INTERHOSPITAL TRANSFER OR DIRECT TRANSPORT TO SPECIALIZED CENTRES FOR THROMBECTOMY: INTERPRETATION OF QUÉBEC RESULTS IN LIGHT OF LATE BREAKING REAL-WORLD EVIDENCE

2019 CADTH Symposium

Michèle de Guise, MD, FRCPc Director of health technology assessment, INESSS on behalf of the Cardio-neurovascular Evaluation Unit

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INESSS is publicly funded.

I have no actual or potential conflict of interest in relation to this topic or presentation.

DISCLOSURE

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To reflect on how RWData and RWE are complementary to RCTs in order to provide more adapted and contextualized recommendations.

Using as case study the mandate we received from the Ministry of health to evaluate how to optimize access to endovascular treatment (EVT, i.e. thrombectomy) in Québec, focusing on the optimal pathway.

PURPOSE OF THIS PRESENTATION

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STRUCTURE OF THE SYSTEM OF STROKE CARE IN QUÉBEC (2017-18)

80 hospitals providing different levels of care, 4 thrombectomy programs concentrated in urban areas

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First medical contact

Non tertiary (NT) centre

EVT centre Triage EVT (Door) Scan Needle

t-PA

First arterial puncture

Departure from NT centre

Triage NT (Door) Scan Needle

t-PA

Symptoms

PATIENT FAMILY

PREHOSPITAL (EMS)

REFERRAL (NT) CENTRES

INTERHOSPITAL (EMS)

EVT CENTRES

PATIENT TRAJECTORY FOR EVT TREATMENT

POST-PROCEDURE CARE AND REHABILITATION

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SYNTHESIS OF ALL TYPES OF EVIDENCE

TO DEVELOP PROPOSED RECOMMENDATIONS

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• Meta-analyses of five randomized trials: • In comparison to thrombolysis, thrombectomy is associated with

improved patient outcomes if treatment is received within 7 hours of the start of symptoms

• The shorter the treatment delays, the better the outcomes.

• Among 1000 patients achieving endovascular reperfusion;

• For every 15 minutes faster emergency department door-to- reperfusion time • 39 patients would have less-disabled outcome at 3 months • 25 among those would achieve functionnal independence

• Assuming we can replicate the condition of the RCTs

SCIENTIFIC EVIDENCE

HERMES collaboration: Saver et al. and Goyal et al. (2016)

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• Selection criteria for patients:

the vast majority were functionally independent pre-stroke mRankin score ≤2

2/5 trials had age restrictions (e.g., ≤80 years old)

• Selection criteria for participating centres: high volume

e.g. ≥40-60 EVT/year; >500 stroke patients/year

high expertise

• Study protocols emphasized fast treatment

Thus, patients and hospitals not necessarily representative of those in the real-world context of stroke care

RCT SELECTION CRITERIA

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Observation period April 1, 2017 March 31, 2018

Hospitals All hospitals with an EVT program (n=4)

Patients All patients who presented to an emergency room (by ambulance or other means) and were treated with t-PA or EVT in an EVT centre

Data collection

Documentation by EVT clinical teams

Data collection by INESSS

Centralized secure web site (REDCap)

Data validation Read only access to REDCap

Validation of preliminary results by EVT teams

Data analysis Analysis by INESSS in collaboration with clinical expert committee (reps from each EVT program)

FIELD EVALUATION OF EVT BY INESSS

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VOLUME EVT ± t-PA (2017-18)

183

80 77

35

0

20

40

60

80

100

120

140

160

180

200

A B C D

Total volume EVT ± t-PA in Québec = 375

The four thrombectomy centers have a wide range in volume of cases

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PATIENT CHARACTERISTICS: RCT VS QUÉBEC (1)

RCT meta-analysis

N=634

Québec 2017-18 N=375

Median age in years (25th-75th percentile)

68 (57-77)

71 (60-80)

Age ≥ 80 years 17% 29%

Women 48% 51%

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PATIENT CHARACTERISTICS: RCT VS QUÉBEC (2)

RCT meta-analysis

N=634

Québec 2017-18 N=375

Pre-stroke mRankin ≤ 2 98% 94%

Median (25th-75th percentile)

Initial ASPECTS score 9

(7-10) 9

(7-10)

Initial NIHSS score 17

(14-20) 16

(11-20)

Start of symptoms to triage at EVT centre (door)

99 min (52-191)

151 min (60-222)

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•American registry publication (online Jan 31, 2019): 37,260 EVT patients treated at 639 centres, 2012-17

LATE-BREAKING EVIDENCE

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RCTs N=634

Québec N=375

USA N=37,260

Mode of arrival: Direct admission Interhospital transfer

70% 30%

41% 59%

57% 42%

Use of t-PA 83% 61% 58%

PROCESSES: RCT VS QUÉBEC VS USA REGISTRY

The proportion of transferred patients in Québec were much more similar to the US registry than to the RCTs, but still higher. The proportion of use of t-PA was much more similar to the US registry

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RCT VS QUÉBEC VS USA REGISTRY TREATMENT DELAYS FOR TRANSFERRED PATIENTS

RCT N=184

Québec N=209

USA N=15,975

Median delay: Start of symptoms to EVT (25th-75th percentile)

295 (255-342)

247 (202-310)

289 (NR)

Median delay: Door of EVT centre to EVT (25th-75th percentile)

81 (58-105)

25 (14-43)

68 (NR)

For transferred patients, delays from symptoms to hospital arrival and from triage to thrombectomy results were favourable in comparison to both the trials and the American registry

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RCT VS QUÉBEC VS USA REGISTRY TREATMENT DELAYS FOR DIRECTLY ADMITTED PATIENTS

RCT N=421

Québec N=166

USA N=21,285

Median delay: Start of symptoms to EVT (25th-75th percentile)

210 (158-270)

135 (107-185)

213 (NR)

Median delay: Door of EVT centre to EVT (25th-75th percentile)

116 (82-160

70 (50-100)

128 (NR)

Shorter delays from triage to thrombectomy showed the good performance of our current thrombectomy programs

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Outcome Transferred

patients N=15,975

Directly admitted patients

N=21,285

OR (95% CI)

Adjusted OR for treatment

delay (95% CI)

In-hospital mortality 14.7% 13.4%

1.17 (1.10, 1.24)

1.01 (0.92, 1.11)

P=ns

Independent ambulation at discharge

33.1% 37.2% 0.80

(0.76, 0.85)

0.87 (0.80, 0.95)

P=0.002

USA REGISTRY EVIDENCE ON OUTCOMES

Shah et al., 2019

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USA REGISTRY EVIDENCE ON OUTCOMES

Shah et al., 2019

In comparison to patients treated after inter-hospital transfer,

Direct admission EVT was associated with :

• Significant decrease in in-hospital mortality

• Significant increase in independent ambulation at hospital discharge

• The decrease in mortality was no longer significant after adjustment for differences in treatment delays • Time is brain !

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New evidence from our own context in Québec and from a large registry :

•Was comforting in terms of implementation of the EVT programs in Québec;

•Added weight to the conclusions of the RCT meta-analyses that “Time is brain”;

• Increased the strength of our recommendations concerning prioritization of direct transport for EVT;

•Showed the importance of documentation of real-world outcomes to aid decision-making.

CONCLUSION

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