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dual antiplatelet therapy (DAPT)

Indications: - following coronary stent (one year of therapy) - 6-12 months for drug-eluting stent [11] - 3 months may be reasonable in patients with high risk of bleeding [11] - > 1 month for bare metal stent - following acute coronary syndrome or MI (STEMI, NSTEMI) - >= 12 months of therapy [11] - patients with stable CAD undergoing CABG - 12 months of therapy Contraindications: - secondary prevention of cardiovascular events [6] - patients with diabetes mellitus & coronary artery disease [20] - chronic stable angina in the absence of revascularization [21] Benefit/risk: - for 1 year following coronary stent - no mortality benefit [5] - number needed to treat (NNT) to prevent 1 non-fatal MI or 1 stroke = 27 [5] - number need to harm (major hemorrhage) = 117 - no benefit for secondary prevention of cardiovascular events [6] - reduces risk of new stroke after TIA or ischemic stroke at cost of increased risk of bleeding vs aspirin alone [22] - 1-3 weeks of DAPT after TIA or ischemic stroke [24] - benefits of DAPT are front-loaded, bleeding risks are constant [24] Pharmacology: - therapy with two antiplatelet agents generally clopidogrel & aspirin - low-dose aspirin (75-100 mg/day) in all regimens [11] - it seems persantine & aspirin would also qualify, though these two agents are less commonly associated with the term DPAT - ticagrelor may be preferred to clopidogrel after acute coronary syndrome without stent [11] Adverse events: - risk of hemorrhage* (resulting in emergency department visit) associated with dual antiplatelet therapy is less than that for warfarin (3.7 vs 1.2 per 1000 outpatient prescription visits) - nuisance bleeding is common during the first year after MI, & adversely affects quality of life [2] - DAPT for > 12 months associated with higher rate of bleeding- related mortality (RR=0.1.5), but lower rate of myocardial infarction (RR=0.75) than DAPT for < 12 months [14] - all-cause mortality also higher with > 12 months DAPT (RR=1.2) - long-term DAPT (> 12 months) associated with decreased risks for myocardial infarction & stent thrombosis but increased risks for noncardiac death &major bleeding relative to short-term DAPT (< 6 months) [19] - 1-3 months of dual anti-platelet therapy sufficient after PCI with drug-eluting coronary stent [18] - dual antiplatelet therapy increases risk of systemic bleeding after ischemic stroke ~5-6 events per 100 patient-years relative to monotherapy [15], but may not increase risk of intracerebral hemorrhage [15] - dual antiplatelet therapy for ischemic stroke or TIA in patients with low LDL-cholesterol further increases risk of systemic bleeding [23] * proton pump inhibitor provides protection from GI bleeding without affecting adverse cardiovascular risk [11] Management: - duration of therapy is usually 6-12 months [10] - 12 months of dual antiplatelet therapy after PCI with drug- eluting stent is the standard of care [7] - 3-6 months of dual antiplatelet therapy is associated with less bleeding but no difference in ischemia or thrombosis relative to 12 months of therapy [7] - > 6 months of dual antiplatelet therapy is associated with fewer MIs but more bleeding & more deaths relative to < 6 months of therapy, but absolute risk is low (0.03% for MI) [8]* - 12 months of therapy does not decrease risk of myocardial infarction, cardiac death or stent thrombosis & increases risk of bleeding relative to 6 months of therapy with or without type 2 diabetes [13] - 6 months of DAPT after drug-eluting stent for STEMI non-inferior to 12 months of DAPT [16] - mortality benefit for prolonged dual antiplatelet therapy is unlikely [3] - Dual Antiplatelet therapy score (DAPT score) may predict patients that might benefit from prolonged dual antiplatelet therapy - elective non-cardiac surgery should be delayed at least 30 days after bare metal stent implantion & 6 months after drug-eluting stent implantation (i.e. after DAPT is complete) [11] * calculator to predict risks of ischemic events vs bleeding for continued DAPT therapy beyond 1 year after coronary stent placement [9]

Related

antiplatelet agent Dual AntiPlatelet Therapy score (DAPT score)

