Combination Antithrombotic Therapy<br class="t-last-br" />

(Full update April 2024)

Aspirin, P2Y₁₂ inhibitors (clopidogrel, prasugrel, ticagrelor), and oral anticoagulants are commonly prescribed antithrombotic agents. But when they are prescribed in combination, concerns about excess bleeding risk arise. The first chart below addresses frequently asked questions about combination antithrombotic therapy. A second chart (“Summary of Important Combination Therapy Trials”) summarizes studies of combination therapy to help inform decisions regarding your patient.

Question	Answer/Pertinent Information
What is the rationale for prescribing antiplatelet therapy PLUS an anticoagulant?	Platelets play an important role in arterial thrombosis.⁵ Arterial clots form in the high flow conditions of the arterial system, and consist of aggregated platelets held together with fibrin.⁵ Antiplatelet drugs are therefore the primary means of prevention of arterial clots, such as those involved in MI, ischemic stroke, peripheral vascular disease, and stent thrombosis.^1,3,5 Venous clots form in the low-flow conditions of the venous system and consist mostly of fibrin with trapped red blood cells; platelets are not major players here.⁵ Anticoagulants (which prevent fibrin formation by interfering with steps of the clotting cascade) are therefore the primary means of prevention of DVT and PE.^4,5 Anticoagulants are the primary means of prevention of thrombosis due to disordered blood flow in the heart (e.g., A-Fib, mechanical heart valves).^2,5 In summary, patients may need both antiplatelet therapy and an anticoagulant to address multiple thrombotic comorbidities (e.g., coronary artery disease plus A-fib).
What are some common combination antithrombotic therapy scenarios?	DAPT (i.e., aspirin plus a second antiplatelet) is commonly used after: coronary events or revascularization (e.g., ACS, MI, PCI, CABG) See our chart, Dual Antiplatelet Therapy for Coronary Artery Disease, for regimens and duration. acute ischemic stroke DAPT may be appropriate short-term for certain patients with acute ischemic stroke. See our chart, Antiplatelets for Recurrent Ischemic Stroke. Single antiplatelet plus anticoagulant. Examples: in a patient with high CV risk, a dual antithrombotic strategy (e.g., low-dose rivaroxaban or apixaban plus aspirin) may be used to further reduce CV risk over aspirin alone [Evidence level B-1]^18-21 See our chart, Comparison of Oral Anticoagulants for more information. patient with recent CABG, plus A-fib.⁶ DAPT plus anticoagulant. Example: patient with an indication for DAPT (e.g., PCI) also has an indication for an anticoagulant (e.g., A-fib, DVT, PE).
What are some general safety considerations for combination antithrombotic therapy?	Patients should receive gastroprotection (PPI [preferred] or H2blocker).⁶ Individualize treatment decisions to account for ischemic risk, bleeding risk, and reason for combination antithrombotic therapy (e.g., stable CAD vs post-ACS).⁶ A DOAC is often preferred over warfarin due to lower risk of serious bleeding, ease of use, and fast onset of action.⁶ Exceptions include patients with mechanical heart valves, moderate or severe mitral stenosis, severe kidney impairment, or triple-positive antiphospholipid syndrome.^6,13 The preferred P2Y₁₂ inhibitor is clopidogrel because it has the most data and the lowest bleeding risk.^6,13 Ticagrelor can be considered post-ACS.^6,13 Avoid prasugrel.⁶ Bleeding risk can be assessed using tools such as HAS-BLED, HEMORR₂HAGES, or ATRIA. (https://www.jacc.org/doi/suppl/10.1016/j.jacc.2020.09.011/suppl_file/mmc4.pdf). Thrombotic risk is based on the coronary lesion factors, stent factors (e.g., type, number, length, location), and other factors per clinical judgment (e.g., prior MI, extensive atherosclerotic disease).⁶
