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Stroke Care in Patients with CKDConsiderations in Acute Care

Michael J. Lyerly, MDUniversity of Alabama at Birmingham

Birmingham VAMC

Disclosures

• No Financial Disclosures relevant to thisProgram

• Salary support through NIH StrokeNet includingARCADIA/ARCADIA CSI

• I will be discussing off-label use of IV alteplasefor the treatment of acute ischemic stroke

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Outline

• The General Approach to an Acute Stroke Patient

• Acute Care for CKD Patients

• Thrombolytics

• Intra-arterial Therapies

• General Medical Management

The General Approach to an Acute Stroke Patient

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Why Does Stroke Matter?

• 800,000 new strokes each year

• 200,000 recurrent strokes each year

• 5th leading cause of death in the US

• An American has a stroke every 40 seconds and someone dies from a stroke every 4 minutes

• Up to 30% of survivors have significant long term disability

Virani et al. Circulation. 2020. 

The Stroke Chain of Survival

– Detection: Patient or bystander recognition

– Dispatch: Activation of 9-1-1 and priority EMS dispatch

– Delivery: Prompt triage and transport to the most appropriate stroke hospital and prehospital notification

– Door: Immediate ED triage to a high acuity area

– Data: Prompt ED evaluation, stroke team activation, laboratory studies and brain imaging

– Decision: Diagnosis and determination of most appropriate therapy; Discussion with patient and family

– Drug: Administration of appropriate drugs or other interventions

– Disposition: Timely admission to a stroke unit

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Key Components of Emergency Stroke Care

• Ensure Medical Stability • Keep the patient NPO• Focused History and Examination

– Last Known Well Time

– Symptoms and Progression

– Medical History and Medications

• Laboratory Studies– CBC, CMP, Coagulation Studies, Glucose

• Imaging

CT Head CT Angiography CT Perfusion

Acute Stroke Therapies

• Intra-arterial Revascularization

• Thrombolytics

• Supportive Medical CareDO NOT

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Acute Care for CKD Patients

CKD in Patients Presenting with Acute Stroke

• Despite improvements in care and survival of patients with cardiovascular disease, patients with CKD, particularly those on dialysis, seem to have worse cardiovascular outcomes.

• In general, the neurologic manifestations of stroke in CKD patients do not differ from the general population.

• Given that CKD patients may harbor more advanced vascular disease, these patients may have more advanced baseline cerebrovascular disease burden and reduced cognitive reserve– Pre-existing physical and neurologic disability

– Pre-existing cognitive deficits

– Hemodynamic effects from dialysis

• Up to 1 in 3 AIS patients have some form of renal dysfunction ( <60 ml/min)

Roberts et al. Am J Kidney Disease. 2011.Weiner et al. Sem Nephrology. 2015.  Tamura et a. Neurology. 2012.Rowat et al. Int J Stroke. 2014. DO N

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Muntner et al. Neph Dial Trans. 2011.

Delays in Presentation and Diagnosis

• The CHOICE study (cohort of 165 ESRD patients) suggested prolonged initial symptom recognition and presentation– Median time from symptom onset to ED presentation

was > 8 hours

• Factors underlying this have not been described– Knowledge of stroke signs/symptoms?

– Influence of premorbid physical and cognitive deficits?

– Socioeconomic factors?

• Opportunity for educationSozio et al. Am J Kidney Disease. 2009.DO N

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Imaging Studies

• Protocols for CTA/CTP differ by institution– CTA: 70-130 ml

– CTP 40-80 ml

• Many institutions have struggled to determine how to implement CTA/CTP for widespread use in acute stroke patients

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• Many academic centers perform CTA/P without creatinine but this is not standard or generalizable to community hospitals

• Is this appropriate for all patients?– Endovascular ineligible patients?

– Low likelihood for Large Vessel Occlusion?

– Known CKD? Powers et al. Stroke. 2019.

Thrombolysis with Alteplase

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Alteplase

• Recombinant tissue plasminogen activator

• Serine Protease

• Additionally used for MI, PTE, clot thrombolysis

Cathflo.com

• Randomized, double-blind trial of IV alteplase vs. placebo given within 3 hours of symptoms onset

• At 90 days, patients treated with alteplase were more likely to have minimal or no disability (38 vs 21%)

– This benefit was sustained one year later.

