Johnson WC, Williford WO; Department of Veterans Affairs Cooperative Study #362.

[WARFARIN is COUMADIN (crystalline warfarin sodium) is an anticoagulant which acts by inhibiting vitamin K-dependent coagulation factors. Chemically, it is 3-( -acetonylbenzyl)-4-hydroxycoumarin and is a racemic mixture of the R- and S-enantiomers. Crystalline warfarin sodium is an isopropanol clathrate. The crystallization of warfarin sodium virtually eliminates trace impurities present in amorphous warfarin. Its empirical formula is C₁₉ H₁₅ NaO₄.—rxlist.com]
BACKGROUND: The benefits of the long-term administration of oral anticoagulant therapy remain unclear in patients with lower extremity arterial bypass surgery. We studied the effect of warfarin plus aspirin therapy (WASA) versus aspirin therapy alone (ASA) on patient mortality, morbidity and bypass patency [free from obstruction] rates in a randomized clinical trial. METHODS: In a multicenter, prospective, nonmasked clinical trial, 831 patients who underwent peripheral arterial bypass surgery were compared in a long-term treatment program of WASA (target international normalized ratio of 1.4 to 2.8 [serum level range] plus 325 mg/day) with [versus] ASA (325 mg/day). The primary end point was bypass patency, and mortality and morbidity were the secondary endpoints. RESULTS: There were 133 deaths in the WASA group (31.8%) and 95 deaths in the ASA group (23.0%; risk ratio, 1.41; 95% confidence interval, 1.09 to 1.84; P =.0001). Major hemorrhagic events occurred more frequently in the WASA group (WASA, n = 35; ASA, n = 15; P =.02). In the prosthetic bypass group, there was no significant difference in patency rate in the 8-mm bypass subgroup, but there was a significant difference in patency rate in the 6-mm bypass subgroup (femoral-popliteal; 71.4% in the WASA group versus 57.9% in the ASA group; P =.02). In the vein bypass group, patency rate was unaffected (75.3% in the WASA group versus 74.9% in the ASA group). CONCLUSION: The long-term administration of warfarin therapy when combined with aspirin therapy has only a few selected indications for improvement of bypass patency and is associated with an increased risk of morbidity and mortality. 

Aspirin alone prevented coronary events 27% better than either warfarin, or warfarin + aspirin

(Circulation. 2001;103:3069.)
© 2001 American Heart Association, Inc

Aspirin, Warfarin, or the Combination for Secondary Prevention of Coronary Events in Patients With Acute Coronary Syndromes and Prior Coronary Artery Bypass Surgery

Thao Huynh, MD; Pierre Théroux, MD; Peter Bogaty, MD; James Nasmith, MD; Susan Solymoss, MD

From the Montreal General Hospital (T.H., S.S.), the Montreal Heart Institute (P.T.), and Sacré-Coeur Hospital (J.N.), Montreal, Quebec, and the Quebec Heart Institute (P.B.), Quebec, Quebec, Canada.

Background—Patients with a non–ST-elevation acute coronary syndrome and prior CABG are at high risk of a recurrent ischemic event despite aspirin therapy. This trial investigated the potential benefit of secondary prevention with warfarin.

Methods and Results—In a double-blind randomized trial, 135 patients with unstable angina or non–ST-segment elevation myocardial infarction, with prior CABG, and who were poor candidates for a revascularization procedure received therapy with aspirin and placebo+warfarin, warfarin and placebo+aspirin, or aspirin and warfarin [3 groups] for 12 months. Warfarin was titrated to an international normalized ratio of 2.0 to 2.5. The primary end point (death or myocardial infarction or unstable angina requiring hospitalization 1 year after randomization) occurred in 14.6% of the patients in the warfarin-alone group, in 11.5% of patients in the aspirin-alone group, and in 11.3% of patients randomized to the combination therapy (P=0.76). Subgroup analyses by risk features provided no indications that warfarin alone or in combination with aspirin could be of benefit over aspirin alone. Bleeding was more frequent in the 2 groups of patients administered warfarin.

Conclusions—Moderate-intensity oral anticoagulation alone or combined with low-dose aspirin does not appear to be superior to low-dose aspirin in the prevention of recurrent ischemic events in patients with non–ST-elevation acute coronary syndromes and previous CABG.

^{Some troubling results:  First the aspirin was a daily does of 80 mg daily.  However after the study was completed, patients were prescribed 325 mg daily.  Secondly Warfarin was given in a high dose.  It is likely that if aspirin had been given in the commonly proscribed dose of 325 mg, its would have been even more effective—and why after the study did they raise the dose???}

In a survey of the literature, “Only aspirin in prosthetic grafts and ticlopidine in vein grafts have been shown in well designed, double-blind, randomized, controlled trials to reduce the likelihood of occlusin in infrainguinal bypass grafts.-- Review

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