What evidence supports oral anticoagulant monotherapy in PCI patients?	Evidence supporting use of an oral anticoagulant alone after the first year post-stent includes the AFIRE and OAC-ALONE studies in A-fib patients with stable CAD.^11,17 AFIRE was a randomized, open-label trial comparing rivaroxaban alone or rivaroxaban plus a single antiplatelet >12 months post-PCI or CABG in A-fib patients with stable CAD.¹⁵ Monotherapy was noninferior for efficacy (composite of death, MI, stroke, systemic embolism, and unstable angina requiring revascularization), and superior for major bleeding.¹⁵ OAC-ALONE was a randomized, open-label trial comparing oral anticoagulant monotherapy vs a single antiplatelet >12 months post-PCI in A-fib patients with stable CAD.¹⁶ The study was underpowered, but main findings were: the primary outcome (composite of death, MI, stroke, and systemic embolism) occurred in 15.7% of the monotherapy patients and 13.6% of the dual therapy group (p=0.20 for noninferiority). the secondary outcome (composite of primary outcome and major bleeding) occurred in 19.5% and 19.4% for the monotherapy and dual therapy groups, respectively (p=0.16 for noninferiority). MI occurred in 2.3% vs 1.2%, stroke or systemic embolism occurred in 3.8% vs 5.5%, and major bleeding occurred in 7.8% vs 10.4% in the monotherapy and dual therapy groups, respectively.
What is the general approach to antithrombotic therapy for a patient with A-fib who undergoes PCI?	In general, post-PCI patients will start with a P2Y₁₂ inhibitor (clopidogrel preferred) plus an anticoagulant (DOAC preferred), then may eventually step down to anticoagulant monotherapy.^6,11 Initially, aspirin 81 mg can be added (i.e., triple therapy) until discharge, or continued for up to 30 days if bleeding risk is low and thrombotic risk is high.^6,7,17 For patients taking warfarin, continue aspirin at least until the INR is therapeutic.⁶ The anticoagulant will be continued for A-fib indefinitely.⁶ The duration of P2Y₁₂ inhibitor will vary based on certain patient/procedure factors:⁶ in patients who receive a BMS, the P2Y₁₂ inhibitor will be discontinued after one month.⁶ if bleeding risk is high, in DES patients, consideration can be given to stopping the P2Y₁₂ inhibitor after three months (post-PCI for stable CAD) or after six months (post-PCI for ACS).⁶ if bleeding risk is not high, in DES patients, generally continue the P2Y₁₂ inhibitor for at least 12 months.⁶ For stable ischemic heart disease patients, consideration can be given to switching from a P2Y₁₂ inhibitor to aspirin 81 mg once daily at six months post-PCI.⁶ If thrombotic risk is low, consider oral anticoagulant monotherapy after 12 months.¹⁷ If thrombotic risk is high, and bleeding risk is low, consider continuing clopidogrel or aspirin for >12 months along with the oral anticoagulant.⁶
What is the general approach to antithrombotic therapy for a patient taking an oral anticoagulant for VTE disease who undergoes PCI?	Recommendations regarding management of VTE anticoagulation in PCI are extrapolated from studies of PCI in patients with A-fib.⁶ Before PCI, consider if the anticoagulant is still needed for VTE. If the anticoagulant cannot be discontinued, consider if PCI can be deferred until VTE treatment is complete.⁶For DOACs, be sure to switch from VTE initiation dose to VTE treatment dose when appropriate.⁶ Post-PCI, patients will be restarted on their anticoagulant (DOAC preferred).⁶ Patients will start a P2Y₁₂ inhibitor (clopidogrel preferred) along with their anticoagulant.⁶ The duration of P2Y₁₂ inhibitor will vary based on certain patient/procedure factors.⁶ In patients who receive a BMS for stable CAD, the P2Y₁₂ inhibitor may be discontinued after one month, with the patient remaining on oral anticoagulant monotherapy.⁶ Initially, aspirin 81 mg can be added (i.e., triple therapy) until discharge, or continued for up to 30 days if bleeding risk is low and thrombotic risk is high.^6,17 Further management depends upon whether the patient will continue the oral anticoagulant indefinitely for VTE (i.e., to prevent VTE recurrence), or will stop once VTE treatment is complete.⁶ Time-limited VTE treatment. Once VTE treatment is complete, switch the oral anticoagulant to aspirin.⁶ If bleeding risk is high, in DES patients, consideration can be given to stopping the P2Y₁₂ inhibitor after three months (post-PCI for stable CAD), or after six months (post-PCI for ACS), and continuing monotherapy with only the oral anticoagulant or aspirin (if the oral anticoagulant treatment course is finished).⁶ If bleeding risk is not high, in DES patients, generally continue the P2Y₁₂ inhibitor for six months (post-PCI for stable CAD) or 12 months (post-PCI for ACS) while continuing the oral anticoagulant or aspirin (if the oral anticoagulant course is finished.⁶ After 12 months, follow post-PCI antithrombotic guidelines as for other (i.e., non-VTE) PCI patients.⁶Note that aspirin is preferred over clopidogrel if secondary prevention of VTE is desired.