Rationale Trials conducted decades ago demonstrated that
carotid endarterectomy by skilled surgeons reduced
stroke risk in asymptomatic patients. Developments in carotid stenting and improvements in medical prevention of
stroke caused by atherothrombotic disease challenge understanding of the benefits of revascularization. Aim Carotid Revascularization and Medical Management for Asymptomatic
Carotid Stenosis Trial (CREST-2) will test whether
carotid endarterectomy or carotid stenting plus contemporary intensive medical
therapy is superior to intensive medical
therapy alone in the primary prevention of
stroke in patients with high-grade asymptomatic
carotid stenosis. Methods and design CREST-2 is two multicenter randomized trials of revascularization plus intensive medical
therapy versus intensive medical
therapy alone. One trial randomizes patients to
carotid endarterectomy plus intensive medical
therapy versus intensive medical
therapy alone; the other, to carotid stenting plus intensive medical
therapy versus intensive medical
therapy alone. The risk factor targets of centrally directed intensive medical
therapy are
LDL cholesterol <70 mg/dl and systolic blood pressure <140 mmHg. Study outcomes The primary outcome is the composite of
stroke and death within 44 days following randomization and
stroke ipsilateral to the target vessel thereafter, up to four years. Change in cognition and differences in major and minor
stroke are secondary outcomes. Sample size Enrollment of 1240 patients in each trial provides 85% power to detect a treatment difference if the event rate in the intensive medical
therapy alone arm is 4.8% higher or 2.8% lower than an anticipated 3.6% rate in the revascularization arm. Discussion Management of asymptomatic
carotid stenosis requires contemporary randomized trials to address whether
carotid endarterectomy or carotid stenting plus intensive medical
therapy is superior in preventing
stroke beyond intensive medical
therapy alone. Whether
carotid endarterectomy or carotid stenting has favorable effects on cognition will also be tested. Trial registration United States National Institutes of Health Clinicaltrials.gov NCT02089217.