Stent-Protected Angioplasty in Asymptomatic Carotid Artery Stenosis vs. Endarterectomy: SPACE2 – a Three-Arm Randomised-Controlled Clinical Trial

Abstract

Moderate to severe (> or =70%) asymptomatic stenosis of the extracranial carotid artery leads to an increased rate of stroke of approximately 11% in 5 years. Patients with asymptomatic carotid stenosis, however, are also at a higher risk of nonstroke vascular events. The estimated annual risks of such events in patients with asymptomatic stenosis are 7% for a coronary ischaemic event and 4-7% for overall mortality. The superiority of carotid endarterectomy compared with medical treatment in symptomatic carotid disease is established, provided that the surgical procedure can be performed with a perioperative morbidity and mortality of <6%. The advantage of carotid endarterectomy for asymptomatic patients is less established. An alternative treatment, carotid artery stenting, has been developed. This treatment is used frequently in both symptomatic and asymptomatic patients. In the last decade, major advantages in medical primary prevention of cerebrovascular and cardiovascular disease have been accomplished. The control groups in the large trials for asymptomatic carotid artery disease (ACAS and ACST) originate from more than a decade ago and, for the most part, have not received a medical primary prevention strategy that would now be considered the standard according to current national and international guidelines. For this reason, a three-arm trial (SPACE2; http://www.space-2.de) with a hierarchical design and a recruitment target of 3640 patients is chosen. Firstly, a superior trial of intervention (carotid artery stenting or carotid endarterectomy) vs. state-of-the-art conservative treatment is designed. In case of superiority of the interventions, a noninferiority end-point will be tested between carotid artery stenting and carotid endarterectomy. This trial is registered at Current Controlled Trials ISRCTN 78592017.

Response to Letters by Reiff et al and Hadjiev and Mineva

“…Seventy percent to 80% of carotid interventions in the United States are performed for asymptomatic disease, which may provide the patient with minimal or no benefit over medical management. We could not agree more that there is a desperate need for a contemporary, prospective, randomized study that compares intervention whether it be carotid endarterectomy, carotid angioplasty, and stenting, or both, like in Stent-Protected Angioplasty in Asymptomatic Carotid Artery Stenosis (SPACE-2), 2 to best medical management for asymptomatic carotid artery stenosis. We sincerely apologize for being unaware of the SPACE-2 trial and we thank the authors for bringing this important trial to our attention.…”

Asymptomatic carotid artery stenosis: time to rethink our therapeutic options?

“…The Stent-Protected Angioplasty in Asymptomatic Carotid Artery Stenosis versus Endarterectomy (SPACE-2) study is a 3-arm study that aims to recruit more than 3500 patients and randomly assign them to medical therapy alone or invasive treatment with CEA or CAS. 37 Another ongoing trial is the Aggressive Medical Treatment Evaluation for Asymptomatic Carotid Artery Stenosis (AMTEC), which will also compare contemporary medical treatment to CEA. 22 The CREST investigators in North America are also in the advanced planning phase of a similar study although the details have not been completely defined yet.…”

Behandlung asymptomatischer Karotisstenosen

“…Sollte die invasive Therapie überlegen sein, wäre als sekundäre Analyse der Vergleich zwischen CEA und Stenting gefolgt [6]. Aufgrund der relativ geringen zu erwartenden Schlaganfallrate wurde diese Studie für mehr als 3000 Patienten und eine Mindestbeobachtungszeit von fünf Jahren geplant.…”