⁶ If an oral anticoagulant will be continued indefinitely for VTE. Consider evidence-based apixaban or rivaroxaban dose reduction after six to 12 months and continue indefinitely.⁶ If bleeding risk is high, in DES patients, consideration can be given to stopping the P2Y₁₂ inhibitor after three months (post-PCI for stable CAD) or six months (post-PCI for ACS).⁶ If bleeding risk is not high, in DES patients, generally continue the P2Y₁₂ inhibitor for at least 12 months.⁶ For stable ischemic heart disease patients post-PCI, consideration can be given to switching from a P2Y₁₂ inhibitor to aspirin 81 mg once daily at six months post-PCI.⁶ If thrombotic risk is low, consider oral anticoagulant monotherapy after 12 months.¹⁷ If thrombotic risk is high, and bleeding risk is low, consider continuing clopidogrel or aspirin for >12 months along with the oral anticoagulant.⁶
What is the general approach to antithrombotic therapy for a patient taking an antiplatelet(s) who then requires an oral anticoagulant for VTE treatment or A-fib?	Antiplatelet management will depend on the indication for the antiplatelet.⁶ Generally, if the patient is taking an antiplatelet for primary prevention of CV events, discontinue the antiplatelet when the oral anticoagulant is started for VTE:⁶ For VTE or A-fib treatment after PCI:⁶ if it has been ≤6 months post-DES or <1 month post-BMS: for stable CAD, stop aspirin, but continue P2Y12 inhibitor (clopidogrel preferred) when oral anticoagulant is started.⁶(If thrombotic risk is high, but bleeding risk is low, aspirin 81 mg once daily can be continued [as part of triple therapy] for up to 30 days.^6,7) if it has been six to 12 months post-DES, or one to 12 months post-BMS: for stable CAD, continue aspirin or P2Y12 inhibitor (clopidogrel preferred) when oral anticoagulant is started.⁶ if it has been >12 months post-PCI: stop the antiplatelet(s) when the oral anticoagulant is started. (If thrombotic risk is high, but bleeding risk is low, a single antiplatelet could be continued with the oral anticoagulant.)⁶ For VTE or A-fib treatment in patients with a history of ACS: if it has been ≤12 months since the ACS event, stop aspirin but continue the P2Y₁₂ inhibitor (clopidogrel preferred) when the oral anticoagulant is started.⁶ (If thrombotic risk is high, but bleeding risk is low, aspirin 81 mg once daily can be continued [as part of triple therapy] for up to 30 days.⁶) if it has been >12 months since the event, stop the antiplatelet(s) when the oral anticoagulant is started.⁶(If thrombotic risk is high, but bleeding risk is low, a single antiplatelet can be continued with the oral anticoagulant).⁶ For VTE or A-fib treatment in patients with cerebrovascular disease: for patients with no history of an event or intervention, stop the antiplatelet when the oral anticoagulant is started.⁶ (If thrombotic risk is high, but bleeding risk is low, the antiplatelet can be continued with the oral anticoagulant).⁶ if a carotid stent has been placed: continue antiplatelet therapy for the recommended duration (e.g., one to three months), but stop aspirin and continue the P2Y12 inhibitor (clopidogrel preferred) when the oral anticoagulant is started.⁶(If thrombotic risk is high, but bleeding risk is low, aspirin 81 mg once daily can be continued [as part of triple therapy] for up to 30 days.⁶) For VTE or A-fib treatment in patients with peripheral vascular disease: if medically managed (no interventions), antiplatelet therapy can be stopped when the oral anticoagulant is started.⁶ for endovascular interventions, manage as for carotid stents, above.⁶ if the patient has had surgical repair, stop the antiplatelet when the oral anticoagulant is started.⁶ (If thrombotic risk is high, but bleeding risk is low, the antiplatelet can be continued with the oral anticoagulant).⁶ For VTE or A-fib treatment in patients with stable ischemic heart disease: if there is no history of ACS or revascularization, stop the antiplatelet when the anticoagulant is started.⁶ if the patient has no history of ACS, but has had CABG, stop the antiplatelet when the anticoagulant is started if it has been >1 year since the CABG.⁶Continue aspirin (<100 mg) if it has been <1 year post-CABG.⁶
What is the general approach when a patient with a mechanical heart valve has an indication for antiplatelet therapy?	Information is more limited; individualize treatment decisions.^22,23

