What defines success following reperfusion after mechanical thrombectomy for older patients in the real world?

Introduction

Patients 85 years or older are under-represented in randomized clinical trials of endovascular mechanical thrombectomy (MT) due to large vessel occlusion of the anterior circulation.¹ Given a possible selection bias and exclusion of this vulnerable demographic, caution is needed when extrapolating from existing data.^1,2 Several small, retrospective studies suggest that older patients have higher rates of in-hospital complications, mortality rates, and poorer functional outcomes following successful MT compared to younger patients.^3-5 While MT is generally recommended in this population, little is known about how best to engage with patients and their families in the shared decision-making process around MT and weighing possible long-term outcomes with patients’ preferences around the use of invasive interventions towards the end of life.⁶ We therefore chose a mixed methods approach to (1) evaluate quantitatively 90-day clinical outcomes among patients ≥ 85 years who underwent successful MT and (2) explore qualitatively the decision-making process around MT and subsequent decisions to withhold or withdraw life-sustaining treatment (WLST).

Methods

Data were collected from a comprehensive stroke center in the northwestern United States, between June 2016 and December 2019. We included all patients age ≥ 85 years who presented as acute stroke codes with anterior circulation large vessel occlusion and underwent successful reperfusion. We defined successful reperfusion by Thrombolysis in Cerebral Infarction (TICI) scale as partial filling ≥ 50% territory to complete reperfusion (TICI 2b-3).

We reviewed medical records to collect demographic, clinical, and radiological data. Primary outcome was modified Rankin Scale Score (mRS) at 90 days after presentation, a measure of disability, commonly used for outcome after ischemic stroke.¹ A good outcome was defined as mRS 0-2 or recovery back to baseline for those presenting with mRS >2. Quantitative analysis was descriptive.

For qualitative analysis of the decision-making process around MT and WT.ST, one member of the investigative team (AR) searched the electronic medical record and selected all documentation pertaining to (1) MT consent and patient code status, (2) progress, attending, and family meeting notes, and (3) palliative care consultation notes. Given the small cohort, we included all patients who met inclusion criteria (convenience sampling). Subsequently, two investigators (AR and CJC), initially blinded to patient outcome, reviewed the notes and utilized a constant comparative method as a framework to identify emerging concepts.⁷ In an iterative process, we used thematic analysis to arrive at key themes.

The study protocol was approved by the Institutional Review Board of the University of Washington.

Results

Over the 3.5-year period, 44 patients ≥ 85 years presented to our hospital with an acute ischemic stroke and an anterior circulation large vessel occlusion based on CT angiography. Of these individuals, 36 (82%) achieved good reperfusion (TICI scale 2b-3), 6 (14%) achieved TICI 0-2a, and 2 (4%) had spontaneous recanalization (Figure 1). Mean age of the 36 patients with good reperfusion was 88.8 years; 22 (61%) were women. Fifteen patients (42%) had a pre-stroke mRS >2 (Figure 2); 11 lived in an assisted living or skilled nursing facility (SNF), and 4 at home with caregivers. Pre-stroke advance care planning was documented in 23 (64%), most of whom wanted limited intervention including no chest compressions, intubation, artificial nutrition, or some combination of these. Additional characteristics can be found in Table 1.

Figure 1: Cohort Identification/Selection.

We used our stroke registry to search for patients ages 85 years or older who presented to our hospital as a ‘stroke code’ with an acute ischemic stroke. We selected all those who were found to have a large vessel occlusion (LVO) of the anterior circulation on CT angiography and achieved successful reperfusion after mechanical thrombectomy (MT).

Figure 2: Pre-stroke and 90-day mRS following successful thrombectomy with good reperfusion.

Pre-stroke and 90-day mRS in 36 patients ≥ 85 years of age who underwent successful thrombectomy defined as partial filling ≥ 50% territory to complete reperfusion (TICI 2b-3). Two patients maintained their pre-stroke mRS following MT: 1 with mRS 0-2 and 1 with mRS 3.

Table 1.

Patient characteristics.

Characteristics	TICI 2b-3 n=36
Age, mean years (SD)	88.8 (3.5)
Women	22 (61%)
Direct admission	23 (64%)
Pre-stroke advance care planning	23 (64%)
- Limited intervention*	21 (58%)
Pre-stroke mRS 0-2	21 (58%)
Full Code on Admit	16 (44%)
Initial NIH Stroke Scale (mean, SD)	20 (6)
Received IV tPA	19 (53%)
ASPECTS, mean (SD)	8 (1.6)
Door to MT, median minutes (IQR)	67.5 (51-95)
Hospital LOS, median days (IQR)	6.5 (3-10)
Palliative Care Consult	8 (22%)
WLST during hospitalization	19 (53)
Death at 90-days post-stroke	26 (72%)

ASPECTS = Alberta Stroke Program Early CT score; IQR, interquartile range; and LOS, length of stay.