General

pharmacologic therapy

References

  1. Shehab N et al National Estimates of Emergency Department Visits for Hemorrhage-Related Adverse Events From Clopidogrel Plus Aspirin and From Warfarin Arch Intern Med. 2010;170(21):1926-1933 PMID: 21098354 http://archinte.ama-assn.org/cgi/content/abstract/170/21/1926
  2. Amin AP et al. Nuisance bleeding with prolonged dual antiplatelet therapy after acute myocardial infarction and its impact on health status. J Am Coll Cardiol 2013 May 28; 61:2130 PMID: 23541975 - Dauerman HL. The softer side of bleeding. J Am Coll Cardiol 2013 May 28; 61:2139. PMID: 23541969
  3. Brett AS The Pros and Cons of Dual Antiplatelet Therapy. NEJM Journal Watch. Feb 26, 2015 Massachusetts Medical Society (subscription needed) http://www.jwatch.org - Mauri L et al. Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents. N Engl J Med 2014 Dec 4; 371:2155. PMID: 25399658 http://www.nejm.org/doi/full/10.1056/NEJMoa1409312 - Colombo A and Chieffo A. Dual antiplatelet therapy after drug-eluting stents - How long to treat? N Engl J Med 2014 Dec 4; 371:2225. PMID: 25399657 http://www.nejm.org/doi/full/10.1056/NEJMe1413297 - Gilard M et al. Six-month versus 24-month dual antiplatelet therapy after implantation of drug eluting stents in patients non-resistant to aspirin: ITALIC, a randomized multicenter trial. J Am Coll Cardiol. 2014 Nov 16. pii: S0735-1097(14)06970-8 PMID: 25461690 - Gilard M et al. 6- versus 24-month dual antiplatelet therapy after implantation of drug-eluting stents in patients nonresistant to aspirin: The randomized, multicenter ITALIC trial. J Am Coll Cardiol 2015 Mar 3; 65:777. PMID: 25461690 http://www.sciencedirect.com/science/article/pii/S0735109714069708 - Elmariah S et al. Extended duration dual antiplatelet therapy and mortality: A systematic review and meta-analysis. Lancet 2014 Nov 16 PMID: 25467565 http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2814%2962052-3/abstract
  4. Bonaca MP et al Long-Term Use of Ticagrelor in Patients with Prior Myocardial Infarction. N Engl J Med. March 14, 2015 PMID: 25773268 http://www.nejm.org/doi/full/10.1056/NEJMoa1500857 - Keaney JF Jr Balancing the Risks and Benefits of Dual Platelet Inhibition. N Engl J Med. March 14, 2015 PMID: 25773507 http://www.nejm.org/doi/full/10.1056/NEJMe1502137
  5. The NNT: Clopidogrel Added To Aspirin During and After a Coronary Event or a Stent Procedure. http://www.thennt.com/nnt/clopidogrel-added-to-aspirin-during-and-after-a-coronary-event-or-stenting/
  6. The NNT: Clopidogrel Added to Aspirin to Prevent a Second Heart Attack Or Stroke. http://www.thennt.com/nnt/clopidogrel-with-aspirin-for-prevention-after-prior-heart-attack-or-stroke/ - Squizzato A, Keller T, Romualdi E, Middeldorp S Clopidogrel plus aspirin versus aspirin alone for preventing cardiovascular disease. Cochrane Database Syst Rev. 2011 Jan 19;(1):CD005158 PMID: 21249668 - Bowry AD, Brookhart MA, Choudhry NK. Meta-analysis of the efficacy and safety of clopidogrel plus aspirin as compared to antiplatelet monotherapy for the prevention of vascular events. Am J Cardiol. 2008 Apr 1;101(7):960-6 PMID: 18359315
  7. Navarese EP et al. Optimal duration of dual antiplatelet therapy after percutaneous coronary intervention with drug eluting stents: Meta-analysis of randomised controlled trials. BMJ 2015 Apr 16; 350:h1618. PMID: 25883067 http://www.bmj.com/content/350/bmj.h1618
  8. Spencer FA et al Longer Versus Shorter Duration Dual-Antiplatelet Therapy After Drug-Eluting Stent Placement: A Systematic Review and Meta- analysis. Ann Intern Med. May 26, 2015 PMID: 26005909 http://annals.org/article.aspx?articleid=2297227
  9. Yeh RW, Secemsky E, Kereiakes DJ Individualizing Treatment Duration of Dual Antiplatelet Therapy After Percutaneous Coronary Intervention: An Analysis of the DAPT Study. American Heart Association. 2015 Annual Meeting. Nov 10. http://www.abstractsonline.com/pp8/#!/3795/presentation/47453 - DAPT Score Calculator http://www.daptstudy.org/for-clinicians/score_calculator.htm
  10. 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/ American Heart Association Task Force on Clinical Practice Guidelines: An Update of the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention, 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery, 2012 ACC/AHA/ACP/ AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease, 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction, 2014 AHA/ACC Guideline for the Management of Patients With Non-ST-Elevation Acute Coronary Syndromes, and 2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery. Circulation. March 29, 2016 PMID: 27026020 http://circ.ahajournals.org/content/early/2016/03/28/CIR.0000000000000404.full.pdf+html - Yeh RW, Secemsky EA, Kereiakes DJ et al Development and Validation of a Prediction Rule for Benefit and Harm of Dual Antiplatelet Therapy Beyond 1 Year After Percutaneous Coronary Intervention. JAMA. Published online March 29, 2016. PMID: 27022822 http://jama.jamanetwork.com/article.aspx?articleid=2508253
