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

Phase 4

Completed

• Conditions: Coronary Artery Disease
• Interventions: Drug: Valsartan

• Registration Number: NCT00589732
• Lead Sponsor: Seung-Jung Park

Brief Summary

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

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.

Study Timeline

• Study Start: 2006-09
• Study First Submitted: 2007-12-31
• Study First Submitted QC: 2007-12-31
• Study First Posted: 2008-01-10
• Primary Completion: 2009-12
• Study Completion: 2009-12
• Status Verified: 2012-08
• Last Update Submitted: 2012-08-07
• Last Update Posted: 2012-08-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 220

Inclusion Criteria

1. 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
2. Angiographic: Patients who have

1. Significant ischemic narrowing (target vessel)

1. De novo coronary lesion (no restriction of lesion length)
2. Percent diameter stenosis ≥50% by visual estimate
3. Reference vessel size ≥2.5 mm by visual estimation
4. Lesions suitable for stenting

And/Or

2. Non-significant non-ischemic intermediate narrowing (non-target vessel)

1. Percent diameter stenosis 20%~50% by visual estimate
2. No objective evidence of ischemia

Exclusion Criteria

1. Patients received a Angiotensin converting enzyme inhibitor (ACE-I) or ACE-receptor blockers (ARBs) in the previous week prior to enrollment
2. History of bleeding diathesis or coagulopathy
3. Pregnant
4. Known hypersensitivity or contra-indication to contrast agent and heparin
5. Limited life-expectancy (less than 1 year)
6. Acute ST-elevation myocardial within 1 week
7. Characteristics of lesion 1) Left main disease 2) In-stent restenosis 3) Graft vessels
8. Hematological disease (Neutropenia <3000/mm3, Thrombocytopenia <100,000/mm3)
9. Hepatic dysfunction, liver enzyme (ALT and AST) elevation >3 times normal
10. Renal dysfunction, creatinine >2.0mg/dL
11. Contraindication to aspirin and clopidogrel

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Valsartan treatment gorup	Valsartan	Valsartan 160mg per day group

Primary Outcome Measures

Name	Time	Method
Angiographic in-stent late-loss (target vessel)	at 8-month follow-up.

Secondary Outcome Measures

Name	Time	Method
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	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

Trial Locations

Locations (5)

St. Mary's Catholic Medical Center; 🇰🇷 Seoul, Korea, Republic of

Asan Medical Center; 🇰🇷 Seoul, Korea, Republic of

Samsung Medical Center; 🇰🇷 Seoul, Korea, Republic of

Yonsei University Medical Center; 🇰🇷 Seoul, Korea, Republic of

Ajou University Hospital; 🇰🇷 Suwon, Korea, Republic of