• Symptomatic intracerebral hemorrhage (sICH) within 36 hours after onset occurred in 6.4% of patients treated with alteplase (0.6% in placebo)

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• Treatment with alteplase 3-4.5 hours from symptom onset (821 pts)

• More favorable outcomes (modified Rankin Scale) at 90 days in the alteplase group (52% vs 45%, OR 1.34)

• Higher rates of symptomatic hemorrhage in the alteplasegroup (2.4% vs 0.2%); however, mortality did not differ– Hemorrhage rate was 7.9% using the NINDS definition

Alteplase in Practice

• Based on the NINDS trial, alteplase is approved for the treatment of stroke in the US up to 3 hours from symptom onset

• Alteplaseis approved up to 4.5 hours in Europe-The FDA evaluated this data but elected to not extend the approved window in the US

• Only 5-8% of patients receive alteplaseDO NOT

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Alteplase in CKD Patients with Acute Stroke

• CKD patients have generally not been excluded from acute stroke trials. Enrollment of patients on dialysis is very low which prohibits drawing meaningful conclusions.

• CKD patients are less likely to receive guideline concordant acute stroke care

• There is no dose adjustment based on renal function

Ovbiegele et al. Circ Cardiovasc QualOutcomes. 2014.

What about Outcomes?• There is some discrepancy among studies about

outcomes • A meta-analysis of 7 studies (7100 patients) found

increased symptomatic intracerebral hemorrhage (OR 1.56) and mortality (OR 1.7) among CKD patients treated with alteplase

• Among 44,410 alteplase treated patients in the GWTG registry:– 15,191 carried a CKD diagnosis– Higher unadjusted odds of sICH but this was attenuated by age,

hospital characteristics and risk factors– 22% higher odds of in-hospital mortality– 13% higher odds of unfavorable discharge functional status

Ovbiegele et al. Circ Cardiovasc QualOutcomes. 2014.Jung et al. J Neural Sci. 2015.DO N

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Alteplase in Dialysis Patients

• Very little data• Alteplase guidelines cite use of heparin within 48

hours with elevation in PTT as a contraindication– Is PTT a good marker here?

– K/DOQI guidelines (2005) suggest that this contraindication was not mean to apply to dialysis patients and advise considering each patient on a case by case basis

• A study of 1000 dialysis patients receving alteplasedid not find higher hemorrhage rates although in-hospital mortality was higher.

• There is still reluctance among stroke specialists…K/DOQI Workgroup, 2005.Tariq et al. JSCVD. 2013.Palacio et al. Clin Ja Am Soc Nephrol. 2011.

Alteplase in CKD Patient

• In patients who are treated with alteplase, the presence of CKD is likely associated with higher rates of hemorrhage and worse functional outcomes (observational data)

• In general, CKD should not be viewed as a contraindication to treatment

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Intra-arterial Therapies

Stroke Care Changed in 2015…

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And Again in 2018…

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What do the Guidelines Say?

• AHA guidelines recommend non-invasive vessel imaging for patients with suspected large vessel occlusion (IA recommendation)

• It is reasonable to proceed with CTA before obtaining a serum creatinine concentration for those without history of renal impairment (IIB recommendation)

Powers et al. Stroke. 2019.

Putting this into Practice-Under 6 Hours

• Most patients will still get a CTA

• Utility of CTP is less defined

• There is still a lot of information to be gained about endovascular suitability from the non-contrasted CT scan– Hyperdense Vessels– Early Ischemic

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Putting this into Practice-6-24 hours

• Patient selection is driven by the clinical exam first and foremost– NIH Stroke Scale

– Symptoms suggestive of large territory/cortical involvement

• Multimodal imaging including perfusion studies are necessary but only in the appropriate clinical setting

Considerations in CKD patients

• Is a CTA/CTP necessary?

• Renal Protection Measures– Fewer contrast runs

– Lower dose contrast

• Close hemodynamic monitoring during and following the procedure

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Outcomes in CKD Patients

• In a study of 628 patients (15% with renal impairment), there was a 47% lower likelihood of a good functional outcome

• A second recent study of 378 patients (31% CKD), similarly found a 46% lower likelihood of good functional outcome. – Mortality was also increased in CKD patients (OR 2.19)

– No difference on hemorrhagic complications

– The incidence of contrast associated AKI has been reported to be ~3%

Sutherland et al. JSCVD. 2020.Xiao et al. Neurology, 2019. Dipose et al. Stroke. 2019.

Closing Thoughts

• CKD is common in patients presenting with acute stroke– Presenting symptoms and patterns may differ

• Increasingly, contrasted studies are being used in acute management

• Outcomes following alteplase and endovascular therapy differ between CKD and non-CKD patients

• CKD is should not preclude patients from acute treatments but may help guide prognostication and inform shared decision makingDO N

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