Warfarin and aspirin combination in acute coronary syndrome: "benefits far outweigh the risks for many patients". But, it cannot be recommended in most settings because of inadequate INR management?

Henry I. Bussey, Pharm.D., FCCP, FAHA
August, 2005

The authors of a meta analysis in the August 6, 2005 issue of Annals of Internal Medicine examined the combined use of warfarin and aspirin vs. aspirin alone in acute coronary syndrome patients who did not undergo coronary stenting. ¹ The authors identified 10 trials that included more than 11, 000 patient-years of data. Their findings indicated approximately 45% to 55% relative risk reduction in stroke and recurrent myocardial infarction with the addition of warfarin. They further calculated that adding warfarin to aspirin for patients at high cardiovascular risk but low bleeding risk could avert 83 myocardial infarctions and 43 strokes per 1,000 patient-years of therapy at the expense of 6 major bleeding episodes. The number needed to treat for 3 months to prevent one major cardiovascular event was only 16 while the number needed to harm for the same period was 333. The relative risk reduction appeared to be the same across various risk categories. Furthermore, even though the greatest benefit was seen during the first 3 months after the event, the benefit did persist for up to 5 years.

Although it was not the focus of this meta analysis, it should be acknowledged that two of the landmark studies in the report (the WARIS II and ASPECT 2) also contained a third group which received warfarin alone at an INR of approximately 3 to 4.^2,3 In both studies, the warfarin only group received at least as much benefit without an increase in bleeding rates over the warfarin (INR approximately 2 to 3) plus aspirin group. Consequently, it would appear that either warfarin (INR 2 to 3) plus aspirin or warfarin alone (INR approximately 3 to 4) is superior to aspirin alone in ACS patients who do not undergo stinting; and warfarin alone may even be better in some respects.

If the "benefits far outweigh the risks for many patients", why is warfarin not used more often following ACS? Actually, the current recommendations from the American College of Chest Physicians (ACCP) for low or moderate risk patients do "recommend the combination of warfarin (INR 2 to 3) plus aspirin or warfarin alone (INR 3 to 4) for up to 4 years after an event "in health-care settings in which meticulous INR monitoring is standard and routinely accessible".⁴ However, for "most health-care settings" they recommend aspirin alone over oral anticoagulation plus aspirin. It seems a shame that ACCP felt that therapy in which "benefits far outweigh the risks for many patients" has to be restricted to only a minority of settings in which good INR monitoring is routinely available. With today's technology, one would think that such management should be available almost anywhere so that such beneficial therapy could be made widely available to these patients.

References

1. Rothberg MB, Celestin C, Fiore LD, Lawler E, Cook JR. Warfarin plus aspirin after myocardial infarction or the acute coronary syndrome: Meta-analysis with estimates of risk and benefit. Annals Internal Medicine. 2005; 143:241-250.
   
   
2. Hurlen M, Abdelnoor M, Smith P, Erikssen J, Arnesen H. Warfarin, aspirin, or both after myocardial infarction. New England Journal of Medicine. 2002; 347:969-975.
   
   
3. van Es RF, Jonker JJ, Verheugt FW, Deckers JW, Grobbee DE. Aspirin and coumadin after acute coronary syndromes (the ASPECT-2 study): a randomised controlled trial. Lancet. 2002; 360:109-113.
   
   
4. Harrington RA, Becker RC, Ezekowitz M, Meade TW, O'Connor CM, Vorchheimer DA, Guyatt GH. Atithrombotic therapy for coronary artery disease. The seventh ACCP conference on antithrombotic and thrombolytic therapy. Chest. 2004; 126:513s-548s.