Dual Antiplatelet Therapy for Coronary Artery Disease

(Modified September 2023)

Antiplatelet therapy is often used in patients with coronary artery disease (CAD). The chart below provides oral antiplatelet regimen options and durations for CAD indications, including stents. For antiplatelet dosing, cost, and other pertinent information, see our chart, Comparison of Oral Antiplatelets. Intravenous antiplatelet agents or anticoagulants may also be indicated acutely but are not included in this document.

Indication

Antiplatelet Regimen Options

Duration

Note: low-dose aspirin is almost always continued indefinitely in CAD.1

ACS treated with stent

(BMS or DES)
  • Aspirin plus ticagrelor (Brilinta)e (reasonable to use in preference to aspirin plus clopidogrel, except in patients ≥75 years of age undergoing PCI within 24 hours post-fibrinolysis)2

OR

  • Aspirin plus prasugrel (Effient)e (reasonable to use in preference to aspirin plus clopidogrel if patient does not have a history of TIA or stroke). Caution if <60 kg or ≥75 years of age.2

OR

  • Aspirin plus clopidogrel2

See footnote a regarding aspirin dosing.

Note: Ticagrelor or prasugrel prevent about one CV event for every 50 patients treated for one year vs clopidogrel,7,8 but consider cost and side effects.
  • DAPT for at least 12 months (see footnote c), then aspirin indefinitely (DES or BMS).2,24 (see footnote d)
  • Weigh bleeding risk vs thrombosis risk when choosing DAPT duration.2
    • Consider using a bleeding risk calculator. See links in footnote f.
    • There is less data for abbreviated regimens (DAPT ≤6 months) after complex PCI: ≥three vessels/stents/lesions; bifurcation with two stents; total stent length >60 mm, or chronic total occlusion as target lesion.18
    • Studies of abbreviated regimens included few STEMI patients and were underpowered to show differences in stent thrombosis.2,17
  • Abbreviated regimens to reduce bleeding risk [Evidence level B-1]. Unless otherwise noted, studies included ACS and non-ACS patients:
    • P2Y12 inhibitor plus aspirin for one month, then monotherapy (non-inferior to continuation of DAPT for at least two months in patients with high bleeding risk [Precise DAPT ≥25] treated with sirolimus Ultimaster stent; clopidogrel was most commonly used).17
    • Ticagrelor plus aspirin for three months, then ticagrelor monotherapy (see footnote d) (safer and as effective as one year of DAPT in patients with high bleeding or ischemic risk treated with DES).4
    • Ticagrelor plus aspirin for one month, then ticagrelor monotherapy (see footnote d) (safety/efficacy similar to one year of DAPT in patients with biolimus A9 stent).14
    • Ticagrelor plus aspirin for three months , then ticagrelor monotherapy (see footnote d) (safety/efficacy superior to one year of DAPT in ACS treated with sirolimus Orsiro stent).15
    • Clopidogrel plus aspirin for three months, then clopidogrel monotherapy (see footnote d) (noninferior [for major CV events] to one year of DAPT in patients with DES).5
    • Clopidogrel plus aspirin for one to two months, then clopidogrel monotherapy (see footnote d) reduced bleeding events, but noninferior for CV events vs one-year of DAPT in ACS treated with CoCr-EES stent).23
  • If at high risk of bleeding or severe bleeding complication (e.g., oral anticoagulant, major intracranial surgery), or if significant overt bleeding occurs, it may be reasonable to discontinue the P2Y12 inhibitor (clopidogrel, prasugrel, or ticagrelor) after six months and continue aspirin monotherapy.1,2
  • Surgical considerations: delay elective noncardiac surgery for 30 days after BMS placement, and preferably for six months (may consider after three months) after DES placement. Continue aspirin, if possible, and restart P2Y12 inhibitor (i.e., clopidogrel, prasugrel, or ticagrelor) as soon as possible post-op. Consider risk/benefit, with input from all treating clinicians, when making decisions regarding surgery and antiplatelet therapy.1

ACS, medically treated (no fibrinolysis, no revascularization)
  • Aspirin plus ticagrelor (Brilinta)e (reasonable to use in preference to aspirin plus clopidogrel in NSTE-ACS)1

OR

  • Aspirin plus clopidogrel1

See footnote a regarding aspirin dosing.