Summary of Select Combination Antithrombotic Therapy Trials

Study Participant Characteristics	Triple Therapy Outcomes ([warfarin or DOAC] + aspirin + clopidogrel)	Other regimen(s) Outcomes	Study highlights, other comments
ENTRUST-AF PCI A-fib, PCI for ACS or stable CAD:¹² N = 1,506	Warfarin + P2Y₁₂ inhibitor + aspirin:¹² Bleeding (major or clinically relevant nonmajor): 20% CV death, stroke, MI, SEE, stent thrombosis (composite): 6%¹²	Edoxaban + P2Y₁₂ inhibitor:¹² Bleeding (major or clinically relevant nonmajor): 17% CV death, stroke, MI, SEE, stent thrombosis (composite): 7.3%¹²	Edoxaban-based dual therapy was noninferior to warfarin-based triple therapy in regard to bleeding, with no difference in ischemic events.¹² Randomized, open-label.¹²
WOEST Anticoagulation (69% A-fib), PCI for ACS or stable CAD (~66% DES):⁸ N = 573 Mean age = 70	Warfarin + clopidogrel + aspirin:⁸ Bleeding events: 44.4% Death: 6.3%⁸	Warfarin + clopidogrel:⁸ Bleeding events: 19.4% Death: 2.5%	There was no difference in stent thrombosis, but an increased risk of death (p=0.027, NNT=26) and bleeding events (p<0.0001) with triple therapy compared to dual therapy.⁸ Randomized, open-label.⁸
PIONEER AF-PCI A Fib, PCI for stable CAD or ACS (~67% DES):⁹ N=2,124 Thrombosis prevention was not a primary end point.	Very low-dose rivaroxaban (2.5 mg BID) + dual antiplatelet:⁹ Bleeding: 18% Warfarin + dual antiplatelet:⁹ Bleeding: 26.7%	Low-dose rivaroxaban (15 mg daily) + P2Y₁₂ inhibitor:⁹ Bleeding: 16.8% Major CV events: ~6% in all groups (p>0.05).⁹	Low-dose rivaroxaban plus a P2Y₁₂ inhibitor for 12 months or very-low-dose rivaroxaban plus DAPT was associated with a lower rate of clinically significant bleeding than was standard triple therapy (p<0.001).⁹ In over 90% of patients, the P2Y₁₂ inhibitor used was clopiodgrel.⁹ Randomized, open-label.
Anticoagulation patients post-stent (DES):¹⁴ N = 614	Six weeks of triple therapy:¹⁴ Death: 4.6% (NS) Stent thrombosis: 0% Major bleeding: 5.3%	Six months of triple therapy:¹⁴ Death: 6.4% (NS) Stent thrombosis: 0% Major bleeding: 4%	Neither ischemic complications, nor major bleeding were different between the treatment groups.¹⁴
RE-DUAL PCI A Fib, PCI for ACS or stable CAD (82.6% DES)¹⁰ N=2,725 Thrombosis prevention was not a primary end point.	Warfarin + DAPT:¹⁰(aspirin was discontinued after one to three months) Major or clinically relevant nonmajor bleeding: 26.9%. INR in-range 64% of the time.	Dabigatran + clopidogrel or ticagrelor:¹⁰ Major or clinically relevant nonmajor bleeding: 15.4% (dabigatran 110 mg BID) Secondary efficacy end point of thromboembolic events, death, or unplanned revascularization was similar (about 13%) between groups.¹⁰	88% of patients received clopidogrel; 12% of patients received ticagrelor.¹⁰ Dabigatran 150 mg BID was also studied, but outside the US, patients ≥80 years of age (≥70 years of age in Japan) could be randomized only to dabigatran 110 mg BID or triple therapy. The bleeding end point occurred in 20.2% of patients in the 150 mg BID group.¹⁰
