To provide guidance to clinicians on the management of patients with indications for both antiplatelet and anticoagulant drugs.Patients who have an indication for oral anticoagulation (OAC) can develop separate conditions that would normally be treated with antiplatelet agents. Atrial fibrillation (AF) and acute coronary syndrome (ACS), with or without requirement for percutaneous coronary intervention (PCI), overlap in approximately 20% of patients. Other indications for anticoagulation, such as venous thromboembolism (VTE), mechanical prosthetic heart valves and left ventricular (LV) thrombus, may also co-exist with the need for single or dual antiplatelet therapy (SAPT, DAPT). Recently, low dose rivaroxaban therapy in combination with acetylsalicylic acid (ASA) has demonstrated benefit in patients with coronary artery disease with or without peripheral artery disease.# 
Antithrombotic management of patients requiring combined anticoagulant and antiplatelet therapy necessitates an individualized consideration of thrombotic risk, including stroke, embolism, stent thrombosis, and ACS, as well as bleeding risk (see Tables 1 and 2). The rationale for combining DAPT (P2Y12 inhibitor + ASA) with warfarin or a direct acting anticoagulant (DOAC) is based on suggested benefits in preventing thrombotic events, but the high rates of associated bleeding are a major concern. Recent data have demonstrated reduced bleeding with the use of a P2Y12 inhibitor + DOAC or warfarin (dual pathway therapy) over triple therapy (DAPT + OAC). Although no increased thrombotic risk has been noted with this strategy, individual studies have been underpowered for thrombotic outcomes.

# MANAGEMENT STRATEGY FOR PATIENTS WITH AF REQUIRING PCI AND ANTIPLATELET THERAPY
Treatment algorithms recommended by the Canadian Cardiovascular Society are shown in Figures 1  and 2. The Canadian Cardiovascular Society recommends that patients with AF + PCI should first be stratified according to their risk of stroke or systemic embolism based on CHADS2 plus age. Those at low risk (CHADS2 =0 age  0 or age >= 65, coronary risk is stratified as:
- Elective PCI without high risk features OR - PCI for ACS or elective PCI with high risk features Bleeding risk (see Table 2) should also be considered when determining the duration and type of the antiplatelet therapy (i.e., SAPT or DAPT). Oral anticoagulant (OAC) therapy should be continued throughout unless bleeding is active or risk extreme. Those at high risk of stent thrombosis (see Table 1) and at low bleeding risk may experience more benefit from longer durations of triple therapy, while those at low risk of stent thrombosis and high risk of bleeding (see Table 2) may benefit more from a dual pathway strategy beginning after PCI.   

# MANAGEMENT STRATEGY FOR PATIENTS WITH VTE REQUIRING PCI AND ANTIPLATELET THERAPY
For patients with VTE, oral or parenteral anticoagulation should be prescribed as recommended for those who do not require antiplatelet therapy. For patients in whom extended or indefinite oral anticoagulation is required, use of an agent with the potential for dose reduction can be considered (e.g., rivaroxaban to 10 mg daily or apixaban to 2.5 mg bid when used beyond 6 months). The choice of antiplatelet agent should be focused on minimizing bleeding risk. Clopidogrel is recommended over ticagrelor or prasugrel and the duration of DAPT may be reduced to the shorter recommended periods as outlined above, if it can be done so safely. Patients requiring elective PCI should have the procedure delayed, if possible, until oral or parenteral anticoagulation is no longer required for VTE management or the risk of recurrence with anticoagulant interruption is minimized (see Clinical Guide: Venous Thromboembolism Duration of Therapy).

# MANAGEMENT STRATEGY FOR PATIENTS WITH LV THROMBUS REQUIRING PCI AND ANTIPLATELET THERAPY
Warfarin is the only OAC that has been recommended in patients with LV thrombus. The use of DOACs in patients with LV thrombus is limited to case reports. A recent multicentre retrospective study also suggested that DOAC therapy for LV thrombus was associated with higher rates of stroke or systemic embolism. 

# MANAGEMENT STRATEGY FOR PATIENTS WITH PROSTHETIC HEART VALVES REQUIRING PCI AND ANTIPLATELET THERAPY
In patients with a mechanical heart valve, warfarin is specifically recommended. DOACs are contraindicated. After PCI, the uninterrupted use of warfarin is critical to minimize the risk of valve thrombosis. When patients with mechanical heart valves undergo PCI with or without ACS, triple therapy with OAC, clopidogrel and ASA should be used initially. As with other indications for triple therapy, ASA may be discontinued as early as 1 day post PCI or continued up to 6 months depending on bleeding and thrombotic risk (see Tables 1 and 2).

