Paracetamol and Endothelial Function in Patients With Stable Coronary Artery Disease

Study Overview
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Brief Summary
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The purpose of this study is to determine the effect of orally given paracetamol on the vascular function and on 24-hour blood pressure in patients with coronary artery disease

Detailed Description
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Patients with chronic pain diseases (e.g. osteoarthritis) are dependent on effective medication. NSAIDs are very effective in lowering pain in these patients. Recently there has aroused major concern with regard to cardiovascular side effects and safety, especially in selective cyclooxygenase-2 inhibitors (coxibs) but also in regular NSAIDs. At the moment, there is a big confusion, whether these drugs still should be used, especially in patients with known coronary artery disease. Physicians now try to switch to high dose paracetamol, despite the weaker efficacy in pain relieve, because this drug is considered generally as not harmful. As there is very few information on the cardiovascular effect of this drug, we plan to perform this study and investigate the impact of paracetamol on endothelial function, an important cardiovascular surrogate marker, on inflammatory markers and on oxidative stress in patients with coronary artery disease on top of standard medication, including aspirin

Official Title
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Paracetamol and Endothelial Function in Patients With Stable Coronary Artery Disease

Conditions
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Coronary Arteriosclerosis, Endothelial Function

Intervention / Treatment
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* Drug: Paracetamol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 30 - 80 years History of coronary artery disease (documented by coronary angiogram, nuclear imaging, positive stress test) Stable cardiovascular medication for at least 1 month Written obtained informed consent Exclusion Criteria:- myocardial infarction, unstable angina, stroke within 3 months prior to study entry coronary intervention/revascularisation procedure within 3 months prior to study entry Left ventricular ejection fraction <50% Other analgesics (Platelet inhibition therapy with Aspirin 100mg/d will be continued) Long acting nitrates Smoking Chronic heart failure (> NYHA II) Ventricular tachyarrhythmias Renal failure (serum creatinine >200umol) Liver disease (ALT or AST >100 IU), especially acute hepatitis Hyperbilirubinemia Alcohol abuse Oral Anticoagulation Concomitant therapy with Phenobarbital, Phenytoin, Carbamazepin, Isonicotinic Acid, Chloramphenicol Chlorzoxazone, Zidovudine, Salicylamide Insulin-dependent diabetes mellitus Drug abuse Anemia (Hb<10 g/dl) Known allergies on Paracetamol Pregnancy Malignancy (unless healed or remission > 5 years) Symptomatic hypotension, hypertension >160/100 mmHg Disease with systemic inflammation (e.g. rheumatoid arthritis, M. Crohn) Participation in another study within the last month

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 80 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: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Paracetamol|Paracetamol 3x1000mg daily or Placebo for two weeks in a crossover design with a two-week washout-phase in between.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Efficacy endpoint: To investigate the effect of paracetamol on endothelial function as compared to placebo in patients with stable coronary artery disease. |  | 2 weeks | 
| primary safety endpoint: to evaluate the effect of paracetamol on 24-hour systolic and diastolic blood pressure as compared to placebo in patients with stable coronary artery disease. |  | 2 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To investigate the effect of paracetamol on markers of inflammation and oxidative stress as well as platelet function |  | two weeks |