AUGUSTUS A Fib, ACS or PCI⁷ N=4,614 ACS with PCI = 37.3% ACS w/o PCI = 23.9% Elective PCI = 38.8% Thrombosis prevention was not a primary end point.	Apixaban + P2Y₁₂ inhibitor +/- aspirin:⁷ Major or clinically relevant nonmajor bleeding: 13.8% w/aspirin, 7.3% without aspirin Warfarin + P2Y₁₂ inhibitor +/-aspirin:⁷ Major or clinically relevant nonmajor bleeding: 18.7% with aspirin, 10.9% without aspirin.INR in-range 54% of the time.	Secondary end point of death or hospitalization: lower incidence of hospitalization in the apixaban group.⁷ Secondary end point of death or ischemic events: no difference between apixaban and warfarin.⁷	In 92.6% of patients, the P2Y₁₂ inhibitor used was clopidogrel.⁷ Apixaban dose 5 mg BID (2.5 mg BID with two or more of the following: age ≥80 years, SCr ≥1.5 mg/dL [133 umol/L], or weight ≤60 kg).⁷ NNT to prevent one bleeding event with apixaban instead of warfarin = 24 over six months.⁷ NNT to prevent one death or hospitalization with apixaban instead of warfarin = 26 over six months.⁷ This is the first study to examine whether reduced bleeding with a DOAC is due to absence of aspirin from the regimen or use of a DOAC.⁷ Placebo-controlled.⁷

Study Participant Characteristics

Triple Therapy Outcomes

([warfarin or DOAC] + aspirin + clopidogrel)

Other regimen(s) Outcomes

Study highlights, other comments

ENTRUST-AF PCI

A-fib, PCI for ACS or stable CAD:¹²

N = 1,506

Warfarin + P2Y₁₂ inhibitor + aspirin:¹²

Bleeding (major or clinically relevant nonmajor): 20%

CV death, stroke, MI, SEE, stent thrombosis (composite): 6%¹²

Edoxaban + P2Y₁₂ inhibitor:¹²

Bleeding (major or clinically relevant nonmajor): 17%

CV death, stroke, MI, SEE, stent thrombosis (composite): 7.3%¹²

Edoxaban-based dual therapy was noninferior to warfarin-based triple therapy in regard to bleeding, with no difference in ischemic events.¹²
Randomized, open-label.¹²

WOEST

Anticoagulation (69% A-fib), PCI for ACS or stable CAD (~66% DES):⁸

N = 573

Mean age = 70

Warfarin + clopidogrel + aspirin:⁸

Bleeding events: 44.4%

Death: 6.3%⁸

Warfarin + clopidogrel:⁸

Bleeding events: 19.4%

Death: 2.5%

There was no difference in stent thrombosis, but an increased risk of death (p=0.027, NNT=26) and bleeding events (p<0.0001) with triple therapy compared to dual therapy.⁸
Randomized, open-label.⁸

PIONEER AF-PCI

A Fib, PCI for stable CAD or ACS (~67% DES):⁹

N=2,124

Thrombosis prevention was not a primary end point.

