General recommendations regarding antithrombotic therapy in the context of concomitant AF and CAD (asymptomatic, stable CAD, elective PCI, NSTEACS or STEMI):

Recommendation 1 – Antithrombotic therapy based on a balanced assessment of a patient’s risk of stroke (2016)
We recommend that patients who have concomitant AF and CAD receive a regimen of antithrombotic therapy that is based on a balanced assessment of their risks of stroke, of a coronary event and of hemorrhage associated with use of antithrombotic agents (Strong Recommendation, High Quality Evidence).

Recommendation 2 – Most patients with an indication for OAC in the presence of CAD should receive a NOAC (2016)
When OAC is indicated in the presence of CAD, we suggest a NOAC in preference to warfarin for non-valvular AF (Conditional Recommendation, Low Quality Evidence).

Practical tip (2016, updated from 2014)
When CAD is present, some expert clinicians prefer a combination of a NOAC and aspirin rather than NOAC alone in preference to warfarin alone for patients perceived to be at higher risk of coronary events and low risk of major bleeding and may choose a NOAC alone as a reasonable option in those with average to lower risk of coronary events and higher risk of bleeding.

Values and preferences (2016, updated from 2014)
The suggestion for use of a NOAC rather than warfarin places relatively greater weight on the ease of use of NOACs versus warfarin and on the data from RCTs of NOACs versus warfarin for NVAF, showing equal or greater reduction of stroke, equal or less major bleeding, less intracranial bleeding and no net increase in CAD outcomes. It places relatively less weight on the absence of long-term data on the effect of NOACs on coronary outcomes as opposed to the data for efficacy of warfarin.

Practical tip (2016)
In general, the recommended doses of NOACs are the usual doses studied in the RCTs of NVAF. For patients requiring combinations of antiplatelet and OAC agents for concomitant AF and CAD, we suggest that measures be employed to reduce the risk of bleeding, including careful consideration of HAS-BLED risk factors and vigorous efforts to mitigate them; specific measures during invasive procedures (radial access, small-diameter sheaths, early sheath removal from femoral site and minimized use of acute procedural anti-thrombotic therapies); consideration of routine proton pump inhibitor (PPI); avoidance of prasugrel and ticagrelor in conjunction with OAC; the use of warfarin in the lower INR range; consideration of the lower effective doses of NOACs; and delaying non-urgent catheterization until there is clarity about coagulation status and renal function. If the risk of restenosis is relatively low, the option of a BMS rather than a second generation DES should be considered.

For patients with AF, with an indication for primary CAD prevention or stable CAD/arterial vascular disease (peripheral vascular disease or aortic plaque), the selection of antithrombotic therapy should be based on their risk of stroke as follows (Figure 2, from 2016 update):

Recommendation 3 – No antithrombotic therapy for patients with no evidence of manifest CAD/vascular disease (2016)
If the patient has no evidence of CAD/vascular disease and is aged <65 years with no CHADS2 risk factors, we suggest no antithrombotic therapy for stroke prevention (Conditional Recommendation, Moderate Quality Evidence).

Recommendation 4 – ASA for patients with no risks besides CAD/arterial vascular disease (2016)
If the patient has stable CAD/vascular disease and is aged <65 years with no CHADS2 risk factors, we suggest aspirin 81 mg daily (Conditional Recommendation, Moderate Quality Evidence).

Recommendation 5 – OAC therapy for patients ≥ 65 years or CHADS2 ≥ 1 (2016)
If the patient has stable CAD/vascular disease and is aged≥65 or the CHADS2≥1, we recommend OAC therapy alone (Strong Recommendation, High Quality Evidence).

For patients with AF and recent elective PCI, the selection of antithrombotic therapy should be based on their risk of stroke as follows (Figure 3, from 2016 update):

Recommendation 6 (2016, adapted from CCS 2012 Antiplatelet Therapy Guidelines)
If the patient is aged <65 years with no CHADS2 risk factors, we recommend aspirin 81 mg daily indefinitely (Strong Recommendation, High Quality evidence).

Recommendation 7 (2016, adapted from CCS 2012 Antiplatelet Therapy Guidelines)
If the patient is aged <65 years with no CHADS2 risk factors, we recommend clopidogrel 75 mg daily for 12 months in addition to aspirin (Strong Recommendation, High Quality Evidence).