  11. 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/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2016 Sep 6;68(10):1082-115 PMID: 27036918 Free full text
  12. Vaduganathan M et al. Proton-pump inhibitors reduce gastrointestinal events regardless of aspirin dose in patients requiring dual antiplatelet therapy. J Am Coll Cardiol 2016 Mar 16 PMID: 27012778
  13. Gargiulo G, Windecker S, da Costa BR et al Short term versus long term dual antiplatelet therapy after implantation of drug eluting stent in patients with or without diabetes: systematic review and meta-analysis of individual participant data from randomised trials. BMJ 2016;355:i5483 PMID: 27811064 Free full text http://www.bmj.com/content/355/bmj.i5483 - Ball J Optimal duration of dual antiplatelet therapy after stent implantation in patients with or without diabetes. BMJ 2016;355:i5730 PMID: 27811234 http://www.bmj.com/content/355/bmj.i5730
  14. Palmerini T, Bacchi Reggiani L et al. Bleeding-related deaths in relation to the duration of dual- antiplatelet therapy after coronary stenting. J Am Coll Cardiol 2017 Apr 25; 69:2011. PMID: 28427576 http://www.sciencedirect.com/science/article/pii/S0735109717306964 - Rao SV, Harrington RA. Bleeding and mortality with dual antiplatelet therapy: The Rashomon effect. J Am Coll Cardiol 2017 Apr 25; 69:2023. PMID: 28427577 http://www.sciencedirect.com/science/article/pii/S0735109717360187
  15. Hilkens NA, Algra A, Kappelle LJ, et al. Early time course of major bleeding on antiplatelet therapy after TIA or ischemic stroke. Neurology 2018 Feb 20; 90:e683 PMID: 29374102 Free PMC Article http://n.neurology.org/content/90/8/e683
  16. Kedhi E, Fabris E, van der Ent M et al Six months versus 12 months dual antiplatelet therapy after drug-eluting stent implantation in ST-elevation myocardial infarction (DAPT-STEMI): randomised, multicentre, non-inferiority trial. BMJ 2018;363:k3793 PMID: 30279197 Free Article https://www.bmj.com/content/363/bmj.k3793
  17. 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/American Heart Association Task Force on Clinical Practice Guidelines. J Thorac Cardiovasc Surg. 2016 Nov;152(5):1243-1275. PMID: 27751237
  18. Watanabe H, Domei R, 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;321(24):2414-2427. PMID: 31237644 https://jamanetwork.com/journals/jama/fullarticle/2736563 - Hahn JH, Song YB, Oh JH 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;321(24):2428-2437 PMID: 31237645 https://jamanetwork.com/journals/jama/fullarticle/2736564 - Ziada KM, Moliterno DJ. Dual Antiplatelet TherapyIs It Time to Cut the Cord With Aspirin? JAMA. 2019;321(24):2409-2411 PMID: 31237621 https://jamanetwork.com/journals/jama/fullarticle/2736537
  19. Yin SHL, Xu P, Wang B et al Duration of dual antiplatelet therapy after percutaneous coronary intervention with drug-eluting stent: systematic review and network meta-analysis. BMJ 2019;365:l2222 PMID: 31253632 Free Article https://www.bmj.com/content/365/bmj.l2222
  20. Steg PG, Bhatt DL, Simon T et al. Ticagrelor in patients with stable coronary disease and diabetes. N Engl J Med 2019 Sep 1; PMID: 31475798 https://www.nejm.org/doi/10.1056/NEJMoa1908077
  21. Medical Knowledge Self Assessment Program (MKSAP) 19 American College of Physicians, Philadelphia 2022
  22. Gao Y, Chen W, Pan Y, et al. Dual Antiplatelet Treatment up to 72 Hours after Ischemic Stroke. N Engl J Med. 2023 Dec 28;389(26):2413-2424. PMID: 38157499 https://www.nejm.org/doi/10.1056/NEJMoa2309137
  23. Swift Yasgur B Low LDL With DAPT Tied to High Bleeding Risk After Stroke. Medscape. March 21, 2024 https://www.medscape.com/viewarticle/low-ldl-dapt-tied-high-bleeding-risk-after-stroke-2024a10005a3 - Cheng A, Xue J, Wang A et al LDL-C Levels and Bleeding Risk in Patients Taking DAPT After Minor Ischemic Stroke or TIA. JAMA Neurol. 2024;81(4):354-362. PMID: 38436990 PMCID: PMC10913006 (available on 2025-03-04) https://jamanetwork.com/journals/jamaneurology/fullarticle/2815831
  24. Guan L, Han S, Johnston SC et al Duration of Benefit and Risk of Dual Antiplatelet Therapy up to 72 Hours After Mild Ischemic Stroke and Transient Ischemic Attack. Neurology. 2024 Oct 8;103(7):e209845. PMID: 39270151 Clinical Trial.