Very low-dose rivaroxaban
(2.5 mg BID) + dual

antiplatelet:⁹

Bleeding: 18%

Warfarin + dual antiplatelet:⁹

Bleeding: 26.7%

Low-dose rivaroxaban (15 mg daily) + P2Y₁₂ inhibitor:⁹

Bleeding: 16.8%

Major CV events: ~6% in all groups (p>0.05).⁹

Low-dose rivaroxaban plus a P2Y₁₂ inhibitor for 12 months or very-low-dose rivaroxaban plus DAPT was associated with a lower rate of clinically significant bleeding than was standard triple therapy (p<0.001).⁹
In over 90% of patients, the P2Y₁₂ inhibitor used was clopiodgrel.⁹
Randomized, open-label.

Anticoagulation patients post-stent (DES):¹⁴

N = 614

Six weeks of triple therapy:¹⁴

Death: 4.6% (NS)

Stent thrombosis: 0%

Major bleeding: 5.3%

Six months of triple therapy:¹⁴

Death: 6.4% (NS)

Stent thrombosis: 0%

Major bleeding: 4%

Neither ischemic complications, nor major bleeding were different between the treatment groups.¹⁴

RE-DUAL PCI

A Fib, PCI for ACS or stable CAD (82.6% DES)¹⁰

N=2,725

Thrombosis prevention was not a primary end point.

Warfarin + DAPT:¹⁰(aspirin was discontinued after one to three months)

Major or clinically relevant nonmajor bleeding: 26.9%. INR in-range 64% of the time.

Dabigatran + clopidogrel or ticagrelor:¹⁰

Major or clinically relevant nonmajor bleeding: 15.4% (dabigatran 110 mg BID)

Secondary efficacy end point of thromboembolic events, death, or unplanned revascularization was similar (about 13%) between groups.¹⁰

88% of patients received clopidogrel; 12% of patients received ticagrelor.¹⁰
Dabigatran 150 mg BID was also studied, but outside the US, patients ≥80 years of age (≥70 years of age in Japan) could be randomized only to dabigatran 110 mg BID or triple therapy. The bleeding end point occurred in 20.2% of patients in the 150 mg BID group.¹⁰

AUGUSTUS

A Fib, ACS or PCI⁷

N=4,614

ACS with PCI = 37.3%

ACS w/o PCI = 23.9%

Elective PCI = 38.8%

Thrombosis prevention was not a primary end point.

Apixaban + P2Y₁₂ inhibitor +/- aspirin:⁷

Major or clinically relevant nonmajor bleeding: 13.8% w/aspirin, 7.3% without aspirin

Warfarin + P2Y₁₂ inhibitor +/-aspirin:⁷

Major or clinically relevant nonmajor bleeding: 18.7% with aspirin, 10.9% without aspirin.INR in-range 54% of the time.

Secondary end point of death or hospitalization: lower incidence of hospitalization in the apixaban group.⁷

Secondary end point of death or ischemic events: no difference between apixaban and warfarin.⁷

In 92.6% of patients, the P2Y₁₂ inhibitor used was clopidogrel.⁷
Apixaban dose 5 mg BID (2.5 mg BID with two or more of the following: age ≥80 years, SCr ≥1.5 mg/dL [133 umol/L], or weight ≤60 kg).⁷
NNT to prevent one bleeding event with apixaban instead of warfarin = 24 over six months.⁷
NNT to prevent one death or hospitalization with apixaban instead of warfarin = 26 over six months.⁷
This is the first study to examine whether reduced bleeding with a DOAC is due to absence of aspirin from the regimen or use of a DOAC.⁷
Placebo-controlled.⁷