Recommendation 8 (2016, adapted from CCS 2012 Antiplatelet Therapy Guidelines)
If the patient is aged <65 years with no CHADS2 risk factors, we recommend that in patients receiving a bare-metal stent who are unable to tolerate clopidogrel for 12 months (eg, increased risk of bleeding or scheduled noncardiac surgery), the minimum duration of therapy should be 1 month (Strong Recommendation, High-Quality Evidence). We suggest in patients at very high risk of bleeding, the minimum duration of treatment may be 2 weeks (Conditional Recommendation, Low-Quality Evidence).

Recommendation 9 (2016, adapted from CCS 2012 Antiplatelet Therapy Guidelines)
If the patient is aged <65 years with no CHADS2 risk factors, we suggest that in patients receiving a second generation DES who are unable to tolerate clopidogrel for 12 months (eg, increased risk of bleeding or scheduled noncardiac surgery), the minimum duration of therapy may be 3 months (Conditional Recommendation, Low-Quality Evidence).

Recommendation 10 (2016)
If the patient is aged ≥ 65 years or the CHADS₂ ≥1, we suggest that clopidogrel 75 mg daily and OAC be given, without concomitant ASA, for 12 months post-PCI (Conditional Recommendation, Moderate Quality Evidence), to be followed by OAC alone (Strong Recommendation, High Quality Evidence).

Practical Tip (2016)
Some patients who are at high risk of stent thrombosis and whose risk of major bleeding is acceptable may continue OAC + clopidogrel for longer than 12 months post ACS, whereas those at particularly high risk of major bleeding may have their clopidogrel discontinued earlier than 12 months and continue to receive only OAC.

For patients with AF, in association with Non-ST Elevation Acute Coronary Syndrome (NSTEACS) or ST Segment Elevation Myocardial Infarction (STEMI), the selection of antithrombotic therapy should be based on their risk of stroke as follows (Figure 4, from 2016 update):

Recommendation 11 (2016, adapted from CCS 2012 Antiplatelet Therapy Guidelines)
If the patient is aged <65 years with no CHADS2 risk factors, we recommend aspirin 81 mg daily indefinitely (Strong Recommendation, High Quality Evidence).

Recommendation 12 (2016, adapted from CCS 2012 Antiplatelet Therapy Guidelines)
If the patient is aged <65 with no CHADS2 risk factors and no PCI is undertaken, we recommend ticagrelor 90 mg bid for 12 months in addition to ASA in patients with moderate to high risk NSTEACS (defined as ≥ 2 of: 1) ischemic ST changes on ECG, 2) positive biomarkers or 3) any 1 of the following: age ≥ 60 yr, previous MI or CABG, CAD > 50% stenosis in ≥ 2 vessels, previous ischemic stroke, DM, PAD, or CKD) and in most STEMI patients (Strong Recommendation, High Quality Evidence).

Recommendation 13 (2016, adapted from CCS 2012 Antiplatelet Therapy Guidelines)
If the patient is aged <65 with no CHADS2 risk factors and no PCI is undertaken, we recommend clopidogrel 75 mg once daily in addition to ASA for 12 months in lower risk patients and in those judged unsuitable for ticagrelor or when this agent is not available (Strong Recommendation, High Quality Evidence).

Recommendation 14 (2016, adapted from CCS 2012 Antiplatelet Therapy Guidelines)
If the patient is aged <65 years with no CHADS2 risk factors and PCI is undertaken, we recommend ticagrelor 90 mg bid for 12 months in addition to ASA (Strong Recommendation, High Quality Evidence).

Recommendation 15 (2016, adapted from CCS 2012 Antiplatelet Therapy Guidelines)
If the patient is aged <65 years with no CHADS2 risk factors and PCI is undertaken, as an alternative to ticagrelor, we recommend prasugrel 10 mg daily for 12 months in addition to aspirin in P2Y12-naïve patients after their coronary anatomy has been defined and PCI planned. Except in patients with a high probability of undergoing PCI, we recommend delaying prasugrel until the coronary anatomy has been defined and avoiding prasugrel in patients not having PCI (Strong Recommendation, High Quality Evidence).