Note: Ticagrelor prevents about one CV event for every 50 patients treated for one year vs clopidogrel,7 but consider cost and side effects.
  • DAPT for at least 12 months, then aspirin indefinitely.1,24 (see footnote d)
    • If not at high bleeding risk (e.g., no history of bleeding on DAPT, no coagulopathy, no oral anticoagulant use), longer-duration DAPT may be reasonable (e.g., up to 36 months).1,24

STEMI, treated with fibrinolysis
  • Aspirin plus clopidogrel1

See footnote a regarding aspirin dosing.
  • DAPT for at least 14 days, but ideally for at least 12 months, then aspirin indefinitely.1 (see footnote d)
    • If not at high bleeding risk (e.g., no history of bleeding on DAPT, no coagulopathy, no oral anticoagulant use), longer-duration DAPT may be reasonable.1

Stable ischemic heart disease treated with stent (BMS or DES)
  • Aspirin plus clopidogrel1

See footnote a regarding aspirin dosing.
  • BMS: DAPT for at least one month, then aspirin indefinitiely.2 (see footnote d)
    • If not at high bleeding risk (e.g., no history of significant overt bleeding on DAPT, no coagulopathy, no oral anticoagulant use), longer-duration DAPT may be reasonable.1,2
  • DES: DAPT for at least six months (see footnote b), then aspirin indefinitely.1,24 (see footnote d)
  • Weigh bleeding risk vs thrombosis risk when choosing DAPT duration.2
    • Consider using a bleeding risk calculator. See links in footnote f.
    • Abbreviated regimens (DAPT ≤6 months) are riskier after complex PCI: ≥three vessels/stents/lesions; bifurcation with two stents; total stent length >60 mm, or chronic total occlusion as target lesion.18
    • Studies of abbreviated regimens were underpowered to show differences in stent thrombosis.2,17
  • Abbreviated regimens to reduce risk of bleeding [Evidence level B-1]. Unless otherwise noted, studies included ACS and non-ACS patients.
    • P2Y12 inhibitor plus aspirin for one month, then monotherapy (non-inferior to continuation of DAPT for at least two months in patients with high bleeding risk [Precise DAPT ≥25] treated with sirolimus Ultimaster stent; clopidogrel was most commonly used).17
    • Ticagrelor plus aspirin for three months, then ticagrelor monotherapy (see footnote d) (safer and as effective as one year of DAPT in patients with high bleeding or ischemic risk treated with DES).4
    • Ticagrelor plus aspirin for one month, then ticagrelor monotherapy (see footnote d) (safety/efficacy similar to one year of DAPT in patients with biolimus A9 stent).14
    • Clopidogrel plus aspirin for three months, then clopidogrel monotherapy (see footnote d) (noninferior [for major CV events] to one-year of DAPT in patients with DES).5
    • Clopidogrel plus aspirin for one month, then clopidogrel monotherapy (see footnote d) (noninferior to one year of DAPT in patients with CoCr-EES stent).6
  • If at high risk of bleeding or severe bleeding complication (e.g., oral anticoagulant use, major intracranial surgery), or if significant overt bleeding occurs, it may be reasonable to discontinue clopidogrel after three months and continue aspirin monotherapy.1,2
  • Surgical considerations: delay elective noncardiac surgery for 30 days after BMS placement, and preferably for six months (may consider after three months) after DES placement. Continue aspirin, if possible, and restart clopidogrel as soon as possible post-op. Consider risk/benefit, with input from all treating clinicians, when making decisions regarding surgery and antiplatelet therapy.1

Stable ischemic heart disease, with NO history of ACS, stent, or CABG
  • Aspirin monotherapy (do not use DAPT)1,24

See footnote a regarding aspirin dosing.
  • Indefinitely.1,24

Stable ischemic heart disease patient with history of MI one to three years prior
  • DAPT1

