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Systematic review and meta-analysis of perioperative and long-term outcomes in patients receiving statin therapy before carotid endarterectomy

  • Review Article - Vascular Neurosurgery - Other
  • Published:
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Abstract

Background

Carotid endarterectomy (CEA) is associated with perioperative stroke and mortality in a minority of cases. The aim of this systematic review and meta-analysis was to investigate the effect of pre-operative statins on perioperative outcomes in patients undergoing CEA for internal carotid artery (ICA) stenosis.

Methods

A systematic review of PubMed, Medline, and the Cochrane Database of Systematic Reviews was performed. Studies were included which reported perioperative stroke and/or survival outcomes following CEA for ICA stenosis and compared patients who were and were not taking pre-operative statins. Relevant data were extracted and pooled using meta-analysis.

Results

Seven studies met the inclusion criteria, comprising 21,387 patients. A total of 68.9% (14,976) were administered statins and 31.1% (6657) were statin-free. Pre-operative statin use was higher in patients with a history of cardiac disease (12.2 vs. 23.6% in the statin-free group), diabetes (31.6 vs. 25.1% in the statin-free group), and hypertension (83.5 vs. 72.2% in the statin-free group), while a greater proportion of statin-free patients had symptomatic disease (44.9 vs. 55.5% in the statin-free group). Statins were associated with reduced perioperative stroke in all patients (OR 0.57; 95% CI 0.34–0.95; p = 0.03) and in symptomatic patients (OR 0.57; 95% CI 0.35–0.93; p = 0.03). A trend towards lower perioperative mortality (OR 0.54; 95% CI 0.29, 1.03; p = 0.06) and significantly improved overall survival was observed in the statin group (HR 0.69; 95% CI 0.59–0.81; p < 0.001) at a mean follow-up of 62 months (range 27–76 months).

Conclusions

Administration of statins before CEA is associated with lower rates of perioperative stroke and improved overall survival. Compliance with optimal medical treatment associated with the use of pre-operative statins may limit the clinical significance of these findings. Future investigation to characterize the potential benefit of statin therapy in patients undergoing CEA for ICA stenosis is warranted.

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Authors and Affiliations

  1. Department of Neurological Surgery, Columbia University Medical Center, New York, NY, USA

    Natasha Ironside, Daniel Brenner, Eric Heyer, Trae Robison, Brandon Christophe & Edward Sander Connolly

  2. Department of Neurological Surgery, University of Virginia Health System, Charlottesville, VA, USA

    Ching-Jen Chen

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  1. Natasha Ironside
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Correspondence to Natasha Ironside.

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All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge, or beliefs) in the subject matter or materials discussed in this manuscript.

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We have here a scholarly analysis of seven published studies where CEA patients either were or were not on statin therapy prior to surgery. The hypothesis would be that it is better to be taking a statin when surgery is done, to prevent stroke or other vascular morbidity. And, indeed, these authors confirm this, that is, administration of statin therapy before carotid endarterectomy is associated with lower rates of perioperative stroke. This is useful information to allow us to optimize perioperative CEA care.

This being said, there are limitations. This is a retrospective meta-analysis of data published by other groups. The authors themselves do not offer us any of their patients in the review. In addition, this means that patients were on statin therapy (or not) for different reasons that prevention of stroke at surgery. The observation that stroke rates are reduced is just that, an observation of an epiphenomenon, rather than the testing of a hypothesis in a controlled trial of statins and CEA (which would be the ideal way).

The authors’ own conclusions need no embellishment and are worth repeating here, since the data is important and the article is a long one:

“Among the seven studies identified, 69% of patients were administered statin therapy and 31% were statin-free prior to CEA. The statin therapy group experienced lower rates of perioperative stroke in all patients (2.4% versus 3.0% in the statin-free group, p = 0.03) and in those with symptomatic disease (1.6% vs. 3.3% in the statin-free group, p = 0.03). Improved survival was also observed in the statin therapy group (HR 0.67; 95% C.I. 0.59, 0.81; p<0.0001) at a mean follow-up duration of 62 months.”

As we would have predicted, this meta-analysis showed that a greater proportion of perioperative stroke events occurred among symptomatic patients (2.5 vs. 1.4% in the asymptomatic group, p = 0.01). But, importantly, the use of statins seemed to offer a protection; within this at-risk cohort, rates of perioperative stroke events were lower in the statin therapy group (1.6 vs. 3.3% in the statin-free group, p = 0.03), lending further strength to the hypothesis that statin therapy may exert a protective effect, in the perioperative period, among patients undergoing CEA.

We can conclude that a milieu of concomitant statin use affords a protection against vascular events at the time of CEA, especially in symptomatic carotid disease. The next step is a randomized trial, which would be easy to do and would offer tremendous benefit in optimizing CEA care.

Christopher M. Loftus

Philadelphia, PA, USA

This article is part of the Topical Collection on Vascular Neurosurgery

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Ironside, N., Brenner, D., Heyer, E. et al. Systematic review and meta-analysis of perioperative and long-term outcomes in patients receiving statin therapy before carotid endarterectomy. Acta Neurochir 160, 1761–1771 (2018). https://doi.org/10.1007/s00701-018-3618-5

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  • DOI: https://doi.org/10.1007/s00701-018-3618-5

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