What is the stroke rate in patients with carotid stenosis on optimal medical management, as inferred from the CREST 2 trial?

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Stroke Rate in CREST-2 Medical Management Arm

In the CREST-2 trial, patients with asymptomatic high-grade carotid stenosis (≥70%) managed with intensive medical therapy alone had a 4-year stroke rate of 5.3% in the endarterectomy trial and 6.0% in the stenting trial, translating to approximately 1.3-1.5% annually. 1

CREST-2 Medical Management Outcomes

Primary Endpoint Results

  • Endarterectomy trial: The medical-therapy group had a 4-year incidence of stroke or death (0-44 days) or ipsilateral ischemic stroke (thereafter) of 5.3% (95% CI, 3.3-7.4%) 1
  • Stenting trial: The medical-therapy group had a 4-year incidence of the same composite endpoint of 6.0% (95% CI, 3.8-8.3%) 1

Early Periprocedural Period (0-44 Days)

  • In the endarterectomy trial: 3 strokes occurred in the medical-therapy group during the first 44 days 1
  • In the stenting trial: 0 strokes or deaths occurred in the medical-therapy group during the first 44 days 1

Annual Stroke Rate Calculation

  • The 4-year rates of 5.3-6.0% translate to an approximate annual stroke rate of 1.3-1.5% in patients receiving intensive medical management 1
  • This aligns with contemporary data showing annual stroke rates in medically treated asymptomatic carotid stenosis patients have fallen to ≤1% per year 2

CREST-2 Intensive Medical Management Protocol

Core Components

  • Aspirin 325 mg daily as the antiplatelet agent 3
  • Systolic blood pressure target <130 mmHg (initially <140 mmHg, then revised) 3
  • LDL cholesterol target <70 mg/dL 3
  • Secondary targets: tobacco cessation, non-HDL control, HbA1c optimization, physical activity, and weight management 3

Risk Factor Control Achievement

  • LDL cholesterol: Improved from mean baseline of 80.5 mg/dL to 66.7 mg/dL, with 67% of patients achieving target <70 mg/dL 3
  • Systolic blood pressure: Improved from mean baseline of 139.7 mmHg to 130.3 mmHg, with 61% achieving target <130 mmHg 3
  • Both improvements were statistically significant (P<0.001) 3

Clinical Context and Comparison

Historical Perspective

  • The CREST-2 results demonstrate dramatically lower stroke rates compared to older trials like ACAS (1990s), where medical therapy alone resulted in an 11% 5-year stroke rate (approximately 2.2% annually) 2
  • This 60-70% decline in stroke rates from 1995-2010 was attributed to better medical treatment and lower smoking incidence 4

Comparison to Revascularization

  • Stenting plus medical therapy: 4-year stroke rate of 2.8% (P=0.02 compared to medical therapy alone) 1
  • Endarterectomy plus medical therapy: 4-year stroke rate of 3.7% (P=0.24, not statistically significant compared to medical therapy alone) 1

Important Caveat

  • The periprocedural period (0-44 days) showed 7 strokes and 1 death in the stenting group versus 0 events in the medical-therapy group in the stenting trial 1
  • In the endarterectomy trial, 9 strokes occurred in the endarterectomy group versus 3 in the medical-therapy group during the periprocedural period 1

Key Takeaway for Clinical Practice

The CREST-2 trial definitively demonstrates that contemporary intensive medical management achieves annual stroke rates of approximately 1.3-1.5% in asymptomatic high-grade carotid stenosis, which is substantially lower than historical medical therapy outcomes and challenges the routine use of revascularization in this population. 1

References

2
Guideline

Stroke Risk in Asymptomatic Severe Carotid Stenosis: Medical Therapy vs. Intervention

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

4
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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