Statin Neuroprotection and Carotid Endarterectomy: Safety, Feasibility and Outcomes

• Status: Recruiting
• Trial end date: 2022-04-01
• Target enrollment: 0
• Participant gender: All

Summary

The investigators hypothesize that pre-operative statin use is neuroprotective at maximal doses. The goals are to determine the safety, feasibility, and efficacy of maximizing statin doses for two weeks (12-18 days) prior to CEA using change in performance on a battery neuropsychometric tests as outcome measure. Study will recruit patients based on their preexisting statin regimen.

The investigators hypothesize that in asymptomatic CEA patients: 1) Pre-operative statin use is neuroprotective against early cognitive dysfunction (eCD) and lowers the risk of early mortality. 2) Maximal doses may be essential in achieving optimal neuroprotection against eCD.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Columbia University
• Treatments: Atorvastatin; Atorvastatin Calcium; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium; Simvastatin

Criteria

Inclusion Criteria:

1. Age ≥ 18 years of age.

2. Patient is currently on atorvastatin or simvastatin or rosuvastatin or statin naïve (no statins in the last 30 days).

3. The patient has unilateral or bilateral carotid artery stenosis that is considered severe (carotid artery diameter reduction ≥ 70%) as defined by:

1. Peak systolic velocity of at least 230 cm/s plus at least one of these:

2. End diastolic velocity ≥ 100 cm/s OR

3. CTA showing ≥ 70% stenosis OR

4. MRA showing ≥ 70% stenosis

4. This stenosis has not caused any stroke, transient cerebral ischemia, or other relevant neurological symptoms in the past.

5. The patient's attending doctor(s) (PMD, cardiologist, vascular/neurosurgeon) AND the patient have decided to proceed with a CEA to treat the patient's severe carotid stenosis.

6. The patient has no known circumstance or condition likely to preclude 1 year follow-up or adherence to the study protocol.

7. The patient is independent in their Activities of Daily Living at baseline.

8. Patient has the ability to provide informed consent.

Exclusion Criteria:

1. Patient has underlying disease other than atherosclerosis (i.e. autoimmune disease, known active malignancy).

2. Patient has documented dementia or screens out based on abnormal Baseline MoCA (≤25) and AD8 (≥2).

3. Patient's life expectancy is < 12 months.

4. Patient has advanced renal failure (serum creatinine > 2.5 mg/dL)

5. Patient has evidence of severe congestive heart failure or has history of end-stage cardiovascular disease (e.g. CHF NYHA Class III or IV or unstable angina).

6. Patient has history of intolerance or allergic reaction to any statins (myotoxicity, hepatic dysfunction, rash, etc.)

7. Patient has received an investigational drug within 30 days.

8. Patient is pregnant or lactating.

9. Patient is currently taking any of the following which have been shown to interact with atorvastatin and/or simvastatin and/or rosuvastatin (as per current drug package inserts):

• Cyclosporine;

• HIV Protease Inhibitors/Antivirals (e.g. rotanavir or plus rotanavir, tipranavir, lopinavir, boceprevir, saquinovir, darunavir, fosamprenavir, nelfinavir, efavirenz/tenofobir, atazanavir, simeprevir);

• Hep C Protease Inhibitor/Antivirals (e.g. telapravir);

• Antibiotics (i.e. cobicistat-containing products like Tybost, rifampin/rifampicin, clarithromycin, telithromycin, erythromycin);

• Anti-fungals (i.e. itraconazole, ketoconazole, posaconazole, voriconazole, fluconazole); *Gemfibrozil; Other Fenofibrates (e.g. Tricor, fibric acid);

• Niacin > 1g/day or statins in combination with niacin (e.g. Vytorin, Simcor);

• Colchicine;

• Danazol;

• Calcium Channel Blockers: Diltiazem, Varapamil;

• Dronedarone;

• Amiodarone;

• Digoxin;

• Ranolazine;

• Nefazodone;

• Warfarin/Coumadin;

• Lomitapide;

• Grapefruit juice > 1.2 liters/day (40.5 ounces/day).