A Prospective Study to Evaluate the Effect of Chronic Nitrate Therapy on Vasodilation Function in Coronary Heart Disease

• Conditions: Coronary Artery Disease
• Interventions: Drug: control group; Drug: nitrate group

• Registration Number: NCT01430780
• Lead Sponsor: Zhejiang University

Brief Summary

Basic studies has showed that sustained use of nitrates might associated with adverse effects on vascular function mediated by an increase in nitrate-induced oxidative stress. But it remains unclear whether oxidative stress increases with endothelial function impairment in patients with coronary artery disease (CAD) during administration of long-term oral nitrates. The investigators evaluated whether administration of long-term isosorbide mononitrate (ISMN) treatment was associated with oxidative stress increase and endothelial function impairment in patients with CAD.

Detailed Description

Organic nitrates are widely prescribed for the treatment of angina pectoris in patients with coronary artery disease (CAD). In China, many patients with CAD are prescribed nitrates as a long-term treatment. The most commonly prescribed nitrates for long-time treatment is isosorbide mononitrate (ISMN). The reason for their use is that the majority of physicians believe chronic therapy with organic nitrates is associated with an improvement in symptoms and has neutral or potentially beneficial effects on long-term patient outcome, although this assumption remains unproven.

Recently, multiple lines of evidence documented that sustained use of nitrates was associated with adverse effects on vascular function which appeared to be mediated by an increase in nitrate-induced oxidative stress. The accumulation of oxygen free radicals during chronic nitrate therapy was associated with endothelial dysfunction, increased arterial sensitivity to vasoconstrictors and the development of abnormalities in a number of important enzymes involved in the regulation of vascular homeostasis, including the superoxide dismutase, protein kinase C, matrix metalloproteinases, and prostaglandin synthase. This may lead to development of nitrate tolerance, endothelial dysfunction. Furthermore, endothelial dysfunction is a risk factor for worse prognosis of patients with CAD.

Up to date, some clinical research focus on how to prevent tolerance and clinical outcome of nitrate therapy were involved short follow-up periods of only a few weeks. It is too short to assess the true clinical impact of nitrate-induced endothelial dysfunction, and the safety of long-term nitrate therapy requires systematic review. So prospective, randomized study with longer treatment period is needed to observe the chronic impact of nitrate therapy on endothelial function.

Therefore, the investigators prospectively investigated whether long-term ISMN therapy had any influence on endothelial function evaluated by brachial artery ultrasound imaging during reactive hyperemia in patients with catheterization confirmed CAD, and whether this was associated with increased oxidization or inflammation burden.

Study Timeline

• Study Start: 2009-08
• Study First Submitted: 2011-09-01
• Study First Submitted QC: 2011-09-06
• Study First Posted: 2011-09-08
• Status Verified: 2013-03
• Last Update Submitted: 2013-03-21
• Last Update Posted: 2013-03-22
• Primary Completion: 2013-12
• Study Completion: 2013-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 68

Inclusion Criteria

• Individuals were considered eligible for enrollment if they had at least 1 significant de novo stenosis (reduction ≥50% of the lumen diameter) on any coronary vessel at angiography.

Exclusion Criteria

• Patients with liver and renal failure with creatinine>3 mg/dL were excluded.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
control group	control group	placebo
nitrate group	nitrate group	Isosorbide Mononitrate orally 20mg twice per day.

Primary Outcome Measures

Name	Time	Method
flow-mediated dilation	one year	Endothelial function evaluated by brachial artery ultrasound imaging during reactive hyperemia.

Secondary Outcome Measures

Name	Time	Method
serum superoxide dismutase (SOD) level	one year	Superoxide dismutase (SOD) was determined by Xanthinoxidase method.
serum malondialdehyde (MDA) level	one year	Malondialdehyde (MDA) was determined by thiobarbituric acid method.
serum hypersensitive C-reactive protein (hsCRP) level	one year	An ELISA was used to determine hypersensitive C-reactive protein (hsCRP).

Trial Locations

Locations (1)

Department of Cardiology, First Affiliated Hospital, College of Medicine, Zhejiang University; 🇨🇳 Hangzhou, Zhejiang, China