Age effect in Asymptomatic Carotid Stenosis in the CREST and ACT 1 Stenting versus Endarterectomy Trials.

Objective: We assessed if age was an effect modifier in a pooled analysis of two randomized trials comparing CAS and CEA in asymptomatic patients, CREST and ACT I.

Methods: We analyzed data from 2544 patients aged <80 with ≥70% asymptomatic carotid stenosis randomized to CAS or CEA (n=1091; n=1453) who were recruited between 2000 and 2013. Age was considered in four strata (<65, 65-69, 70-74 and 75-79). The primary outcome was any stroke, myocardial infarction or death during the peri-procedural period, or ipsilateral stroke afterwards. The secondary outcome of any stroke or death during the peri-procedural period or ipsilateral stroke within 4 years was also analyzed.

Results: For the primary outcome, there were no CAS-versus-CEA treatment differences within any age stratum (p > 0.05). For the secondary outcome of stroke-or-death, those randomized to CAS age 75-79 were at approximately four-times greater risk compared to those randomized to CEA (10% vs 2%%, HR = 4.41; 95% CI: 1.31-14.83). No treatment differences between CAS and CEA were detected for the three younger age strata, <65, 65-69 and 70-74 (p>0.05). For patients randomized to CAS, the risk of the primary endpoint for those aged 75-79 was higher than the risk for those age <65 (11% vs 4%, HR = 2.90; 95% CI: 1.52-5.53), without significant differences between other strata (p > 0.05). For those randomized to CEA, there were no differences between age strata ((p > 0.1)).

Conclusion: This pooled analysis of 2544 asymptomatic patients in CREST and ACT-1 shows a higher stroke-or-death risk for CAS compared to CEA in only the oldest age group, 75-79. For patients randomized to CAS, there was an increased risk for patients aged 75-79. No increased risk by age was found for patients randomized to CEA. Hence, the clinical management of asymptomatic patients above age 75 must be individualized, to optimize outcomes in the context of advances in CAS since 2013.