ASA MOA

• When platelets come in contact with the endothelium, they become activated one of the chemical messengers released by platelets is thromboxane A2 or TXA2. 
• ASA binds irreversibly to COX (cyclooxygenase) which stops the production of TXA2 in platelets.
• The inactivation of cox is irreversible. Therefore asa blocks the function of affected platelets for the life of the platelet or 7-10 days.

AFASAK (1989)

SPAF1 (1991)

EAFT (1993)

Key points of AFASAK

• Primary Outcome = stroke, systemic embolism, tia
• 5.2% asa vs 6.2% placebo
• RR=16% p=ns

• patients randomized to asa 325 daily (n 552) vs. placebo (n 568)
• primary endpoint: ischemic stroke or systemic embolism
• event rate 3.6% vs 6.3%
• 42% RR reduction p=.02

• meta analysis of data from 8 trials showed that warfarin reduced the risk of stroke by 38% compared to asa
• the absolute risk reduction was 0.7% for primary prevention and 7.0% for secondary prevention.
• trials were: afasak, spaf ii, eaft, afasakii, pataf and chinese atafs.

Guideline recommendation for asa?

• ACCP: CHADS = 0 - ASA 75-325MG/DAY. CHADS = 1 -- ASA 75 TO 325 OR WARF INR 2.5 RANGE 2.0-3.0 CHADS ≥2 ---- WARF TRGT INR 2.5 RANGE 2.0-3.0
• ACC/AHA/ESC SAME EXCEPT LOW DOSE ASA 81 MG.

• BLEEDING AND GI TOXICITY.
• BOTH DUE TO COX INHIBITION
• BLEEDING DUE TO INHIBITION OF PLATELETS
• GI DUE TO COX INHIBITION IN THE GI MUCOSA WHICH RESULTS IN DECREASED PRODUCTION OF PROSTAGLANDINS, WHICH DECREASES THE PROTECTIVE EFFECTS OF PROSTAGLANDINS ON THE GI MUCOSA
• GI EFFECTS APPEAR TO BE DOSE RELATED AND AGE RELATED. ALTHOUGH ASA CAN CAUSE SERIOUS BLEEDING AT DOSES AS LOW AS 30MG... ABOVE AGE 70 6 FOLD INCREASE IN RISK OF GASTRIC COMPLICATIONS.

• abdominal pain 
• nausea
• gastric ulcers
• dyspepsia
• gastric erosions
• gi hemorrhage
• perforation