OR

  • Aspirin monotherapy1

See footnote a regarding aspirin dosing.
  • Reasonable to continue DAPT if not at high bleeding risk (e.g., no history of bleeding on DAPT, no coagulopathy, no oral anticoagulant use).1
    • DAPT with ticagrelor 60 mg twice daily is approved for use in this situation, based on results of the PEGASUS-TIMI 45 study.1,12 Combo prevented a second MI in one in 139 patients treated over three years vs aspirin alone. Combo caused major bleeding in one in 81 patients. One in 27 patients discontinued ticagrelor due to shortness of breath. Patients in the study had relatively high cardiovascular risk and relatively low bleeding risk.9
  • If DAPT is not continued, continue aspirin monotherapy indefinitely.1 (see footnote d)

CABG

Pre-CABG antiplatelet management for patients on DAPT:

  • Elective CABG: it is reasonable to stop clopidogrel for five days, ticagrelor for three days, and prasugrel for seven days pre-op.2
  • Urgent CABG: hold clopidogrel or ticagrelor for at least 24 hours pre-op.2
  • Continue aspirin until the time of surgery.2

Post-CABG antiplatelets:

  • If a patient being treated with DAPT post-stent undergoes CABG, resume P2Y12 inhibitor as soon as safe post-op for recommended duration (4 weeks to >12 months, as above).1,10 Continue aspirin 100 to 325 mg daily, indefinitely.2 (see footnote d)
  • If a post-ACS patient being treated with DAPT undergoes CABG, resume P2Y12 inhibitor as soon as safe post-op to complete the recommended DAPT duration, as above.1 Continue aspirin 100 to 325 mg daily, indefinitely.2 (see footnote d)
  • In CABG patients who present with ACS, DAPT with prasugrel or ticagrelor is reasonable (and preferred over clopidogrel), for at least 12 months.1,3,e Continue aspirin 100 to 325 mg daily, indefinitely.2  (see footnote d)
  • In patients with stable ischemic heart disease, DAPT (with clopidogrel or ticagrelor) for 12 months post-CABG is reasonable to improve graft patency (most data with clopidogrel, off-pump).2,e Continue aspirin 100 to 325 mg daily, indefinitely.2 (see footnote d)
  • If DAPT is not used, start aspirin 100 to 325 mg daily within six hours post-CABG and continue indefinitely.2 Patients taking warfarin should use an aspirin dose of 75 to 162 mg daily.3 Consider a dose of 325 mg once daily, for at least the first year, for patients not taking warfarin.3,16 If aspirin cannot be used, clopidogrel 75 mg once daily, indefinitely, is a reasonable aspirin alternative.3 (see footnote d)
  1. The recommended aspirin dose is 81 mg (75 to 100 mg) daily when used as part of dual antiplatelet therapy or monotherapy for CAD.1,24 Doses >81 mg daily may not be more effective, while causing more bleeding.1 Use ticagrelor with aspirin 75 to 100 mg daily (Canada: 75 to 150 mg daily). Higher doses may reduce ticagrelor efficacy.11,12
  2. Stable ischemic heart disease treated with stent (DES): If not at high bleeding risk (e.g., no history of bleeding on DAPT, no coagulopathy, no oral anticoagulant use), longer-duration DAPT may be reasonable.1 However, longer durations do not seem to reduce CV events and may increase bleeding risk.13
  3. ACS treated with stent: If NOT at high bleeding risk (e.g., no history of bleeding on DAPT, no coagulopathy, no oral anticoagulant use), longer-duration DAPT may be reasonable (e.g., up to 36 months).1,24 The DAPT risk calculator (http://tools.acc.org/DAPTriskapp/#!/content/calculator/) can help identify patients who might benefit from DAPT continuation beyond one year.
  4. Increasing evidence supports clopidogrel over aspirin for long-term maintenance monotherapy.19-21 Post DES (12+/- 6 months), use of clopidogrel instead of aspirin for ~6 years reduces BARC ≥2 bleeding (NNT = 63), ACS readmission (NNT = 33), any revascularization (NNT = 63), and stroke (NNT =72).19  In patients with CAD, a meta-analysis found that clopidogrel was more effective than aspirin for reducing a composite endpoint of CV death, MI, and stroke (NNT = 133), with similar major bleeding risk.  The primary endpoint was largely driven by a reduction in MI.25
  5. De-escalation from ticagrelor or prasugrel to clopidogrel is often necessary due to cost, side effects, or poor adherence.22 Clopidogrel can be started 24 hours after the last dose of prasugrel or ticagrelor.22 Patients switched from ticagrelor to clopidogrel (or from prasugrel to clopidogrel <30 days post-event/stent) should generally be given a loading dose of clopidogrel 600 mg x 1, but skipping the loading dose and starting with clopidogrel 75 mg once daily is an option, especially if the patient is being switched due to bleeding or if de-escalation is >30 days after the event/PCI.22
  6. Bleeding risk calculator links: Precise DAPT: http://www.precisedaptscore.com/predapt/; Academic Research Consortium High Bleeding Risk evaluator: https://www.cerc-europe.org/arc-hbr-high-bleeding-risk-evaluator/.

