TIGC Guidelines
Primary Category: Antiplatelet Therapy
Guide Title: Antiplatelet Therapy
Date Revised: November 16, 2008
Principal Developer: J. Lam
Secondary Developer: A. Bell, A. Roussin
Background
Antiplatelet agents are drugs which interfere with the ability of platelets to aggregate and form a platelet plug. As antithrombotic agents, they are most useful in clinical states due to arterial vascular disease.
Available Agents
The cheapest and most widely used agent is ASA. Ticlopidine and clopidogrel are newer, and are recommended for patients with ASA allergy or intolerance, and when clinical events arise despite ASA therapy. Clopidogrel is recommended over ticlopidine because it is associated with less serious side effects and provides superior benefit to ASA in patients with vascular disease, such as stroke, myocardial infarction or peripheral arterial disease. This benefit of clopidogrel is enhanced in patients at higher risk, such as those with hyperlipidemia, diabetes, prior coronary bypass surgery and disease in multiple vascular beds. ASA and clopidogrel have a synergistic effect and is recommended after an episode of non-ST-segment elevation (NTSE) acute coronary syndromes (ACS) and in patients undergoing coronary stenting, where the combination has been shown to provide better cardiovascular protection. The use of sulfinpyrazone as antithrombotic agents either alone or in combination with other antiplatelet agents is not recommended. There is no evidence for dipyridamole alone or in addition to, ASA and clopidogrel in the management of patients with ACS. ASA, clopidogrel or extended-release dipyridamole in combination with ASA are acceptable options for prevention of ischemic stroke. Results of ongoing clinical studies will clarify the role of the ASA-dipyridamole combination versus other anti-platelet strategies in stroke prevention.
Indications
An overview of randomized clinical trials have shown that the risk of major vascular events (myocardial infarction, stroke and vascular death) is reduced by approximately 25% and the risk of mortality is reduced by approximately 15% in patients with atherosclerotic vascular disease at high risk.
Cardiac
In patients with ACS with and without ST-segment elevation, regular uncoated ASA should be given as soon as the diagnosis is made, whether or not thrombolytic therapy and/or heparin is to be administered. ASA is also recommended for patients with stable angina, post-angioplasty and CABG where it helps maintain patency as well as reduce the incidence of serious vascular events. ASA should be continued indefinitely in all patients unless there are indications for use of warfarin. (See Antithrombotic Therapy Post-MI guidelines). Among high-risk NSTE ACS patients, recent evidence suggest added benefit from combination antiplatelet regimen. Clopidogrel (or ticlopidine in case of clopidogrel intolerance) is an effective alternative in cases of ASA intolerance or allergy. Clopidogrel, 300mg loading, followed by 75mg daily in addition to ASA is recommended for at least 9 to 12 months in all patients presenting with NSTE ACS. This combination may also be useful in stable coronary patients at high risk. In moderate to high risk-patients presenting with NSTE ACS, there is additional benefit from the early initiation of GP llb/llla inhibitors such as eptifibatide or tirofiban in addition to ASA and heparin.
Indications:

1. Antiplatelet therapy is STRONGLY RECOMMENDED for ALL patients with the following unless contraindicated:
A. Cardiac
·         ACS patients with and without ST-segment elevation
·         Chronic stable angina or documented coronary disease 
·         following angioplasty or CABG
B. Cerebrovascular
·         post TIA, completed strokes 
·         following carotid endarerectomy
C. Peripheral Vascular Disease
·         any peripheral vascular disease
2. Antiplatelet therapy MAY BE BENEFICIAL in the following:
A. Cardiac
·         atrial fibrillation if warfarin contraindicated. 
·         mechanical heart valve in combination with warfarin. 
·         patients over 50 yrs old with at least 1 additional cardiac risk factor for atherosclerosis.
B. Cerebrovascular
·         carotid artery disease
C. Peripheral Vascular Disease
The use of ASA may modify the natural history of intermittent claudication due to peripheral vascular disease. In the absence of contraindications, ASA is recommended for patients with peripheral vascular disease for reduction of cardiovascular events (myocardial infarction and stroke). Clopidogrel may be superior to ASA in reducing ischemic complications in patients with peripheral vascular disease.
Primary Prevention
Although ASA has been shown to be effective in primary prevention of vascular disease, the overall benefit is small. Therefore, it is prudent to limit its use to individuals 50 years old with one additional risk factor for coronary disease (i.e. diabetes, hypertension, smoking, hyperlipidemia, sedentary lifestyle).
Dosage and Administration
The usual antiplatelet dose of ASA is 75-325 mg daily. An initial dose of 160 to 325 mg is recommended, and then indefinite therapy with 75 to 162 mg/d. For those with a history of ASA-induced bleeding or at risk for bleeding, chronic lower dose of ASAis recommended, <100mg/d. In individuals with cerebrovascular disease, there may be additional benefits to ASA given in association with slow release dipyridamole, 200 mg BID, although although this combination has not been shown to decrease coronary events. When used in combination with clopidogrel, the dose of ASA should be <100 mg/d.
 ASAintolerance or allergy, and/or patients who have recurrent events despite ASA therapy. Clopidogrel, 300 mg oral bolus, followed by75 mg daily, is an effective alternative to ticlopidine, and is preferred over ticlopidine because it is associated with fewer serious side effects and does not require frequent monitoring of blood counts.
 
Side Effects
The most common side effect of ASA is gastrointestinal intolerance which is dose related. Bleeding is a potential complication.
 
The most common side effect of Clopidogrel is skin rash. Neutropenia is uncommon, as infrequent as with ASA, and monitoring of the WBC is not necessary.
Contraindications
  • familial or acquired bleeding disorder
  • thrombocytopenia
  • allergy to proposed drug
  • caution should be exercised when administering ASA to patients with asthma and other allergic disorders
  • active bleeding
References
  1. Hirsh et al. Chest 1998; 114 (Suppl):439-769S.
  2. Seventh ACCP Consensus Conference on Antithrombotic Therapy. http://www.chestjournal.org/content/vol126/1_suppl/
  3. Antiplatelet Trialists' Collaboration. BMJ 1994; 308:81, 159 and 235.
  4. CAPRIE Steering Committee. Lancet 1996; 348:1329.
  5. CURE study investigators. N Engl J Med 2001; 345:494-502
  6. ACC/AHA/ACP-ASIM Guidelines for the management of patients with chronic stable angina. J Am Coll Cardiol. 1999; 33:2092
  7. ACC/AHA Guidelines for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction. Circulation 2002; 106:1893.
  8. Boersma et al. Lancet 2002; 359:189-198
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