Aspirin Dose and Atherosclerosis in Patients With Metabolic Syndrome

Cardiovascular Diseases Clinical Trial

— PAD  

Official title:

A Randomized, Double-Blind Trial to Test Higher- Versus Lower-Doses of Aspirin on Inflammatory Markers and Platelet Biomarkers and Nitric Oxide Formation in High Risk Primary Prevention (Patients With Metabolic Syndrome)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00272311
• Other study ID #: H08-35
• Status: Completed
• Phase: Phase 4
• Start date: October 2006
• Est. completion date: January 2009

Study information

• Verified date: February 2019
• Source: Florida Atlantic University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to test higher versus lower doses of aspirin on markers of atherosclerosis in patients at risk of a first heart attack.

Description:

Aspirin reduces risks of heart attacks, strokes, and deaths from cardiovascular causes in patients who have survived a prior event as well as during an acute heart attack. Aspirin also prevents a first heart attack.

Low dose aspirin is sufficient to achieve complete inhibition of platelet aggregability, or stickiness, and this is the mechanism whereby aspirin prevents formation of blood clots.

Our research is designed to explore whether higher doses of aspirin provide additional benefits on markers of atherosclerosis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: January 2009
• Est. primary completion date: January 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

Inclusion Criteria:

• 1. Age 40 to 80 years, inclusive.

2. No previous heart attack or a stroke, or other forms of these diseases.

3. Have at least three of the five characteristics listed below, indicating presence of metabolic syndrome, as defined by NCEP-III:

1. waist measuring more than 40 inches (for men) or more than 35 inches (for women),

2. high density lipoprotein (HDL) cholesterol levels lower than 40 milligrams per deciliter (mg/dl) in men or 50 mg/dl in women,

3. triglyceride (TG) levels above 150 mg/dl,

4. blood pressure greater than 130 millimeters of mercury (mmHg) systolic or 85 mmHg diastolic,

5. fasting blood sugar greater than 110 mg/dl

Exclusion Criteria:

1. Patients taking greater than 81mg aspirin daily.

2. Patients taking anti-platelet drugs such as clopidogrel or non-steroidal anti-inflammatory drugs (NSAIDs) or anticoagulant drugs such as warfarin, during the last two weeks.

3. Patients taking any of the following medications for less than 3 months, or who plan to take them for the first time during the next 3 months: ACE-inhibitors, angiotensin receptor blockers, calcium channel blockers, or statins.

4. Patients who are currently cigarette smokers.

5. Women patients who are pregnant, planning to become pregnant, nursing a child, or taking hormone replacement therapy.

6. Patients with any coagulation, bleeding or blood disorders.

7. Patients who are sensitive or allergic to aspirin.

8. Patients with documented history of any gastrointestinal disorders, including bleeding ulcers.

9. Patients with any evidence of cancer or history of significant cardiovascular disease (including heart attack, stroke or drop attacks termed transient ischemic attacks (TIAs), or blockages of the arteries in the legs termed peripheral arterial disease (PAD)), kidney, liver, lung, blood, or brain disorders.

10. Patients with asthma, rhinitis, or nasal polyps.

11. Patients with any abnormal laboratory value or physical finding that, in the view of the responsible clinician, may interfere with interpretation of the study results, be indicative of an underlying disease state, or compromise the safety.

12. Patients with Class IV heart failure.

13. Patients with severe aortic insufficiency, or aortic regurgitation.

14. Patients with hearing loss or tinnitus.

15. Patients with tremors which cause them not to be able to remain motionless for approximately 30 seconds.

Related Conditions & MeSH terms

• Atherosclerosis
• Cardiovascular Diseases
• Metabolic Syndrome
• Metabolic Syndrome X
• Syndrome

Intervention

Drug:
• Aspirin
Dosage

Locations

Country	Name	City	State
United States	HeartDrug Research, LLC	Towson	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Florida Atlantic University	Bayer

Country where clinical trial is conducted

United States, 

References & Publications (20)

Eidelman RS, Hebert PR, Weisman SM, Hennekens CH. An update on aspirin in the primary prevention of cardiovascular disease. Arch Intern Med. 2003 Sep 22;163(17):2006-10. — View Citation

Grosser N, Abate A, Oberle S, Vreman HJ, Dennery PA, Becker JC, Pohle T, Seidman DS, Schröder H. Heme oxygenase-1 induction may explain the antioxidant profile of aspirin. Biochem Biophys Res Commun. 2003 Sep 5;308(4):956-60. — View Citation

Hennekens CH, Buring JE, Sandercock P, Collins R, Peto R. Aspirin and other antiplatelet agents in the secondary and primary prevention of cardiovascular disease. Circulation. 1989 Oct;80(4):749-56. Review. — View Citation

