Chronic stable angina treatment clopidogrel

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [mailto:mgibson@perfuse.org] Phone:617-632-7753; Associate Editor(s)-In-Chief: ; John Fani Srour, M.D.; Jinhui Wu, M.D.; Lakshmi Gopalakrishnan, M.B.B.S.

Overview
Thienopyridines, such as clopidogrel and ticlopidine, selectively inhibit ADP-induced platelet aggregation and are used as an alternative to aspirin in patients with significant risk of arterial thrombosis.

Mechanisms of benefit

 * Clopidogrel is a thienopyridine derivative which prevents adenosine diphosphate–mediated activation of platelets by selectively and irreversibly inhibiting the binding of adenosine diphosphate to its platelet receptors and thereby, blocking adenosine diphosphate–dependent activation of the glycoprotein IIb/IIIa complex.


 * Ticlopidine, another thienopyridine derivative, decreases platelet function in patients with stable angina but, unlike aspirin, has not been shown to decrease adverse cardiovascular events.

Indication
Clopidogrel is used in patients with contraindication to aspirin or aspirin intolerance.

Drug interactions

 * Use of warfarin in conjunction with aspirin and/or clopidogrel is associated with an increased risk of bleeding and therefore, close monitoring is required.


 * Atorvastatin via ADP mediated platelet activation inhibits clopidogrel. However, this inhibition is not observed with low dose atorvastatin (10mg).
 * Clopidogrel is metabolized via CYP-3A4, hence drugs that inhibit (erythromycin) or induce (rifampicin) CYP-34A alter the plasma levels of clopidogrel.

Adverse effects

 * Clopidogrel:
 * Gastrointestinal bleed
 * Active bleeding


 * Ticlopidine:
 * Neutropenia
 * Thrombocytopenia

Supportive trial data

 * The CAPRIE trial, a randomized blinded study of 19,185 patients with atherosclerotic vascular disease assessing the efficacy of clopidogrel versus aspirin therapies, showed a modest difference in the effectiveness between clopidogrel and aspirin. There was a relative risks reduction of 8.7% in favor of clopidogrel therapy among patients with established atherosclerotic vascular disease in reducing the combined risk of ischemic stroke, myocardial infarction and vascular death.


 * The CURE trial, a randomized placebo controlled studying involving 12,562 who received either clopidogrel or placebo in addition to aspirin for 3-12 months after the first 24 hours of onset of symptoms, demonstrated the efficacy and safety of adding clopidogrel (a loading dose of 300 mg, followed by 75 mg daily) to aspirin in the long-term management of patients with acute coronary syndromes without ST-segment elevation.


 * The CHARISMA trial, a randomized placebo controlled study involving 2,163 patients, reported dual anti platelet therapy with clopidogrel plus aspirin was not significantly effective in comparison to aspirin alone in reducing the rate of myocardial infarction, stroke, or cardiovascular death in patients with established vascular disease or at high risk for developing vascular disease.

==ACC/AHA Guidelines- Pharmacotherapy to Prevent MI and Death and Reduce Symptoms (DO NOT EDIT)  == {{cquote|

Class I
1. Use of warfarin in conjunction with aspirin and/or clopidogrel is associated with an increased risk of bleeding and should be monitored closely. (Level of Evidence: B)

Class IIa
1. Clopidogrel when aspirin is absolutely contraindicated. (Level of Evidence: B)}}

==ESC Guidelines- Pharmacological therapy to improve prognosis in patients with stable angina (DO NOT EDIT) == {{cquote|

Class IIa
1. Clopidogrel as an alternative antiplatelet agent in patients with stable angina who cannot take aspirin (e.g. aspirin allergic). (Level of Evidence: A)}}

Vote on and Suggest Revisions to the Current Guidelines

 * The Chronic Stable Angina Living Guidelines: Vote on current recommendations and suggest revisions to the guidelines

Guidelines Resources

 * The ACC/AHA/ACP–ASIM Guidelines for the Management of Patients With Chronic Stable Angina


 * The ACC/AHA 2002 Guideline Update for the Management of Patients With Chronic Stable Angina


 * Guidelines on the management of stable angina pectoris: The Task Force on the Management of Stable Angina Pectoris of the European Society of Cardiology


 * The 2007 Chronic Angina Focused Update of the ACC/AHA 2002 Guidelines for the Management of Patients With Chronic Stable Angina