^*Limited intervention included no chest compressions, intubation, artificial nutrition, or some combination of these.

Among the 19 patients for whom the focus of care was changed in-hospital towards WLST (53%), median time to WLST was 3 days (range 1 to 37 days) with 6 (32%) transitioning within 24 hours. Intracranial complications were more common in patients who had WLST compared to those who did not, see Table 2.

Table 2.

In-hospital complications in patients who did vs. did not undergo withholding or withdrawal of life-sustaining treatment

		WLST
In-Hospital Complications	All n=36	Yes (n=19)	No (n=17)
Infection	12 (33%)	4 (21%)	8 (47%)
Intracranial complications *	12 (33%)	11 (30%)	1 (6%)
Bleeding	8 (22%)	7 (37%)	1 (6%)
Cerebral edema and herniation	4 (4%)	4 (21%)	0 (0%)
Other extracranial complications	7 (19%)	2 (11%)	5 (29%)
Delirium	2 (6%)	1 (5%)	1 (6%)
Cardiac complications	3 (8%	0 (0%)	3 (18%)
Other bleeding	2 (6%)	1 (5%)	1 (6%)
Any of these complications	26 (72%)	15 (79%)	11 (65%)

^*Only intracranial complication (P=0.02 by Fisher exact test) and intracranial bleeding (P=0.04 by Fisher exact test) were significantly more common in those who had withholding or withdrawal of life-sustaining treatment (WLST) compared to those who did not. A trend was present for cerebral edema and herniation.

Overall, two-thirds of patients were discharged from the hospital alive (n=24), of whom 7 were discharged to hospice and 10 were discharged to a SNF without hospice. By 90 days, twenty-six patients (72%) had died including all those who had discharged to hospice, 8 (22%) survived with poor outcome, and two had a good outcome (6%), including one with mRS 0 and one who recovered back to their previous mRS 3 (Figure 2). Of the 10 patients who discharged to SNF, 90-day outcome was death in 5, mRS 5 in 4 and mRS 3 in 1.

Treatment decisions

We reviewed over 100 EMR documents qualitatively. Early conversation around MT was not explicitly documented except for basic consent, and the decision leading to MT was usually considered in retrospect. Exploring the decision-making processes, we identified 2 key themes that centered around (1) a rapid, default decision for MT and (2) a slower, deliberative process about WLST.

(1) The decision for MT was guided by the possibility of any improvement and a hope for full reversal of deficits.

Patient 21494 (Resident progress note): “Patient's daughter… stated that [patient] would want to try aggressive interventions initially.”

Even families of patients who were dependent prior to admission may have hoped for full reversal of deficits.

Patient 22617 (attending note): “They were very clear that [patient] was already not happy […] prior to this hospitalization and that any disability would not be acceptable.”

(2) Later in the course, the choice to transition the focus of care towards WLST was a consequence of shared deliberation of patient’s prognosis, values, and realistic treatment goals. Families shared a low tolerance for decreased quality of life for their loved one. If their hopes for recovery were not realized within days, or the patient experienced a medical complication, a decision was made quickly to transition the patient to comfort measures only.

Patient 23526 (palliative care note): “Her family notes that she has always defined her quality of life by both mental and functional independence, and they worry that even with further recovery, [patient] will remain dependent for cares and that this would not fit with her prior stated definition of quality of life.”

For additional direct quotes from the medical records, see table 3.

Table 3.

De-identified direct quotes from the medical record illustrating two key themes identified through qualitative analysis