Abbreviations: ACS = acute coronary syndrome; A-fib = atrial fibrillation; BMS = bare metal stent; CABG = coronary artery bypass graft; CAD = coronary artery disease; CV = cardiovascular; DAPT = dual antiplatelet therapy; DES = drug-eluting stent; DOAC = direct-acting oral anticoagulant; DVT = deep venous thrombosis; MI = myocardial infarction; PCI = percutaneous coronary intervention; PE = pulmonary embolism; PPI = proton pump inhibitor; SCr = serum creatinine; SEE = systemic embolic event; VTE = venous thromboembolism

Levels of Evidence

In accordance with our goal of providing Evidence-Based information, we are citing the LEVEL OF EVIDENCE for the clinical recommendations we publish.

Level	Definition	Study Quality
A	Good-quality patient-oriented evidence.*	High-quality randomized controlled trial (RCT) Systematic review (SR)/Meta-analysis of RCTs with consistent findings All-or-none study
B	Inconsistent or limited-quality patient-oriented evidence.*	Lower-quality RCT SR/Meta-analysis with low-quality clinical trials or of studies with inconsistent findings Cohort study Case control study
C	Consensus; usual practice; expert opinion; disease-oriented evidence (e.g., physiologic or surrogate endpoints); case series for studies of diagnosis, treatment, prevention, or screening.

*Outcomes that matter to patients (e.g., morbidity, mortality, symptom improvement, quality of life).

[Adapted from Ebell MH, Siwek J, Weiss BD, et al. Strength of Recommendation Taxonomy (SORT): a patient-centered approach to grading evidence in the medical literature. Am Fam Physician 2004;69:548-56. https://www.aafp.org/pubs/afp/issues/2004/0201/p548.html.]

