Valsartan for Suppression of Plaque Volume and Restenosis After Drug-Eluting Stent

Study Overview
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Brief Summary
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To evaluate that angiotensin-converting enzyme (ACE) inhibitors and angiotensin-converting enzyme receptor blockers (ARBs) reduce the risk of restenosis after DES implantation.

Detailed Description
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Stimulation of the angiotensin II type 1 (AT1) receptors after arterial injury promotes vascular smooth muscle cell (VSMC) migration, proliferation, and extracellular matrix production, leading to the hope that blockade of this receptor by angiotensin-converting enzyme inhibitors (ACEI) or specific (AT1) receptor antagonists (ARBs) might reduce intimal hyperplasia. However, despite confirmatory evidence in several animal models of restenosis, the large scale MERCATOR and MARCATOR trials of cilazapril with balloon angioplasty failed to show benefit. In 1999, Kondo reported the results of a randomized pilot trial of 100 patients who received Palmaz-Schatz stents and were randomized to receive the ACE inhibitor quinapril or placebo. The volume of neointimal hyperplasia assessed by IVUS was significantly less quinapril than the control group (18 ± 0.6 mm3 vs. 25 ± 0.6 mm3; p < 0.05). The quinapril group's restenosis rate was 16%, with the quinapril benefit being observed only in patients with the D/D and I/D genotypes. Also, other study reported on a consecutively treated cohort of 1,598 stented patients, noting that ACE inhibitor usage at the time and after stenting reduced the risk of subsequent revascularization dramatically (adjusted odds ratio, 0.46; p = 0.001). In the ValPREST trial which is a single-center randomized trial of patients receiving stents for type B2/C lesions, comparing valsartan (and ARV) 80 mgs daily with open treatment, patients randomized to valsartan had a 19% incidence of restenosis compared with 39% in the open treatment arm (p = 0.005). Recently, several randomized studies were conducted to compare the safety and efficacy of the two leading drug-eluting stent (DES). However, data on the association of ARBs for suppression of neointimal hyperplasia are limited in the DES era. Therefore, a pivotal randomized study is warranted.

Official Title
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Valsartan for SUPpression of Plaque Volume and Restenosis After Drug-Eluting Stent (The VAL-SUPPRESS TRial)

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Drug: Valsartan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical 1) Patients with angina and documented ischemia or patients with documented silent ischemia 2) Patients who are eligible for intracoronary stenting 3) Age >18 years, <75 ages 4) Preserved left ventricular ejection fraction (>40%) 5) Written informed consent to the study protocol 6) Patients with hemodynamic stability and appropriate blood pressure, which were suitable for administration of valsartan 160mg Angiographic: Patients who have 1) Significant ischemic narrowing (target vessel) De novo coronary lesion (no restriction of lesion length) Percent diameter stenosis ≥50% by visual estimate Reference vessel size ≥2.5 mm by visual estimation Lesions suitable for stenting And/Or 2) Non-significant non-ischemic intermediate narrowing (non-target vessel) Percent diameter stenosis 20% 50% by visual estimate No objective evidence of ischemia Exclusion Criteria: Patients received a Angiotensin converting enzyme inhibitor (ACE-I) or ACE-receptor blockers (ARBs) in the previous week prior to enrollment History of bleeding diathesis or coagulopathy Pregnant Known hypersensitivity or contra-indication to contrast agent and heparin Limited life-expectancy (less than 1 year) Acute ST-elevation myocardial within 1 week Characteristics of lesion 1) Left main disease 2) In-stent restenosis 3) Graft vessels Hematological disease (Neutropenia <3000/mm3, Thrombocytopenia <100,000/mm3) Hepatic dysfunction, liver enzyme (ALT and AST) elevation >3 times normal Renal dysfunction, creatinine >2.0mg/dL Contraindication to aspirin and clopidogrel

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Valsartan treatment gorup<br>Valsartan 160mg per day group | Drug: Valsartan<br>* Valsartan 160mg per day<br>|
| No Intervention: No Valsartan treatment group<br>No valsartan treatment | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Angiographic in-stent late-loss (target vessel) |  | at 8-month follow-up. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of Major cardiac adverse events including death, Q-MI, Non Q-MI, and target lesion or vessel revascularization -Delta change in percent atheroma area and volume |  | 30 days | 
| Composite of Major cardiac adverse events including death, Q-MI, Non Q-MI, and target lesion or vessel revascularization |  | 9 months | 
| Each component of MACE | 3 day hospitalization is normal for index procedure and outcome needs to be measured at discharge. | 3 days in average | 
| Each component of MACE |  | 30 days | 
| Each component of MACE |  | 9 months | 
| In-stent and in-segment restenosis rate |  | 8 months | 
| In-segment late loss |  | 8 months | 
| Percent atheroma volume of 10mm length by IVUS examination (non-target vessel) in IVUS-substudy |  | 8 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stents, angiotensin-converting enzyme