes.

Longer delays were also associated with higher odds of moderate-to-severe disability (mRS, 3-6). Specifically, patients with DIDO times over 270 minutes had an aOR of 1.63 (95% CI, 1.39-1.90) for disability and an aOR of 1.60 (95% CI, 1.39-1.84) for severe disability or death.

Transfer delays also reduced the likelihood that patients ultimately received EVT, with those delayed over 270 minutes having 65% lower odds of undergoing the procedure.

Longer DIDO times were also associated with worse mobility and higher complication rates. Compared with the < 90-minute group, those with the longest delays (> 270 minutes) had lower odds of independent ambulation (aOR, 0.67; 95% CI, 0.58-0.77) and lower odds of having no complications after EVT or intravenous thrombolysis (aOR, 0.74; 95% CI, 0.61-0.88).

This suggests “the ability or willingness to perform endovascular therapy might wane when patients arrive later in the therapeutic window,” the investigators wrote.

The investigators acknowledged several study limitations, including that functional outcomes were assessed at hospital discharge rather than the standard 90-day mark. The registry also lacked interhospital transport times and detailed neuroimaging variables known to influence outcomes after EVT.

Finally, due to its observational nature, the findings cannot establish causality, although a randomized trial testing whether reducing DIDO times improves outcomes is currently underway.

Is a 60-Minute Goal Achievable?

In an accompanying editorial, Bernard P. L. Chan, MD, Department of Medicine, Division of Neurology, National University Hospital, National University Health System, Singapore, wrote that the study “firmly establishes the importance of DIDO times” for transfer patients with stroke.

Chan, who was not involved in the current study, noted that the benefit of faster hospital transfers did not appear to have a specific cutoff point, but rather, faster times were associated with better recovery. Based on this, he suggested that the 90-minute target may not be aggressive enough.

He added that “analyses using dichotomous cutoffs showed benefits with both DIDO times of less than 90 min and of less than 60 min.”

“It is therefore reasonable to further decrease the target DIDO time to 60 min in centers that have already achieved the 90-min target and those that have door-to-needle times of within 30 min,” Chan noted. He pointed out that there are some international stroke teams that are accustomed to faster clinical goals.

He concluded that in many countries, stroke nurses have already started to use digital clocks to monitor door-to-needle and door-to-puncture times. “Do not be surprised if they soon also start monitoring DIDO times,” Chan added.

The GWTG-Stroke program is provided by the American Heart Association and is sponsored, in part, by Novartis, Novo Nordisk, AstraZeneca, Bayer, and HCA Healthcare. Royan reported receiving funding from the National Institute of Neurological Disorders and Stroke. Prabhakaran reported receiving funding from the National Institutes of Health Agency for Healthcare Research and Quality and the National Institute of Neurological Disorders and Stroke. Chan reported having received research support and travel funding from the National University Health System, Singapore.