Time to Reperfusion and Treatment Effect for Acute Ischemic Stroke: A Randomized Clinical Trial.
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BORIS DOI
Publisher DOI
PubMed ID
26716735
Description
IMPORTANCE
Intra-arterial treatment (IAT) for acute ischemic stroke caused by intracranial arterial occlusion leads to improved functional outcome in patients treated within 6 hours after onset. The influence of treatment delay on treatment effect is not yet known.
OBJECTIVE
To evaluate the influence of time from stroke onset to the start of treatment and from stroke onset to reperfusion on the effect of IAT.
DESIGN, SETTING, AND PARTICIPANTS
The Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands (MR CLEAN) was a multicenter, randomized clinical open-label trial of IAT vs no IAT in 500 patients. The time to the start of treatment was defined as the time from onset of symptoms to groin puncture (TOG). The time from onset of treatment to reperfusion (TOR) was defined as the time to reopening the vessel occlusion or the end of the procedure in cases for which reperfusion was not achieved. Data were collected from December 3, 2010, to June 3, 2014, and analyzed (intention to treat) from July 1, 2014, to September 19, 2015.
MAIN OUTCOMES AND MEASURES
Main outcome was the modified Rankin Scale (mRS) score for functional outcome (range, 0 [no symptoms] to 6 [death]). Multiple ordinal logistic regression analysis estimated the effect of treatment and tested for the interaction of time to randomization, TOG, and TOR with treatment. The effect of treatment as a risk difference on reaching independence (mRS score, 0-2) was computed as a function of TOG and TOR. Calculations were adjusted for age, National Institutes of Health Stroke Scale score, previous stroke, atrial fibrillation, diabetes mellitus, and intracranial arterial terminus occlusion.
RESULTS
Among 500 patients (58% male; median age, 67 years), the median TOG was 260 (interquartile range [IQR], 210-311) minutes; median TOR, 340 (IQR, 274-395) minutes. An interaction between TOR and treatment (P = .04) existed, but not between TOG and treatment (P = .26). The adjusted risk difference (95% CI) was 25.9% (8.3%-44.4%) when reperfusion was reached at 3 hours, 18.8% (6.6%-32.6%) at 4 hours, and 6.7% (0.4%-14.5%) at 6 hours.
CONCLUSION AND RELEVANCE
For every hour of reperfusion delay, the initially large benefit of IAT decreases; the absolute risk difference for a good outcome is reduced by 6% per hour of delay. Patients with acute ischemic stroke require immediate diagnostic workup and IAT in case of intracranial arterial vessel occlusion.
TRIAL REGISTRATION
trialregister.nl Identifier: NTR1804.
Intra-arterial treatment (IAT) for acute ischemic stroke caused by intracranial arterial occlusion leads to improved functional outcome in patients treated within 6 hours after onset. The influence of treatment delay on treatment effect is not yet known.
OBJECTIVE
To evaluate the influence of time from stroke onset to the start of treatment and from stroke onset to reperfusion on the effect of IAT.
DESIGN, SETTING, AND PARTICIPANTS
The Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands (MR CLEAN) was a multicenter, randomized clinical open-label trial of IAT vs no IAT in 500 patients. The time to the start of treatment was defined as the time from onset of symptoms to groin puncture (TOG). The time from onset of treatment to reperfusion (TOR) was defined as the time to reopening the vessel occlusion or the end of the procedure in cases for which reperfusion was not achieved. Data were collected from December 3, 2010, to June 3, 2014, and analyzed (intention to treat) from July 1, 2014, to September 19, 2015.
MAIN OUTCOMES AND MEASURES
Main outcome was the modified Rankin Scale (mRS) score for functional outcome (range, 0 [no symptoms] to 6 [death]). Multiple ordinal logistic regression analysis estimated the effect of treatment and tested for the interaction of time to randomization, TOG, and TOR with treatment. The effect of treatment as a risk difference on reaching independence (mRS score, 0-2) was computed as a function of TOG and TOR. Calculations were adjusted for age, National Institutes of Health Stroke Scale score, previous stroke, atrial fibrillation, diabetes mellitus, and intracranial arterial terminus occlusion.
RESULTS
Among 500 patients (58% male; median age, 67 years), the median TOG was 260 (interquartile range [IQR], 210-311) minutes; median TOR, 340 (IQR, 274-395) minutes. An interaction between TOR and treatment (P = .04) existed, but not between TOG and treatment (P = .26). The adjusted risk difference (95% CI) was 25.9% (8.3%-44.4%) when reperfusion was reached at 3 hours, 18.8% (6.6%-32.6%) at 4 hours, and 6.7% (0.4%-14.5%) at 6 hours.
CONCLUSION AND RELEVANCE
For every hour of reperfusion delay, the initially large benefit of IAT decreases; the absolute risk difference for a good outcome is reduced by 6% per hour of delay. Patients with acute ischemic stroke require immediate diagnostic workup and IAT in case of intracranial arterial vessel occlusion.
TRIAL REGISTRATION
trialregister.nl Identifier: NTR1804.
Date of Publication
2016-02
Publication Type
Article
Subject(s)
Language(s)
en
Contributor(s)
Fransen, Puck S S | |
Berkhemer, Olvert A | |
Lingsma, Hester F | |
Beumer, Debbie | |
van den Berg, Lucie A | |
Yoo, Albert J | |
Schonewille, Wouter J | |
Vos, Jan Albert | |
Nederkoorn, Paul J | |
Wermer, Marieke J H | |
van Walderveen, Marianne A A | |
Staals, Julie | |
Hofmeijer, Jeannette | |
van Oostayen, Jacques A | |
Lycklama À Nijeholt, Geert J | |
Boiten, Jelis | |
Brouwer, Patrick A | |
Emmer, Bart J | |
de Bruijn, Sebastiaan F | |
van Dijk, Lukas C | |
Kappelle, L Jaap | |
Lo, Rob H | |
van Dijk, Ewoud J | |
de Vries, Joost | |
de Kort, Paul L M | |
van den Berg, J S Peter | |
van Hasselt, Boudewijn A A M | |
Aerden, Leo A M | |
Dallinga, René J | |
Visser, Marieke C | |
Bot, Joseph C J | |
Vroomen, Patrick C | |
Eshghi, Omid | |
Schreuder, Tobien H C M L | |
Heijboer, Roel J J | |
Keizer, Koos | |
Tielbeek, Alexander V | |
den Hertog, Heleen M | |
Gerrits, Dick G | |
van den Berg-Vos, Renske M | |
Karas, Giorgos B | |
Steyerberg, Ewout W | |
Flach, H Zwenneke | |
Marquering, Henk A | |
Sprengers, Marieke E S | |
Jenniskens, Sjoerd F M | |
Beenen, Ludo F M | |
van den Berg, René | |
Koudstaal, Peter J | |
van Zwam, Wim H | |
Roos, Yvo B W E M | |
van Oostenbrugge, Robert J | |
Majoie, Charles B L M | |
van der Lugt, Aad | |
Dippel, Diederik W J |
Additional Credits
Series
JAMA neurology
Publisher
American Medical Association
ISSN
2168-6157
Access(Rights)
restricted