Abbreviations: ACS = acute coronary syndrome (i.e., NSTE-ACS or STEMI); BMS = bare metal stent; BARC = Bleeding Academic Research Consortium; CABG = coronary artery bypass graft; CAD = coronary artery disease; CoCR-EES = cobalt-chromium-everolimus-eluting stent; CV = cardiovascular; DAPT = dual antiplatelet therapy; DES = drug-eluting stent; MI = myocardial infarction; NSTE-ACS = non-ST-elevation acute coronary syndrome; P2Y12 inhibitor = clopidogrel, prasugrel, or ticagrelor; PCI = percutaneous coronary intervention; STEMI = ST-elevation MI; TIA = transient ischemic attack.

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.*
  1. High-quality randomized controlled trial (RCT)
  2. Systematic review (SR)/Meta-analysis of RCTs with consistent findings
  3. All-or-none study

B

Inconsistent or limited-quality patient-oriented evidence.*
  1. Lower-quality RCT
  2. SR/Meta-analysis with low-quality clinical trials or of studies with inconsistent findings
  3. Cohort study
  4. 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

  1. Levine GN, Bates ER, Bittl JA, et al. 2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease: a report of the American College of Cardiology/America Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2016 Sep 6;68(10):1082-115.
  2. 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.
  3. Kulik A, Ruel M, Jneid H, et al. Secondary prevention after coronary artery bypass graft surgery: a scientific statement from the American Heart Association. Circulation. 2015 Mar 10;131(10):927-64.
  4. Mehran R, Baber U, Sharma SK, et al.Ticagrelor with or without aspirin in high-risk patients after PCI. N Engl J Med. 2019 Nov 21;381(21):2032-2042.
  5. Hahn J-Y, Song YB, Oh J-H, et al.Effect of P2Y12 inhibitor monotherapy vs dual antiplatelet therapy on cardiovascular events in patients undergoing percutaneous coronary intervention: the SMART-CHOICE randomized clinical trial. JAMA. 2019 Jun 25;321(24):2428-2437.
  6. Watanabe H, Domei T, Morimoto T, et al.Effect of 1-month dual antiplatelet therapy followed by clopidogrel vs 12-month dual antiplatelet therapy on cardiovascular and bleeding events in patients receiving PCI: the STOPDAPT-2 randomized clinical trial. JAMA. 2019 Jun 25;321(24):2414-2427.
  7. Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009 Sep 10;361(11):1045-57.
  8. Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007 Nov 15;357(20):2001-15.
  9. Bonaca MP, Bhatt DL, Cohen M, et al. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med. 2015 May 7;372(19):1791-800.
  10. Valgimigli M, Bueno H, Byrne RA, et al. 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS: the Task Force for dual antiplatelet therapy in coronary artery disease of the European Society of Cardiology (ESC) and of the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2018 Jan 14;39(3):213-260.
  11. Product information for Brilinta. AstraZeneca LP. Wilmington, DE 19850. August 2021.
  12. Product monograph for Brilinta. AstraZeneca Canada Inc. Mississauga, ON L4Y 1M4. January 2022.