# LOW DOSE RIVAROXABAN AND ASA IN PATIENTS WITH STABLE CARDIOVASCULAR DISEASE
The risk of recurrent thrombotic events in patients with stable cardiovascular disease remains substantial despite secondary prevention strategies. While the combination of warfarin with standard low dose ASA has been associated with decreased thrombotic event rates, risks of bleeding (including intracranial bleeding) are increased. The Cardiovascular Outcomes for People with using Anticoagulation Strategies (COMPASS) trial randomized patients with stable atherosclerotic vascular disease to receive rivaroxaban 2.5 mg twice daily plus ASA 100 mg daily, rivaroxaban 5 mg twice daily, or ASA 100 mg daily. The combination of rivaroxaban plus ASA resulted in a 1.3% absolute risk reduction in cardiovascular death, stroke, or nonfatal myocardial infarction (24% relative risk reduction), with a trend toward improved mortality. This benefit was offset by a 1.2% increased absolute risk in major bleeding (70% relative risk increase), without any significant difference between the groups with respect to fatal bleeding or intracranial bleeding. Given these results, the addition of rivaroxaban 2.5 mg po twice daily to ASA can be considered in patients with stable cardiovascular disease with a high thrombotic risk that is thought to outweigh the bleeding risks associated with this combination.
Information about the use of low dose rivaroxaban and ASA in patients with peripheral vascular disease can be found in Clinical Guide: Peripheral Arterial Disease.

# LONG-TERM USE OF AN ANTIPLATELET AGENT WITH CONCOMITANT THERAPEUTIC DOSE ANTICOAGULATION
Less data are available to guide clinicians on which patients could benefit by receiving indefinite use of the combination of low dose ASA with a full dose anticoagulant. Potential scenarios include antiphospholipid antibody syndrome (APS), mechanical heart valves, and atrial fibrillation with stable CAD.

# APS:
This syndrome is associated with a significantly elevated risk of both arterial and venous thrombosis. Those patients with this syndrome who develop arterial thrombosis have a higher risk of recurrent thrombotic episodes. Guidelines suggest that the addition of ASA to warfarin may be considered in those patients with APS who experience a recurrent arterial or venous thrombosis despite already being on warfarin and in the target INR range (INR 2-3). It is recommended that all such patients be referred to a thrombosis specialist or hematologist (See Clinical Guide: Thrombophilia: Antiphospholipid Antibody Syndrome).

# Mechanical Heart Valves:
Older randomized studies reported lower rates of systemic embolism and potentially lower rates of death when ASA was added to warfarin in patients with mechanical heart valves. Experts suggest using this combination in this scenario, especially if the patient is at low risk of bleeding or at a high thrombotic risk. (See Clinical Guide: Mechanical and Bioprosthetic Heart Valves: Anticoagulant Therapy).

# Concomitant AF and stable CAD:
Guidelines suggest anticoagulation alone in most patients who have an indication for an anticoagulant (most commonly atrial fibrillation) and are at least 1 year from an ACS or coronary stent implantation. This has been supported by randomized trials that have established warfarin's secondary preventative benefit in stable CAD. In addition, other studies have suggested no difference in the risk of arterial thrombotic events in patients with atrial fibrillation who are on warfarin alone versus combination ASA and warfarin. The AFIRE randomized trial assessed rivaroxaban alone versus the combination of a single antiplatelet agent (70% ASA) with rivaroxaban in Japanese patients with stable CAD and atrial fibrillation. This trial was terminated early due to excess mortality in the combination group. There was less major bleeding and thrombotic events were not significantly different with rivaroxaban alone compared to the combination group. Patients with a history of stent thrombosis were excluded from this trial. Consultation with an expert to develop an antithrombotic regimen is suggested in patients who are at high risk for stent thrombosis.
OTHER RELEVANT THROMBOSIS CANADA CLINICAL GUIDES: 
Please note that the information contained herein is not to be interpreted as an alternative to medical advice from your doctor or other professional healthcare provider. If you have any specific questions about any medical matter, you should consult your doctor or other professional healthcare providers, and as such you should never delay seeking medical advice, disregard medical advice or discontinue medical treatment because of the information contained herein.