Effect of Extended-Release Niacin on Saphenous Vein Graft Atherosclerosis (ALPINE-SVG)

Veterans Affairs (VA) North Texas Health Care System

Status and phase

Completed

Phase 2

Conditions

Intermediate Saphenous Vein Graft Lesions

Aortocoronary Saphenous Vein Bypass Graft Atherosclerosis

Treatments

Drug: extended-release niacin (Niaspan)

Study type

Interventional

Funder types

Other U.S. Federal agency

NIH

Identifiers

NCT01221402

10-029

R01HL102442 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

Intermediate saphenous vein graft (SVG) lesions are common, have high rates of progression to severe lesions or occlusion, and are associated with high incidence of adverse clinical outcomes.

The ALPINE-SVG trial is a randomized-controlled trial of extended-release niacin vs. placebo in patients with intermediate saphenous vein graft lesions. The main hypothesis of the study is that compared to placebo, niacin administration will result in reduction in percent atheroma volume at 12-month follow-up angiography.

Full description

This is a phase II, single-center, double-blind trial that will randomize 138 prior CABG patients with an intermediate SVG lesion (30%-60% angiographic diameter stenosis) on clinically-indicated coronary angiography, and HDL-C<60 mg/dL to ER-niacin at a dose of 1500-2000 mg daily or matching placebo (containing 50 mg of niacin that can cause flushing but has no lipid lowering effect) for 12 months. All patients will receive a statin with goal LDL-C <70 mg/dL. Coronary angiography, intravascular ultrasonography (IVUS), and intravascular near-infrared intracoronary spectroscopy (NIRS), and optical coherence tomography (OCT) of the intermediate SVG lesion will be performed at enrollment and after 12 months in each patient, along with exercise stress testing at 1 month and 12 months, B-mode carotid ultrasound imaging at enrollment and after 6 and 12 months, reactive hyperemia peripheral arterial tonometry (RH-PAT) at enrollment and after 6 and 12 months, and with peripheral blood sampling performed at enrollment and at 1, 3, 6, 9 and 12 months, to determine whether compared to placebo, administration of ER-niacin will result in:

Reduction of the percent atheroma volume (PAV) of the intermediate SVG lesion at 12-month follow-up IVUS imaging (primary endpoint)
Reduction of total and normalized total intermediate SVG lesion atheroma volume, reduction of atheroma volume in the most diseased 10-mm subsegment of the target intermediate lesion, reduction of atheroma volume in the subsegment of the target intermediate lesion with lipid core plaque by NIRS, reduction of lipid core burden index as assessed by near-infrared intracoronary spectroscopy, increase in fibrous cap thickness and reduction in the prevalence and number of microchannels, in the presence and extent of necrotic lipid pool, plaque rupture, calcification, and thrombus, as assessed by optical coherence tomography, and reduction of angiographic intermediate SVG target lesion failure at 12-month follow-up SVG imaging (secondary endpoints)
Increased exercise capacity and reduction in ischemia, as assessed by exercise stress testing between 1 and 12 months (secondary endpoint)
Less increase in mean carotid intima-media thickness at 6 and 12 months (secondary endpoint)
Greater increase in natural logarithmic scaled reactive hyperemia index (L_RHI) at 6 and 12 months (secondary endpoint)
Greater increase in EPC-CFU/mL of peripheral blood from baseline to 1, 3, 6, and 12 months post enrollment (secondary endpoint)
Reduction of major adverse cardiac events (defined as the composite of death, acute coronary syndrome, or coronary revascularization) during follow-up (secondary endpoint)

Enrollment

38 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Age 18 years or greater
Willing and able to give informed consent. The patients must be able to comply with study procedures and follow-up.
Undergoing clinically-indicated coronary and SVG angiography
Have an intermediate SVG lesion (defined as a lesion 30-60% angiographic diameter stenosis) without previous percutaneous intervention, amenable to examination with IVUS. The lesion should have no thrombus or ulceration and should not be considered responsible for the patient's clinical presentation and referral for graft angiography.

Exclusion criteria

Known allergy to niacin
History of statin-induced myopathy
Positive pregnancy test or breast-feeding
Coexisting conditions that limit life expectancy to less than 12 months or that could affect a patient's compliance with the protocol
Uncontrolled fasting triglyceride levels ( 500 mg/dL)
Fasting LDL-C >200 mg/dL
Fasting HDL-C >60 mg/dL
Poorly controlled diabetes (glycosylated hemoglobin levels 10%)
Current active liver disease or hepatic dysfunction
AST or ALT > 2x the upper limit of normal
Uncontrolled hypothyroidism (Thyroid Stimulating Hormone >1.5 x upper limit of normal [ULN])
Unexplained creatine kinase elevations (>3 x ULN)
Recent history of acute gout
Serum creatinine > 2.5 mg/dL
HIV (due to potential anti-retroviral drug-interactions with niacin)
Use of high-dose, antioxidant vitamins (vitamins C, E, or beta-carotene) that may interfere with the HDL-raising effect of niacin
Severe peripheral arterial disease limiting vascular access
Referral for cardiac catheterization by a physician who is an investigator in the present study.
Symptoms consistent with moderate or greater severity of congestive heart failure (New York Heart Association - NYHA class III or IV) or whose most recent determination of left ventricular ejection fraction is <25%
Uncontrolled hypertension, defined as either a resting diastolic blood pressure of ≥100 mmHg or a resting systolic blood pressure of ≥200 mmHg
History of allergic reaction to iodine-based contrast agents
Significant medical or psychological condition that, in the opinion of the investigator, may compromise the patient's safety or successful participation in the study