aspirin plus warfarin for afib and cad???

a remarkably​ common clinical situation is the patient with coronary artery disease (CAD) who develops atrial fibrillation. do you keep the aspirin (ASA) or other antiplatelet therapy (APT) when starting oral anticoagulants (OAC) such as warfarin??? in theory, these are 2 very different drugs targeting 2 different ongoing mechanisms: aspirin and other APTs inhibit platelets and arterial clots, acute coronary syndromes (ACS), etc; warfarin and other OACs inhibits blood coagulation which interferes with venous clots and venous thrombosis, pulmonary embolism, etc. but there is clearly a higher risk of bleeding if the combo of OAC and APT are used. The ORBIT-AF registry trial (see aspirin and warfarin in afib cad ORBIT HF circ 2012 in dropbox, or doi: 10.1161/CIRCULATIONAHA.113.002927), looked at 10126 patients from 176 US practices, found that the combination of ASA and OAC was common (35% of patients), that 39% had no history of documented atherosclerotic disease, and that there was an associated 53% increased risk of major bleeding and 52% increased risk of hospitalization for major bleeding, and (though the numbers were low) rates of ischemic events in the combo group vs the OAC group were the same:  0.48% (11 patients) in the combo group vs 0.38% in the OAC only group (16 patients) after 6 months followup. 

the CORONOR study, a prospective French observational study with a really good name, looked at the same issue (see afib and cad aspirin JACC 2014 in dropbox, or doi.org/10.1016/j.jacc.2014.07.957)​. 4184 consecutive CAD patients who had not had a recent MI or coronary revascularization (for at least one year) were followed for 2 years, also finding increased bleeding with the combo therapy and no difference in cardiac outcomes. details:

--baseline characteristics: median 67 years old, 78% men, 62% prior MI, 99% prior cath, 58% multi-vessel disease, 86% prior revascularization procedure, and almost all on statin, b-blocker, ACE/ARB, and 77% on ASA, 40% clopidogrel, 21% both, and 11% on OAC mostly for atrial fib (65% of whom had combo OAC and antiplatelet drug, with n=342).
--patients who had major bleeding events on multivariate analysis, not surprisingly, were on OAC (HR of 4.69), had diabetes (HR of 2.76), were older (HR of 1.04 per year), and had impaired renal function (HR of 0.98 for each ml/min/1.73 m² decrease in eGFR).
--risk of bleeding: when compared to antiplatelet monotherapy, the risk for bleeding from OAC alone was nonsignificantly higher (HR, 1.69)​, but was was much higher when OAC was combined with APT(HR, 7.30)
--major bleeding sites: GI (55%), intracranial (20%). of the 51 patients with major bleeds (0.6%/yr), 18 events were fatal (35.3%)
--there was no difference in the combined endpoints of cardiovascular death, MI, or nonhemorrhagic stroke in those on combo therapy vs those on OAC alone (HR 1.15, with CI 0.58-2.27 and p=0.697). their figure 3 shows that the incidence of these endpoints was pretty similar in the 2 groups over a period of 800 days.

a few comments:
--from several studies, aspirin by itself doesn't work so well for atrial fibrillation. 
--BUT, OACs seem pretty good for those with acute coronary syndromes or recent MIs. the WARIS II study of 3620 patients post-MI found that after 4 years the endpoint of death, nonfatal reinfarction or thromboembolic stroke was lower in those on warfarin than on aspirin alone for secondary prevention after MI.  The SPORTIF III and IV trials with patients with atrial fibrillation randomized to warfarin (INR target 2-3) vs ximelagatran, with low-dose aspirin allowed. secondary analysis of the 14% of patients on aspirin (69% with CAD, 26% with previous stroke of TIA, 41% with LV dysfunction), found no difference in the combo therapy in terms of stroke or systemic embolism. and the rate of MI in the combo group (0.6%/yr) was not significantly different from warfarin alone (1.0%/yr), but the combo group had more major bleeding (3.9%/yr vs 2.3%/yr).
--the European Society of Cardiology's 2010 guidelines on atrial fibrillation suggest OAC monotherapy in those with atrial fibrillation and stable vascular disease (ie, >1 year with no acute events) and that antiplatelet therapy "should not be prescribed" in those without a subsequent cardiovascular event. the American College of Chest Physicians clinical practice guidelines -- see dvt guidelines Chest 2012​ in dropbox, or Chest. 2012 Feb; 141 (2 Suppl):e531S-75S) -- similarly recommends that for those with atrial fib and high CHADS(2) score who do not have an intracoronary stent placed and are on OAC plus APT therapy for one year, to stop the APT.​

so, as per usual, would be great to have a well-designed randomized controlled trial of patients with atrial fibrillation plus coronary artery disease, comparing clinical outcomes in those assigned to the combo of OAC and antiplatelet therapy with those on OAC alone. So, what is one to do in the absence of a definitive study? given the increased likelihood of very serious consequences of major bleeds on the combo therapy (35% mortality in these events in the current study), it seems reasonable to me that  in those patients who have stable CAD (eg, 1 year after MI or coronary revascularization), the safest route is to use OAC alone... and in those with atrial fibrillation and no documented CAD, not even to consider APT in addition to OAC.