The Effect of Serum LDL Lowering on Aspirin Resistance
Aspirin resistance is the persistent platelet activation, demonstrated by platelet function tests (1).
The hypothesis is that:LDL lowering by statin in patients with aspirin resistance can improve the effect of aspirin due to the potential decreasing of cholesterol content in the platelet membranes.
Patients and methods:Forty hypercholesterolemic patients with aspirin resistance after 5 days of treatment with aspirin and high LDL and triglycerides<300 mg/dL, will be enrolled.
Ten healthy volunteers will be the control group.
The patients will be treated by aspirin loading dose of 500mg and then 100 mg/day for other 4 days. For patients that will be entrolled in the regular working hours, platelet aggregation test and cholesterol content in platelet membranes will be done at baseline.
Blood tests for lipids, liver (ALT,AST,GGT,Alkaline phosphatase and bilirubin) and renal function tests (blood urea nitrogen and creatinine), complete blood count, general urine test and serum homocysteine will be done on the second day.
On the fifth day optical platelet aggregation test, cholesterol content in platelet membranes, platelet function in the PFA-100 system and soluble p-selectin in the plasma will be done If the patient has aspirin resistance (platelet aggregation20% with epinephrine or70% with ADP), LDL will be lowered in the plasma of 20 patients by hypolipidemic drugs (statin alone or combined with ezetimibe). Other 20 patients will continue to be treated by aspirin alone.
One month later, blood tests for lipids, liver (ALT,AST,GGT,Alkaline phosphatase and bilirubin) and renal function tests (blood urea nitrogen and creatinine), complete blood count, general urine test and serum homocysteine will be done for the second time and platelet activity will be tested again for all patients.
For platelet studies, venous blood (30 ml) will be collected through siliconized syringes into acid citrate dextrose solution(1.4% citric acid, 2.5% sodium citrate, and 2% dextrose) at a ratio of 9:1 (v:v) for washed platelets (WP)preparation.WP will be prepared by centrifugation at 240g for 20 min. The platelet bellet will be washed twice in 5 mmol Hepes buffer, pH 7.4 (140 mmol NaCl, 2 mmol KCL, 1 mmol MgCl2, 5 mmol Hepes, 12 mmol NaHCO3 and 5.5 mmol of glucose). For the preparation of WP suspension, 15 L of acetic acid (1mmol) will be added to 1 ml of platelet suspension throughout WP preparation in order to ensure acidic conditions which are required for platelet resuspension. This procedure will reduce the medium pH to 6.5 and it does not influence the aggregation response of the WP.
Collagen (Nycomed, germany) will be used as the aggregating agent at a concentration of 4 g/ml (this concentration can cause up to 60% aggregation amplitude in WP). Platelet aggregation will be perfomed at 37ºC in aggregometer using hepes as a reference system. Results will be expressed as the extent of maximal aggregation (% of maximal amplitude) and also as the slope of the aggregation curve (cm/min).
Cholesterol content in platelet membranes:
Platelets will be washed three times with Hepes buffer, and then sonicated twice for 20 seconds at 80 watt. Platelet lipids will be extracted with hexane:isopropanolol (3:2, v:v). The cholesterol content will be measured in the dried hexane phase by the method of Chiamori et al (12). Platelet protein will be determined using the method of Lowry (13).
Allocation: Non-Randomized, Control: Uncontrolled, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Internal Medicine Department A ,Ziv Goverment Hospital
Results (where available)
- Source: http://clinicaltrials.gov/show/NCT00466154
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
A non-steroidal anti-inflammatory agent that is less effective than equal doses of ASPIRIN in relieving pain and reducing fever. However, individuals who are hypersensitive to ASPIRIN may tolerate sodium salicylate. In general, this salicylate produces the same adverse reactions as ASPIRIN, but there is less occult gastrointestinal bleeding. (From AMA Drug Evaluations Annual, 1992, p120)
Asthmatic adverse reaction (e.g., BRONCHOCONSTRICTION) to conventional NSAIDS including aspirin use.
The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. (From Martindale, The Extra Pharmacopoeia, 30th ed, p5)
A salicylate derivative and anti-inflammatory analgesic with actions and side effects similar to those of ASPIRIN.
An anti-inflammatory analgesic and antipyretic highly bound to plasma proteins. It is pharmacologically similar to ASPIRIN, but causes less gastrointestinal bleeding.
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