Patient	Theme A: Mechanical thrombectomy itself was considered a rapid, default decision	Theme B: The decision to withhold or withdraw life-sustaining treatment later in the course occurred after deliberation of prognosis, values, and realistic treatment goals
21494	Progress note post-MT day 1: “Patient's daughter… stated that [patient] would want to try aggressive interventions initially”	Progress note post-MT day1: “[daughter] states if [patient] would be left with lasting deficits such as paralysis [patient] would not want to live that way.”
22617	Social Work note on day of admission: “The pt's family was clear that they wanted as much done for the pt as possible.”	Attending note within 24hrs of admission: “They were very clear that [patient] was already not happy with [quality of life] prior to this hospitalization and that any disability would not be acceptable. They asked that we spare [patient] more tests and focus on not suffering.”
23645	Resident admission note: “He is currently DNR/DNI with advanced dementia but they thought that if there was a reasonable chance that he may improve with this therapy it was worth the risks…”.	Palliative care note: “They are both clear that [patient] would not want to be maintained in [patient’s] current situation, with very little likelihood of recovering to previous state of dementia (in which [patient] did enjoy eating, being with family, listening to music).”
22312	Interventionalist note post-MT: “After a thorough discussion of the risks and benefits, the patient's family gave informed consent and asked us to proceed.”	Family meeting note within 24 hours of admission: “[daughter] notes that [patient] has refused many medical therapies in the past and states that "he has made peace a long time ago and says that when it is his time to go, he is ready." Discharge summary: “family expressed that patient always enjoyed talking, was uncertain if [patient] would want to continue with aggressive care if [patient] were to be aphasic.”
23183	Ambulance record: “POLST order comfort measures only (per family DPOA wants stroke protocol used).” Progress note >24 hours of admission: “the sons did not want her to suffer for long but at the same time wanted to give her time to see if she improves.”	Attending note hospital day 3: “Met with sons today and discussed goals of care. Patient reportedly did not want to be in a SNF. Sons agreed that current treatment appear to not be in line with [patient’s] prior stated goals. Decision made to transition to comfort care orders alone.”
22004	Admit/code status note “Discussed with wife the rationale, risks and alternatives to tPA and thrombectomy, and she was agreeable to both… pt is DNR but temporary intubation OK”	Code status note: “We discussed pt's wishes, as expressed earlier in [patient’s] life, that [patient] would not want life prolonged in the event that [patient] could not once again become independent.”
23526	MT pursued after family/DPOA consent, no further documentation on MT consent process beyond procedural risks and benefits.	Palliative care note: “Her family notes that she has always defined her quality of life by both mental and functional independence, and they worry that even with further recovery, [patient] will remain dependent for cares and that this would not fit with her prior stated definition of quality of life.”
23830	MT pursued after family/DPOA consent, no further documentation on MT consent process beyond procedural risks and benefits.	Family meeting note:“Specifically, [patient] valued her social life and ability to communicate and engage freely with others, live independently, the ability to read, and to not be burdened by extensive medical treatments and rehabilitation-she would not want to continue with any form of treatment that would not lead to a prognosis that would not allow her to live with those goals.”
22346	Progress note >24 hours: “ASPECT score 10 on arrival and patient was subsequently taken for thrombectomy with consent obtained by daughter/DPOA.” Social work note within 24 hours of MT: “Daughter reports concern aboutwhether she "made the right decision to have all this done," referring to consent for intervention”	No detailed GOC conversation documented, “patient did not want artificial nutrition. Patient remains DNR/DNI.”

Discussion

Our single-center retrospective cohort study suggests overall poor outcomes after MT in older patients, often combined with in-hospital complications and pre-stroke functional dependence, consistent with prior studies.^3-6 Whereas the rate of WLST is not reported in these studies, the literature suggests that most early deaths after stroke occur after WLST, particularly in men, older patients, and those with a poor clinical prognosis.^8,9 Within our cohort, this transition of the focus of medical care appears to be based on patients’ previously expressed goals to avoid suffering, their immediate post-MT functional status, and development of intracranial complications. Ambiguity rules when considering what defines a poor prognosis from the family perspective as they must weigh not only medical implications but what their loved one considered an acceptable quality of life. At least 19 of our 25 decedents died after a decision to pursue WLST. Our qualitative findings suggest a low tolerance for any degree of additional dependence or suffering, even short-term, which may, in part, explain the relatively short time from MT to WLST in this elderly population.

This study has several limitations, including small sample size, single-center design, and a lack of information about patients who declined thrombectomy. In addition, timing or content of family meetings or indications for palliative care consultation were not standardized. Biases in physician prognostication that influenced decision-making are possible and were not controlled for. without knowing the ‘right’ or ‘best’ approach to MT in older patients, it is possible that MT was not concordant with some of our patient’s treatment goals. Finally, the decision-making observed in this study, in particular around WLST may not be generalizable to other cultural settings.

Despite these limitations, this study raises important questions regarding how a patient’s pre-stroke functional baseline and quality of life may drive decision-making in pursuing MT, WLST, or both. As the clinical and financial ramifications of considering MT are substantial, a standardized approach to the informed consent process leading to MT should be considered that provides realistic expectations of possible outcomes and balances these with a patient’s acceptable burden of treatment. Future studies could include evaluation of a communication intervention to improve such emergent goals of care conversations, or an advance care planning process for patients at high risk of stroke that would include the possibility of MT in advance.