Hennekens CH, Dyken ML, Fuster V. Aspirin as a therapeutic agent in cardiovascular disease: a statement for healthcare professionals from the American Heart Association. Circulation. 1997 Oct 21;96(8):2751-3. — View Citation

Hennekens CH, Hollar D, Baigent C. Sex-related differences in response to aspirin in cardiovascular disease: an untested hypothesis. Nat Clin Pract Cardiovasc Med. 2006 Jan;3(1):4-5. — View Citation

Hennekens CH, Schror K, Weisman S, FitzGerald GA. Terms and conditions: semantic complexity and aspirin resistance. Circulation. 2004 Sep 21;110(12):1706-8. Review. — View Citation

Ikonomidis I, Andreotti F, Economou E, Stefanadis C, Toutouzas P, Nihoyannopoulos P. Increased proinflammatory cytokines in patients with chronic stable angina and their reduction by aspirin. Circulation. 1999 Aug 24;100(8):793-8. — View Citation

Mustard JF, Moore S, Packham MA, Kinlough-Rathbone RL. Platelets, thrombosis and atherosclerosis. Prog Biochem Pharmacol. 1977;13:312-25. — View Citation

Mustard JF, Packham MA, Kinlough-Rathbone RL. Platelets and thrombosis in the development of atherosclerosis and its complications. Adv Exp Med Biol. 1978;102:7-30. Review. — View Citation

Mustard JF, Packham MA. The role of blood and platelets in atherosclerosis and the complications of atherosclerosis. Thromb Diath Haemorrh. 1975 Jun 30;33(3):444-56. — View Citation

Oberle S, Polte T, Abate A, Podhaisky HP, Schröder H. Aspirin increases ferritin synthesis in endothelial cells: a novel antioxidant pathway. Circ Res. 1998 May 18;82(9):1016-20. — View Citation

Patrignani P, Filabozzi P, Patrono C. Selective cumulative inhibition of platelet thromboxane production by low-dose aspirin in healthy subjects. J Clin Invest. 1982 Jun;69(6):1366-72. — View Citation

Pearson TA, Blair SN, Daniels SR, Eckel RH, Fair JM, Fortmann SP, Franklin BA, Goldstein LB, Greenland P, Grundy SM, Hong Y, Miller NH, Lauer RM, Ockene IS, Sacco RL, Sallis JF Jr, Smith SC Jr, Stone NJ, Taubert KA. AHA Guidelines for Primary Prevention of Cardiovascular Disease and Stroke: 2002 Update: Consensus Panel Guide to Comprehensive Risk Reduction for Adult Patients Without Coronary or Other Atherosclerotic Vascular Diseases. American Heart Association Science Advisory and Coordinating Committee. Circulation. 2002 Jul 16;106(3):388-91. Review. — View Citation

Reilly IA, FitzGerald GA. Inhibition of thromboxane formation in vivo and ex vivo: implications for therapy with platelet inhibitory drugs. Blood. 1987 Jan;69(1):180-6. — View Citation

Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med. 1997 Apr 3;336(14):973-9. Erratum in: N Engl J Med 1997 Jul 31;337(5):356. — View Citation

Roth GJ, Stanford N, Majerus PW. Acetylation of prostaglandin synthase by aspirin. Proc Natl Acad Sci U S A. 1975 Aug;72(8):3073-6. — View Citation

Steer KA, Wallace TM, Bolton CH, Hartog M. Aspirin protects low density lipoprotein from oxidative modification. Heart. 1997 Apr;77(4):333-7. — View Citation

U.S. Preventive Services Task Force. Aspirin for the primary prevention of cardiovascular events: recommendation and rationale. Ann Intern Med. 2002 Jan 15;136(2):157-60. — View Citation

Williams A, Hennekens CH. The role of aspirin in cardiovascular diseases--forgotten benefits? Expert Opin Pharmacother. 2004 Jan;5(1):109-15. Review. — View Citation

Wu R, Lamontagne D, de Champlain J. Antioxidative properties of acetylsalicylic Acid on vascular tissues from normotensive and spontaneously hypertensive rats. Circulation. 2002 Jan 22;105(3):387-92. — View Citation

* Note: There are 20 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in Inflammatory Markers From Baseline to 3 Months.		Baseline to 3 Months (90-97 days)
Other	Change in Platelet Biomarkers From Baseline to 3 Months.		Baseline to 3 Months (90-97 days)
Primary	Change in Nitric Oxide Formation From Baseline to 3 Months	Changes in Heme oxygenase (HO-1) a downstream target of nitric oxide (NO) formation.	Baseline to 3 Months (90-97 days)