- Highlights from the 14th annual Complex Cardiovascular Therapeutics: Advanced Endovascular and Coronary Intervention Global Summit (C3), Hilton Bonnet Creek, Orlando, FL, US, 17–20 June 2018 — Focus on acute stroke intervention.
Stroke is a leading cause of mortality worldwide, and may become an even greater burden with an aging population.1 Survival from acute stroke has increased over the past decades, largely due to greater understanding of the risk factors and adjustments in health education and intervention.2-4 However, a great deal of improvement remains to be made, and optimising the role of the cardiologist in stroke intervention is key.
Early intervention increases the likelihood of positive neurological outcomes;4 greater access to acute stroke intervention – to the same degree that percutaneous coronary intervention is available – may be key to improving outcomes further.5 Indeed, while a high proportion of first-time stroke patients in the US would be eligible for mechanical thrombectomy (MT), less than half the population has access to this service within one hour (the benchmark for early intervention),4 and one quarter of patients who are eligible for this intervention at transfer are no longer eligible at the point of admission.6 This highlights the need for effective, accessible, multi-disciplinary stroke teams across healthcare systems.
Key skills for cardiologists to develop further as they take an expanded role as stoke interventionalists include: accurate classification of the aortic arch (1,2, or 3) and appropriate selection of a catheter – almost all technical failures in intervention are due to complexities of the aortic arch.
Between a quarter and half of stroke patients have large vessel occlusions,7,8 and occlusion of the internal carotid artery or basilar artery are independently predictive of poor outcomes.8 Damage to the brain in stroke occurs as an infarct in the ‘core’, leading to irreversible damage, and as impaired blood flow in the surrounding penumbra, which places tissue at risk. The imaging ratio of core to penumbra (ideally small to relatively large) identifies patients who are likely to gain benefit from MT. The efficacy of endovascular intervention has been demonstrably tied to both how quickly intervention is made, as well as the type of imaging performed – the most positive outcomes used imaging to assess core–penumbra ratio,9,10 rather than traditional head computed tomography scans.11,12 While the benefit of immediate MT is clear, the benefit of this intervention after more than 6 hours was less certain; however benefits have been demonstrated at 16 hours (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3 [DEFUSE 3]) and up to 24 hours (Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention with Trevo [DAWN]) after the stroke event.13,14 These findings are now represented in the 2018 American Heart Association/American Stroke Association acute ischemic stroke guidelines.15
The potential role for direct carotid access in carotid and ischemic stroke intervention was discussed, focussing on key advantages, including:
Given the number of patients for whom treatment options in stroke are reduced over time with travel and delays in admission, the role of stroke interventions in the catheterisation laboratory is more relevant than ever. Intravenous tissue plasminogen activator (tPA) was recommended to be used in all acute ischaemic stroke patients within 3 hours post-symptom onset. This window can be extended to 4.5 hours, but should exclude patients as noted by the European Cooperative Acute Stroke Study (ECASS) III criteria.16 Intra-arterial lytics are not widely supported or approved in these patients currently, and thus should not be considered in most cases.
As noted earlier, MT has benefits in the 6-hour window and is efficacious in some patients up to 24-hours post-symptoms. MT is performed with either stent retrievers or aspiration devices; given that much of the evidence for the benefit of MT comes from studies using stent retrievers, guidelines support the use of these devices as first-line intervention. There is some support for using aspiration devices first in MT – they may be slightly quicker and cheaper. It was recommended that, in practice, the physician is familiar with both approaches as many patients will require crossover from one technique to the other to achieve optimal reperfusion. It was clearly shown that many complications arising from MT intervention can be mitigated if the physician performing the procedure is an expert – this is a crucial consideration in forming the multidisciplinary teams necessary for improving stroke outcomes in clinical practice.
