One of the largest randomised trials to examine the effectiveness of two stroke-prevention procedures for clearing blocked neck arteries (carotid stenosis) suggests that women are at more than double the short-term risk of stroke following carotid stenting compared with traditional surgery to remove the inner lining of the diseased blood vessel (endarterectomy). In contrast, little difference in stroke risk was noted between the procedures in men. The findings, published Online First in The Lancet Neurology, suggest that the sex of a patient might be an important consideration when choosing treatment options for carotid disease.
People with blockages in the carotid artery that supplies blood to the brain are at a high risk of stroke. Although women bear the greatest burden from stroke they have been underrepresented in trials, and there is a lack of information to guide which stroke-prevention procedures might be most effective in women.
The CREST trial was established to compare the safety and effectiveness* of endarterectomy and carotid stenting in patients who had experienced a minor stroke (transient ischaemic attack) or had no pre-existing symptoms but showed a narrowing of the carotid artery. Between December 2000 and July 2008, 2502 patients were recruited from 117 centres across the USA and Canada. The study was funded by the US National Institutes of Health.
In 2010, initial results showed that the overall safety and efficacy of the two interventions were similar, although more heart attacks were noted in the surgical group and more strokes in the stenting group.
In this study, Virginia Howard from the University of Alabama in Birmingham, Alabama, USA, Thomas Brott from the Mayo Clinic, Florida, USA and colleagues report the sex-specific subgroup analyses (the potential treatment differences between the sexes) and examine whether the risks between stenting and surgery are shared equally by men and women.
In the first 30 days following the procedures, stroke, heart attack, and death were more frequent in women who had stenting than in those who had surgery (6.8% vs 3.8%), whereas the rates were similar after the two procedures in men (4.3% vs 4.9%).
This sex difference was mainly the result of a significantly higher likelihood of stroke in women after stenting compared with surgery (5.5% vs 2.2%), whereas the post-operative risk of stroke did not significantly differ by procedure in men (3.3% vs 2.4%).
The authors say: "Although there was no evidence of a relative difference in the 4-year primary composite outcome by sex, the periprocedural stroke risk for women in the carotid artery stenting group was more than twice the risk of those in the carotid endarterectomy group, whereas there was little difference in men."
They conclude: "This study adds to previous findings by showing a higher periprocedural risk from carotid artery stenting in women…This additional information supports that the sex of the patients should be taken into account in decisions for treatment of carotid disease."
In a Comment, Martin Brown and Rosalind Raine from University College London, London, UK, caution: "Any differential effects of treatment by sex are unlikely to be explained by differences in sex chromosomes. Far more likely is that other patient characteristics are the true determinants of risk difference"
They add: "The choice of treatment between the sexes therefore requires better understanding of the various predictors of risk. Future work needs to concentrate on identifying these risk factors to select which of carotid stenting, carotid endarterectomy, or optimised medical therapy are most appropriate for which women and which men."
Professor Thomas Brott, Mayo Clinic, Florida, USA. T) +1 904 953 0556 E) brott.thomas@mayo.edu
Associate Professor Virginia Howard, University of Alabama at Birmingham, Birmingham, Alabama, USA. T) +1 205 934 7197 E) VHoward@ms.soph.uab.edu
Professor Martin Brown, University College London, London, UK. E) m.brown@ion.ucl.ac.uk
Notes to Editors:
*As measured by the occurrence of stroke, heart attack, or death from any cause within 30 days of the procedure (periprocedural period), or strokes on the side of the brain with carotid blockage (ipsilateral stroke) within 4 years of randomisation.
NOTE: IF YOU WISH TO PROVIDE A LINK TO THE FREE ABSTRACT OF THIS PAPER FOR YOUR READERS, PLEASE USE THE FOLLOWING, WHICH WILL GO LIVE AT THE TIME THE EMBARGO LIFTS:
http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(11)70080-1/abstract
Journal
The Lancet Neurology