References

Ashorobi D, Ameer MA, Fernandez R. Thrombosis. 2023 Aug 8. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan–.
Roudaut R, Serri K, Lafitte S. Thrombosis of prosthetic heart valves: diagnosis and therapeutic considerations. Heart. 2007 Jan;93(1):137-42.
Grove ECL, Kristensen SD. Stent thrombosis: definitions, mechanisms and prevention. E-jounral of Cardiology Practice 2007;5(32). https://www.escardio.org/Journals/E-Journal-of-Cardiology-Practice/Volume-5/Stent-thrombosis-definitions-mechanisms-and-prevention-Title-Stent-thrombos. (Accessed March 1, 2024).
Shapiro NL, Hellenbart EL. Thrombosis. In: Zeind CS, Carvalho MG, editors. Applied Therapeutics: the Clinical Use of Drugs. 11th ed. Philadelphia, PA: Wolters Kluwer Health, 2018: 174-208.
Weitz JI, Eikelboom JW, Samama MM. New antithrombotic drugs: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e120S-e151S.
Kumbhani DJ, Cannon CP, Beavers CJ, et al. 2020 ACC Expert Consensus Decision Pathway for Anticoagulant and Antiplatelet Therapy in Patients With Atrial Fibrillation or Venous Thromboembolism Undergoing Percutaneous Coronary Intervention or With Atherosclerotic Cardiovascular Disease: A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2021 Feb 9;77(5):629-658.
Lopes RD, Heizer G, Aronson R, et al. Antithrombotic Therapy after Acute Coronary Syndrome or PCI in Atrial Fibrillation. N Engl J Med. 2019 Apr 18;380(16):1509-1524.
Dewilde WJ, Oirbans T, Verheugt FW, et al. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial. Lancet. 2013 Mar 30;381(9872):1107-15.
Gibson CM, Mehran R, Bode C, Prevention of Bleeding in Patients with Atrial Fibrillation Undergoing PCI. N Engl J Med. 2016 Dec 22;375(25):2423-2434.
Cannon CP, Bhatt DL, Oldgren J, et al. Dual Antithrombotic Therapy with Dabigatran after PCI in Atrial Fibrillation. N Engl J Med. 2017 Oct 19;377(16):1513-1524.
Joglar JA, Chung MK, Armbruster AL, et al. 2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2024 Jan 2;149(1):e1-e156. Erratum in: Circulation. 2024 Jan 2;149(1):e167. Erratum in: Circulation. 2024 Feb 27;149(9):e936.
Vranckx P, Valgimigli M, Eckardt L et al. Edoxaban-based versus vitamin K antagonist-based antithrombotic regimen after successful coronary stenting in patients with atrial fibrillation (ENTRUST-AF PCI): a randomised, open-label, phase 3b trial. Lancet. 2019 Oct 12;394(10206):1335-1343.
Angiolillo DJ, Goodman SG, Bhatt DL, et al. Antithrombotic Therapy in Patients With Atrial Fibrillation Treated With Oral Anticoagulation Undergoing Percutaneous Coronary Intervention: A North American Perspective-2018 Update. Circulation. 2018 Jul 31;138(5):527-536.
Fiedler KA, Maeng M, Mehilli J, et al. Duration of Triple Therapy in Patients Requiring Oral Anticoagulation After Drug-Eluting Stent Implantation: The ISAR-TRIPLE Trial. J Am Coll Cardiol. 2015 Apr 28;65(16):1619-1629.
Yasuda S, Kaikita K, Akao M, et al. Antithrombotic Therapy for Atrial Fibrillation with Stable Coronary Disease. N Engl J Med. 2019 Sep 19;381(12):1103-1113. Epub 2019 Sep 2. Erratum in: N Engl J Med. 2021 Oct 21;385(17):1632.
Matsumura-Nakano Y, Shizuta S, Komasa A, et al. Open-Label Randomized Trial Comparing Oral Anticoagulation With and Without Single Antiplatelet Therapy in Patients With Atrial Fibrillation and Stable Coronary Artery Disease Beyond 1 Year After Coronary Stent Implantation. Circulation. 2019 Jan 29;139(5):604-616.
Virani SS, Newby LK, Arnold SV, et al. 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. Circulation. 2023 Aug 29;148(9):e9-e119. Erratum in: Circulation. 2023 Sep 26;148(13):e148. Erratum in: Circulation. 2023 Dec 5;148(23):e186.
Bhatt DL, Eikelboom JW, Connolly SJ, et al. Role of Combination Antiplatelet and Anticoagulation Therapy in Diabetes Mellitus and Cardiovascular Disease: Insights From the COMPASS Trial. Circulation. 2020 Jun 9;141(23):1841-1854.
Mega JL, Braunwald E, Wiviott SD, et al. Rivaroxaban in patients with a recent acute coronary syndrome. N Engl J Med. 2012 Jan 5;366(1):9-19.
Alexander JH, Lopes RD, James S, et al. Apixaban with antiplatelet therapy after acute coronary syndrome. N Engl J Med. 2011 Aug 25;365(8):699-708.
Chiarito M, Cao D, Cannata F, et al. Direct Oral Anticoagulants in Addition to Antiplatelet Therapy for Secondary Prevention After Acute Coronary Syndromes: A Systematic Review and Meta-analysis. JAMA Cardiol. 2018 Mar 1;3(3):234-241. Erratum in: JAMA Cardiol. 2018 May 1;3(5):445.
Otto CM, Nishimura RA, Bonow RO, et al. 2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2021 Feb 2;143(5):e35-e71. Erratum in: Circulation. 2021 Feb 2;143(5):e228. Erratum in: Circulation. 2021 Mar 9;143(10):e784.
Lawton JS, Tamis-Holland JE, Bangalore S,. et al. 2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022 Jan 18;145(3):e18-e114. Erratum in: Circulation. 2022 Mar 15;145(11):e772.

Cite this document as follows: Clinical Resource, Combination Antithrombotic Therapy. Pharmacist’s Letter/Pharmacy Technician’s Letter/Prescriber Insights. April 2024. [400461]

Combination Antithrombotic Therapy

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