Medical intervention in stroke management is a balance between reduced risk of stroke and increased risk of bleeding. Aspirin has demonstrated efficacy over the long term; however, intensification of anti-platelet treatment is often required, particularly in ST-elevation myocardial infarction (STEMI) patients.17
Clopidogrel in addition to aspirin is associated with a reduction in stroke incidence but an increase in bleeding, in both STEMI and non-STEMI patients.17 These findings were explored further in the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) study, which showed that in patients with minor stroke who can be treated within 24 hours, clopidogrel addition to aspirin reduced risk of stroke in the first 90 days without increased risk of haemorrhage.18 However, there are concerns around whether findings in this highly selective study population can be generalised to a wider patient population. The recent Platelet-Oriented Inhibition In New TIA and Minor Ischemic Stroke (POINT) study observed that, in patients from diverse countries with minor ischemic stroke or high-risk transient ischaemic stroke, the combination of clopidogrel and aspirin was associated with lower risk of a composite endpoint of ischemic stroke, myocardial infarction, or death from ischemic vascular causes, but had a higher risk of major haemorrhage compared with aspirin alone.19 The Rivaroxaban for the Prevention of Major Cardiovascular Events in Coronary or Peripheral Artery Disease (COMPASS) trial examined the addition of rivaroxaban to aspirin in patients with stable atherosclerotic vascular disease.20 While rivaroxaban alone offered no cardiovascular benefit versus aspirin alone, the combination was associated with reduced ischemic stroke by 49%, without a significant increase in intracranial haemorrhage or haemorrhagic conversion.20 It was noted that the reduced incidence of stroke lead to a reduction in measurable early disability, and that this intervention was of value in the management of patients with stable atherosclerotic vascular disease and no atrial fibrillation.
1. Ingall T. Stroke--incidence, mortality, morbidity and risk. J Insur Med. 2004;36:143–52.
2. Lackland DT, Roccella EJ, Deutsch AF, et al. Factors influencing the decline in stroke mortality: a statement from the American Heart Association/American Stroke Association. Stroke. 2014;45:315–53.
3. Lee S, Shafe AC, Cowie MR. UK stroke incidence, mortality and cardiovascular risk management 1999-2008: time-trend analysis from the General Practice Research Database. BMJ Open. 2011;1:e000269.
4. Koton S, Schneider AL, Rosamond WD, et al. Stroke incidence and mortality trends in US communities, 1987 to 2011. JAMA. 2014;312:259–68.
5. Widimsky P. When will acute stroke interventions be as widely available as primary PCI? EuroIntervention. 2017;13:1269–72.
6. Nikoubashman O, Pauli F, Schürmann K, et al. Transfer of stroke patients impairs eligibility for endovascular stroke treatment. J Neuroradiol. 2018;45:49–53.
7. Puetz V, Dzialowski I, Coutts SB, et al. Frequency and clinical course of stroke and transient ischemic attack patients with intracranial nonocclusive thrombus on computed tomographic angiography. Stroke. 2009;40:193–9.
8. Smith WS, Lev MH, English JD, et al. Significance of large vessel intracranial occlusion causing acute ischemic stroke and TIA. Stroke. 2009;40:3834–40.
9. Campbell BC, Mitchell PJ, Kleinig TJ, et al. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med. 2015;372:1009–18.
10. Menjot de Champfleur N, Saver JL, Goyal M, et al. Efficacy of stent-retriever thrombectomy in magnetic resonance imaging versus computed tomographic perfusion-selected patients in SWIFT PRIME trial (solitaire FR with the intention for thrombectomy as primary endovascular treatment for acute ischemic stroke). Stroke. 2017;48:1560–6.
11. Berkhemer OA, Fransen PS, Beumer D, et al. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med. 2015;372:11–20.
12. Jovin TG, Chamorro A, Cobo E, et al. Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med. 2015;372:2296–306.
13. Albers GW, Marks MP, Kemp S, et al. Thrombectomy for stroke at 6 to 16 hours with selection by perfusion imaging. N Engl J Med. 2018;378:708–18.
14. Nogueira RG, Jadhav AP, Haussen DC, et al. Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct. N Engl J Med. 2018;378:11–21.
15. Powers WJ, Rabinstein AA, Ackerson T, et al. 2018 Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2018;49:e46–e110.
16. Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008;359:1317–29.
17. Tran H, Mehta SR, Eikelboom JW. Clinical update on the therapeutic use of clopidogrel: treatment of acute ST-segment elevation myocardial infarction (STEMI). Vasc Health Risk Manag. 2006;2:379–87.
18. Wang Y, Wang Y, Zhao X, et al. Clopidogrel with aspirin in acute minor stroke or transient ischemic attack. N Engl J Med. 2013;369:11–9.
19. Johnston SC, Easton JD, Farrant M, et al. Clopidogrel and aspirin in acute ischemic stroke and high-risk TIA. N Engl J Med. 2018;379:215–25.
20. Eikelboom JW, Connolly SJ, Bosch J, et al. Rivaroxaban with or without aspirin in stable cardiovascular disease. N Engl J Med. 2017;377:1319–30.