  13. Levine GN, Bates ER, Bittl JA, et al. 2016 ACC/AHA duration of dual antiplatelet therapy guideline focused update data supplement. http://jaccjacc.acc.org/Clinical_Document/DAPT_Data_Supplement_1.pdf. (Accessed May 23. 2023).
  14. Vranckx P, Valgimigli M, Juni P, et al.Ticagrelor plus aspirin for 1 month, followed by ticagrelor monotherapy for 23 months vs aspirin plus clopidogrel or ticagrelor for 12 months, followed by aspirin monotherapy for 12 months after implantation of a drug-eluting stent: a multicentre, open-label, randomised superiority trial. Lancet. 2018 Sep 15;392(10151):940-949.
  15. Kim BK, Hong SJ, Cho YH, et al. Effect of ticagrelor monotherapy vs ticagrelor with aspirin on major bleeding and cardiovascular events in patients with acute coronary syndrome: the TICO randomized clinical trial. JAMA. 2020 Jun 16;323(23):2407-2416.
  16. Ferraris VA, Ferraris SP, Moliterno DJ, et al.The Society of Thoracic Surgeons practice guideline series: aspirin and other antiplatelet agents during operative coronary revascularization (executive summary). Ann Thorac Surg. 2005 Apr;79(4):1454-61.
  17. Valgimigli M, Frigoli E, Heg D, et al. Dual Antiplatelet Therapy after PCI in Patients at High Bleeding Risk. N Engl J Med. 2021 Oct 28;385(18):1643-1655.
  18. Giustino G, Chieffo A, Palmerini T, et al. Efficacy and Safety of Dual Antiplatelet Therapy After Complex PCI. J Am Coll Cardiol. 2016 Oct 25;68(17):1851-1864.
  19. Kang J, Park KW, Lee H, et al. Aspirin Versus Clopidogrel for Long-Term Maintenance Monotherapy After Percutaneous Coronary Intervention: The HOST-EXAM Extended Study. Circulation. 2023 Jan 10;147(2):108-117.
  20. Aggarwal D, Bhatia K, Chunawala ZS, et al. P2Y12 inhibitor versus aspirin monotherapy for secondary prevention of cardiovascular events: meta-analysis of randomized trials. Eur Heart J Open. 2022 Mar 21;2(2):oeac019.
  21. Tasoudis PT, Kyriakoulis IG, Sagris D, et al. Clopidogrel Monotherapy versus Aspirin Monotherapy in Patients with Established Cardiovascular Disease: Systematic Review and Meta-Analysis. Thromb Haemost. 2022 Nov;122(11):1879-1887.
  22. Angiolillo DJ, Rollini F, Storey RF, et al. International Expert Consensus on Switching Platelet P2Y12 Receptor-Inhibiting Therapies. Circulation. 2017 Nov 14;136(20):1955-1975.
  23. Watanabe H, Morimoto T, Natsuaki M, et al. Comparison of Clopidogrel Monotherapy After 1 to 2 Months of Dual Antiplatelet Therapy With 12 Months of Dual Antiplatelet Therapy in Patients With Acute Coronary Syndrome: The STOPDAPT-2 ACS Randomized Clinical Trial. JAMA Cardiol. 2022 Apr 1;7(4):407-417.
  24. Writing Committee Members; Virani SS, Newby LK, 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. J Am Coll Cardiol. 2023 Aug 29;82(9)833-955.
  25. Gragnano F, Cao D, Pirondini L, et al. P2Y12 Inhibitor or Aspirin Monotherapy for Secondary Prevention of Coronary Events. J Am Coll Cardiol. 2023 Jul 11;82(2):89-105.

Cite this document as follows: Clinical Resource, Dual Antiplatelet Therapy for Coronary Artery Disease. Pharmacist’s Letter/Prescriber’s Letter. June 2023. [390615]