Recommendation 16 (2016, adapted from CCS 2012 Antiplatelet Therapy Guidelines)
If the patient is aged <65 years with no CHADS2 risk factors and PCI is undertaken, we suggest that for patients prescribed prasugrel and aged ≥ 75 years or weight < 60 kg consideration be given to prasugrel 5 mg daily (Conditional Recommendation, Low Quality Evidence). We recommend avoiding prasugrel in patients with previous TIA or stroke (Strong Recommendation, Moderate Quality Evidence).

Recommendation 17 (2016, adapted from CCS 2012 Antiplatelet Therapy Guidelines)
If the patient is aged <65 years with no CHADS2 risk factors and PCI is undertaken, in patients who are not eligible for ticagrelor or prasugrel, we recommend clopidogrel 75 mg once daily for 12 months in addition to aspirin, and that a dose of 150 mg daily be considered for the first 6 days following PCI (Strong Recommendation, High Quality Evidence).

Recommendation 18 (2016, adapted from CCS 2012 Antiplatelet Therapy Guidelines)
If the patient is aged <65 years with no CHADS2 risk factors and PCI is undertaken, we suggest that some patients with NSTEACS or STEMI, who have undergone PCI, who are at higher risk of stent thrombosis and whose risk of major bleeding is acceptable, may be considered for an ADP receptor antagonist (clopidogrel, prasugrel or ticagrelor) plus aspirin for longer than 12 months post NSTEACS or STEMI (Conditional Recommendation, Low Quality Evidence).

Recommendation 19 (2016, adapted from CCS 2012 Antiplatelet Therapy Guidelines)
If the patient is aged <65 years with no CHADS2 risk factors and PCI is undertaken, we suggest that some patients with NSTEACS or STEMI, who have undergone PCI, at particularly high risk of major bleeding, may have their ADP receptor antagonist discontinued earlier than 12 months post NSTEACS or STEMI and continue to receive only aspirin (Conditional Recommendation, Low Quality Evidence).

Recommendation 20 (2016)
If the patient is aged≥65 or the CHADS2≥1 and no PCI is undertaken, we suggest the combination of clopidogrel 75 mg daily (rather than prasugrel or ticagrelor) and OAC be given, without concomitant ASA, for 12 months, to be followed by OAC alone (Conditional Recommendation, Low Quality Evidence).

Recommendation 21 (2016)
If the patient is aged≥65 or the CHADS2≥1 and PCI is undertaken, we suggest the combination of aspirin 81 mg daily and clopidogrel 75 mg daily and OAC (TT) for 3-6 months (duration depending on the perceived risks of coronary thrombosis and major bleeding). After 3-6 months we suggest the combination of clopidogrel and OAC to be continued until 12 months post-ACS, to be followed by OAC alone (Conditional Recommendation, Low Quality Evidence).

Values and preferences (2016)
The suggestion of TT for the first 3-6 months places greater weight on more reduction of coronary events (versus OAC + clopidogrel) and on more SSE prevented (versus DAPT) but less weight on the increased risk of major bleeding. The balance of stroke/systemic embolus prevented and major bleeds caused could be judged as appropriate only for patients with a higher risk of stroke (e.g. CHADS2≥2).

Practical tip (2016)
Some patients who are at high risk of stent thrombosis and whose risk of major bleeding is acceptable may continue the combination of OAC and clopidogrel for longer than 12 months post ACS.

Practical tip (2016)
Some patients at particularly high risk of major bleeding may have their clopidogrel discontinued earlier than 12 months and continue to receive only OAC.

Practical tip (2016)
Some clinicians may prefer the combination of clopidogrel and OAC beginning from the time of PCI, placing more weight on the reduced bleeding and no increase of thrombotic events compared to TT in the WOEST trial and less value on the fact that only 25% of patients in this trial had PCI for ACS. A combination of aspirin and ticagrelor, or aspirin and prasugrel, or aspirin and clopidogrel may also be used in preference to TT for some patients with CHADS2=1 at the lower end of the stroke risk spectrum (e.g. isolated hypertension), reserving TT or OAC + clopidogrel for patients at higher stroke risk.